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Sample records for cognate immunity factor

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-10-01

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

  2. The effect of aging on cognate function and development of immune memory

    OpenAIRE

    Haynes, Laura

    2005-01-01

    Immunological memory is one of the central features of the immune system and can be described as the ability of the immune system to respond more efficiently to a second encounter with the same pathogen. The immune system is dramatically affected by age-related changes and it is becoming apparent that immune memory exhibits significant defects as a result of aging. Although immune memory generated during youth functions well into old age, that generated later in life functions poorly. Importa...

  3. Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome

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    Song Hongshuo

    2012-10-01

    Full Text Available Abstract Background A modest change in HIV-1 fitness can have a significant impact on viral quasispecies evolution and viral pathogenesis, transmission and disease progression. To determine the impact of immune escape mutations selected by cytotoxic T lymphocytes (CTL on viral fitness in the context of the cognate transmitted/founder (T/F genome, we developed a new competitive fitness assay using molecular clones of T/F genomes lacking exogenous genetic markers and a highly sensitive and precise parallel allele-specific sequencing (PASS method. Results The T/F and mutant viruses were competed in CD4+ T-cell enriched cultures, relative proportions of viruses were assayed after repeated cell-free passage, and fitness costs were estimated by mathematical modeling. Naturally occurring HLA B57-restricted mutations involving the TW10 epitope in Gag and two epitopes in Tat/Rev and Env were assessed independently and together. Compensatory mutations which restored viral replication fitness were also assessed. A principal TW10 escape mutation, T242N, led to a 42% reduction in replication fitness but V247I and G248A mutations in the same epitope restored fitness to wild-type levels. No fitness difference was observed between the T/F and a naturally selected variant carrying the early CTL escape mutation (R355K in Env and a reversion mutation in the Tat/Rev overlapping region. Conclusions These findings reveal a broad spectrum of fitness costs to CTL escape mutations in T/F viral genomes, similar to recent findings reported for neutralizing antibody escape mutations, and highlight the extraordinary plasticity and adaptive potential of the HIV-1 genome. Analysis of T/F genomes and their evolved progeny is a powerful approach for assessing the impact of composite mutational events on viral fitness.

  4. Divergence of primary cognate B- and T-cell proliferative responses to subcutaneous and intravenous immunization with virus-like particles.

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    Temchura, Vladimir; Kalinin, Svetlana; Nabi, Ghulam; Tippler, Bettina; Niezold, Thomas; Uberla, Klaus

    2014-08-22

    A major advantage of virus-like particle (VLP) vaccines against HIV is their structural identity to wild-type viruses, ensuring that antigen-specific B-cells encounter the envelope protein in its natural conformation. For the induction of affinity-matured antibodies, the B-cells must also obtain help from T-cells that are restricted by linear epitopes. Using B- and T-cell transgenic mouse models, we compared the efficacy of modified HIV-VLPs delivered by subcutaneous and intravenous immunization to stimulate primary B- and T-cell proliferative responses in different lymphoid organs. VLPs containing an influenza virus hemagglutinin epitope within the HIV-Gag protein induced comparable primary cognate T-cell proliferative responses in the draining lymph node and the spleen, irrespective of the delivery route. In contrast, after subcutaneous immunization with HIV-Gag VLPs containing hen egg lysozyme (HEL) on their surface, the proliferative response of transgenic HEL-specific B-cells was restricted to the draining lymph nodes, while intravenous VLP immunization primarily induced a B-cell proliferative response in the spleen. In vitro co-culture experiments further revealed that the presentation of VLP-associated surface antigens by dendritic cells to cognate B-cells is inefficient. This is consistent with a direct triggering of the B-cell proliferative response by the VLPs and suggests that HIV VLPs may indeed be suitable to directly promote the expansion of B-cells specific for conformational epitopes that are unique to functionally-active Env spikes on the virion. Further investigations are warranted to explore potential differences in the quality and protective potency of HIV-specific antibody responses induced by the two routes.

  5. Expression patterns of two heat-shock cognate 70 genes during immune responses and larval development of the Chinese mitten crab Eriocheir sinensis.

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    Li, P; Jiang, X F; Guo, W B; Yan, J; Zhou, K Y

    2016-09-16

    Two heat-shock protein (HSP) 70 family transcripts, heat-shock protein 70 cognate 5 and heat-shock protein 70 cognate 3 (designated as EsHSC70-5 and EsHSC70-3, respectively), were isolated from the Chinese mitten crab Eriocheir sinensis and their expression profiles were evaluated for their responsiveness to larval development and immune challenge in adult crabs. The HSPs exhibited 45-89% identity with other heat-shock proteins, and they shared similar structural features. EsHSC70 mRNA expression was detected not only during infection but also during the developmental larval stages. The EsHSC70s were enriched, and their expression fluctuated during early development. EsHSC70 mRNA expression was significantly induced by Vibrio parahaemolyticus challenge in all of the tissues studied (P < 0.05). Expression of EsHSC70 mRNA in the hepatopancreas and at the early zoeal stages was particularly pronounced, and the two EsHSC70s exhibited differential expression patterns both chronologically and spatially. The EsHSC70-5 mRNA level was significantly downregulated in the intestine and gills compared to that in controls at nearly all time points, and was expressed at a lower level after the bacterial challenge, indicating that EsHSC70-5 and EsHSC70-3 respond to immune challenges. The stage-specific enrichment of EsHSC70 transcripts in crabs suggests that these stress proteins play an essential role during brachyurization events.

  6. English-French Cognate Dictionary.

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    Hammer, Petra; Monod, Madeleine

    This dictionary contains a word list of 10,993 English-French cognates (words with the same or similar spelling and meaning in both languages), including some loan words from other languages. A systematic review of the Larousse "Dictionnaire Moderne Francais--Anglais" (1960) provided this list of cognates. Deceptive cognates, or words…

  7. HIF transcription factors, inflammation, and immunity.

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    Palazon, Asis; Goldrath, Ananda W; Nizet, Victor; Johnson, Randall S

    2014-10-16

    The hypoxic response in cells and tissues is mediated by the family of hypoxia-inducible factor (HIF) transcription factors; these play an integral role in the metabolic changes that drive cellular adaptation to low oxygen availability. HIF expression and stabilization in immune cells can be triggered by hypoxia, but also by other factors associated with pathological stress: e.g., inflammation, infectious microorganisms, and cancer. HIF induces a number of aspects of host immune function, from boosting phagocyte microbicidal capacity to driving T cell differentiation and cytotoxic activity. Cellular metabolism is emerging as a key regulator of immunity, and it constitutes another layer of fine-tuned immune control by HIF that can dictate myeloid cell and lymphocyte development, fate, and function. Here we discuss how oxygen sensing in the immune microenvironment shapes immunological response and examine how HIF and the hypoxia pathway control innate and adaptive immunity.

  8. Structures of the Ultra-High-Affinity Protein-Protein Complexes of Pyocins S2 and AP41 and Their Cognate Immunity Proteins from Pseudomonas aeruginosa.

    Science.gov (United States)

    Joshi, Amar; Grinter, Rhys; Josts, Inokentijs; Chen, Sabrina; Wojdyla, Justyna A; Lowe, Edward D; Kaminska, Renata; Sharp, Connor; McCaughey, Laura; Roszak, Aleksander W; Cogdell, Richard J; Byron, Olwyn; Walker, Daniel; Kleanthous, Colin

    2015-08-28

    How ultra-high-affinity protein-protein interactions retain high specificity is still poorly understood. The interaction between colicin DNase domains and their inhibitory immunity (Im) proteins is an ultra-high-affinity interaction that is essential for the neutralisation of endogenous DNase catalytic activity and for protection against exogenous DNase bacteriocins. The colicin DNase-Im interaction is a model system for the study of high-affinity protein-protein interactions. However, despite the fact that closely related colicin-like bacteriocins are widely produced by Gram-negative bacteria, this interaction has only been studied using colicins from Escherichia coli. In this work, we present the first crystal structures of two pyocin DNase-Im complexes from Pseudomonas aeruginosa, pyocin S2 DNase-ImS2 and pyocin AP41 DNase-ImAP41. These structures represent divergent DNase-Im subfamilies and are important in extending our understanding of protein-protein interactions for this important class of high-affinity protein complex. A key finding of this work is that mutations within the immunity protein binding energy hotspot, helix III, are tolerated by complementary substitutions at the DNase-Immunity protein binding interface. Im helix III is strictly conserved in colicins where an Asp forms polar interactions with the DNase backbone. ImAP41 contains an Asp-to-Gly substitution in helix III and our structures show the role of a co-evolved substitution where Pro in DNase loop 4 occupies the volume vacated and removes the unfulfilled hydrogen bond. We observe the co-evolved mutations in other DNase-Immunity pairs that appear to underpin the split of this family into two distinct groups.

  9. Structures of the ultra-high-affinity protein–protein complexes of pyocins S2 and AP41 and their cognate immunity proteins from pseudomonas aeruginosa

    OpenAIRE

    Joshi, Amar; Grinter, Rhys; Josts, Inokentijs; Chen, Sabrina; Wojdyla, Justyna; Lowe, Edward; Kaminska, Renata; Sharp, Connor; McCaughey, Laura; Roszak, Aleksander; Cogdell, Richard; Byron, Olwyn; Walker, Daniel; Kleanthous, Colin

    2015-01-01

    How ultra-high-affinity protein–protein interactions retain high specificity is still poorly understood. The interaction between colicin DNase domains and their inhibitory immunity (Im) proteins is an ultra-high-affinity interaction that is essential for the neutralisation of endogenous DNase catalytic activity and for protection against exogenous DNase bacteriocins. The colicin DNase–Im interaction is a model system for the study of high-affinity protein–protein interactions. However, despit...

  10. Structures of the Ultra-High-Affinity Protein–Protein Complexes of Pyocins S2 and AP41 and Their Cognate Immunity Proteins from Pseudomonas aeruginosa

    Science.gov (United States)

    Joshi, Amar; Grinter, Rhys; Josts, Inokentijs; Chen, Sabrina; Wojdyla, Justyna A.; Lowe, Edward D.; Kaminska, Renata; Sharp, Connor; McCaughey, Laura; Roszak, Aleksander W.; Cogdell, Richard J.; Byron, Olwyn; Walker, Daniel; Kleanthous, Colin

    2015-01-01

    How ultra-high-affinity protein–protein interactions retain high specificity is still poorly understood. The interaction between colicin DNase domains and their inhibitory immunity (Im) proteins is an ultra-high-affinity interaction that is essential for the neutralisation of endogenous DNase catalytic activity and for protection against exogenous DNase bacteriocins. The colicin DNase–Im interaction is a model system for the study of high-affinity protein–protein interactions. However, despite the fact that closely related colicin-like bacteriocins are widely produced by Gram-negative bacteria, this interaction has only been studied using colicins from Escherichia coli. In this work, we present the first crystal structures of two pyocin DNase–Im complexes from Pseudomonas aeruginosa, pyocin S2 DNase–ImS2 and pyocin AP41 DNase–ImAP41. These structures represent divergent DNase–Im subfamilies and are important in extending our understanding of protein–protein interactions for this important class of high-affinity protein complex. A key finding of this work is that mutations within the immunity protein binding energy hotspot, helix III, are tolerated by complementary substitutions at the DNase–Immunity protein binding interface. Im helix III is strictly conserved in colicins where an Asp forms polar interactions with the DNase backbone. ImAP41 contains an Asp-to-Gly substitution in helix III and our structures show the role of a co-evolved substitution where Pro in DNase loop 4 occupies the volume vacated and removes the unfulfilled hydrogen bond. We observe the co-evolved mutations in other DNase–Immunity pairs that appear to underpin the split of this family into two distinct groups. PMID:26215615

  11. COGNATE: comparative gene annotation characterizer.

    Science.gov (United States)

    Wilbrandt, Jeanne; Misof, Bernhard; Niehuis, Oliver

    2017-07-17

    The comparison of gene and genome structures across species has the potential to reveal major trends of genome evolution. However, such a comparative approach is currently hampered by a lack of standardization (e.g., Elliott TA, Gregory TR, Philos Trans Royal Soc B: Biol Sci 370:20140331, 2015). For example, testing the hypothesis that the total amount of coding sequences is a reliable measure of potential proteome diversity (Wang M, Kurland CG, Caetano-Anollés G, PNAS 108:11954, 2011) requires the application of standardized definitions of coding sequence and genes to create both comparable and comprehensive data sets and corresponding summary statistics. However, such standard definitions either do not exist or are not consistently applied. These circumstances call for a standard at the descriptive level using a minimum of parameters as well as an undeviating use of standardized terms, and for software that infers the required data under these strict definitions. The acquisition of a comprehensive, descriptive, and standardized set of parameters and summary statistics for genome publications and further analyses can thus greatly benefit from the availability of an easy to use standard tool. We developed a new open-source command-line tool, COGNATE (Comparative Gene Annotation Characterizer), which uses a given genome assembly and its annotation of protein-coding genes for a detailed description of the respective gene and genome structure parameters. Additionally, we revised the standard definitions of gene and genome structures and provide the definitions used by COGNATE as a working draft suggestion for further reference. Complete parameter lists and summary statistics are inferred using this set of definitions to allow down-stream analyses and to provide an overview of the genome and gene repertoire characteristics. COGNATE is written in Perl and freely available at the ZFMK homepage ( https://www.zfmk.de/en/COGNATE ) and on github ( https://github.com/ZFMK/COGNATE

  12. Characterization and in vivo regulon determination of an ECF sigma factor and its cognate anti-sigma factor in Nostoc punctiforme.

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    Bell, Nicole; Lee, Jamie J; Summers, Michael L

    2017-04-01

    Based on primary sequence comparisons and genomic context, Npun_F4153 (SigG)/Npun_F4154 (SapG) of the cyanobacterium Nostoc punctiforme were hypothesized to encode an ECF sigma factor/anti-sigma factor pair. Transcription of sigG increased in heterocysts and akinetes, and after EDTA treatment. Interaction between SigG and the predicted cytoplasmic domain of SapG was observed in vitro. A SigG-GFP translational fusion protein localized to the periphery of vegetative cells in vivo, but lost this association following heat stress. A sigG mutant was unable to survive envelope damage caused by heat or EDTA, but was able to form functional heterocysts. Akinetes in the mutant strain appeared normal, but these cultures were less resistant to lysozyme and cold treatments than those of the wild-type strain. The SigG in vivo regulon was determined before and during akinete differentiation using DNA microarray analysis, and found to include multiple genes with putative association to the cell envelope. Mapped promoters common to both arrays enabled identification of a SigG promoter-binding motif that was supported in vivo by reporter studies, and in vitro by run-off transcription experiments. These findings support SigG/SapG as a sigma/anti-sigma pair involved in repair of envelope damage resulting from exogenous sources or cellular differentiation. © 2017 John Wiley & Sons Ltd.

  13. An extracytoplasmic function sigma factor cotranscribed with its cognate anti-sigma factor confers tolerance to NaCl, ethanol and methylene blue in Azospirillum brasilense Sp7.

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    Mishra, Mukti Nath; Kumar, Santosh; Gupta, Namrata; Kaur, Simarjot; Gupta, Ankush; Tripathi, Anil K

    2011-04-01

    Azospirillum brasilense, a plant-growth-promoting rhizobacterium, is exposed to changes in its abiotic environment, including fluctuations in temperature, salinity, osmolarity, oxygen concentration and nutrient concentration, in the rhizosphere and in the soil. Since extra-cytoplasmic function (ECF) sigma factors play an important role in stress adaptation, we analysed the role of ECF sigma factor (also known as RpoE or σ(E)) in abiotic stress tolerance in A. brasilense. An in-frame rpoE deletion mutant of A. brasilense Sp7 was carotenoidless and slow-growing, and was sensitive to salt, ethanol and methylene blue stress. Expression of rpoE in the rpoE deletion mutant complemented the defects in growth, carotenoid biosynthesis and sensitivity to different stresses. Based on data from reverse transcriptase-PCR, a two-hybrid assay and a pull-down assay, we present evidence that rpoE is cotranscribed with chrR and the proteins synthesized from these two overlapping genes interact with each other. Identification of the transcription start site by 5' rapid amplification of cDNA ends showed that the rpoE-chrR operon was transcribed by two promoters. The proximal promoter was less active than the distal promoter, whose consensus sequence was characteristic of RpoE-dependent promoters found in alphaproteobacteria. Whereas the proximal promoter was RpoE-independent and constitutively expressed, the distal promoter was RpoE-dependent and strongly induced in response to stationary phase and elevated levels of ethanol, salt, heat and methylene blue. This study shows the involvement of RpoE in controlling carotenoid synthesis as well as in tolerance to some abiotic stresses in A. brasilense, which might be critical in the adaptation, survival and proliferation of this rhizobacterium in the soil and rhizosphere under stressful conditions.

  14. Brucella spp. Virulence Factors and Immunity.

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    Byndloss, Mariana X; Tsolis, Renee M

    2016-01-01

    Brucellosis, caused by bacteria of the genus Brucella, is an important zoonotic infection that causes reproductive disease in domestic animals and chronic debilitating disease in humans. An intriguing aspect of Brucella infection is the ability of these bacteria to evade the host immune response, leading to pathogen persistence. Conversely, in the reproductive tract of infected animals, this stealthy pathogen is able to cause an acute severe inflammatory response. In this review, we discuss the different mechanisms used by Brucella to cause disease, with emphasis on its virulence factors and the dichotomy between chronic persistence and reproductive disease.

  15. 70-kDa Heat Shock Cognate Protein hsc70 Mediates Calmodulin-dependent Nuclear Import of the Sex-determining Factor SRY*

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    Kaur, Gurpreet; Lieu, Kim G.; Jans, David A.

    2013-01-01

    We recently showed that the developmentally important family of SOX (SRY (sex determining region on the Y chromosome)-related high mobility group (HMG) box) proteins require the calcium-binding protein calmodulin (CaM) for optimal nuclear accumulation, with clinical mutations in SRY that specifically impair nuclear accumulation via this pathway resulting in XY sex reversal. However, the mechanism by which CaM facilitates nuclear accumulation is unknown. Here, we show, for the first time, that the 70-kDa heat shock cognate protein hsc70 plays a key role in CaM-dependent nuclear import of SRY. Using a reconstituted nuclear import assay, we show that antibodies to hsc70 significantly reduce nuclear accumulation of wild type SRY and mutant derivatives thereof that retain CaM-dependent nuclear import, with an increased rate of nuclear accumulation upon addition of both CaM and hsc70, in contrast to an SRY mutant derivative with impaired CaM binding. siRNA knockdown of hsc70 in intact cells showed similar results, indicating clear dependence upon hsc70 for CaM-dependent nuclear import. Analysis using the technique of fluorescence recovery after photobleaching indicated that hsc70 is required for the maximal rate of SRY nuclear import in living cells but has no impact upon SRY nuclear retention/nuclear dynamics. Finally, we demonstrate direct binding of hsc70 to the SRY·CaM complex, with immunoprecipitation experiments from cell extracts showing association of hsc70 with wild type SRY, but not with a mutant derivative with impaired CaM binding, dependent on Ca2+. Our novel findings strongly implicate hsc70 in CaM-dependent nuclear import of SRY. PMID:23235156

  16. Socio- Demographic Factors And Non- Immunization In Children

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    Singh H

    1992-01-01

    Full Text Available An Investigation was conducted to evaluate various socio- demographic variables and non- immunization in children of this region. Among all the children brought to well baby clinics, 20% were not immunized against any of the six killer diseases. Eighty two percent these were from social class I and II. Mothers of 50% and fathers of 40% non â€" immunized children were illiterate. Common factors for non- immunization were illness, ignorance and indifference.

  17. All-atom structural models for complexes of insulin-like growth factors IGF1 and IGF2 with their cognate receptor.

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    Vashisth, Harish; Abrams, Cameron F

    2010-07-16

    Type 1 insulin-like growth factor receptor (IGF1R) is a membrane-spanning glycoprotein of the insulin receptor family that has been implicated in a variety of cancers. The key questions related to molecular mechanisms governing ligand recognition by IGF1R remain unanswered, partly due to the lack of testable structural models of apo or ligand-bound receptor complexes. Using a homology model of the IGF1R ectodomain IGF1RDeltabeta, we present the first experimentally consistent all-atom structural models of IGF1/IGF1RDeltabeta and IGF2/IGF1RDeltabeta complexes. Our explicit-solvent molecular dynamics (MD) simulation of apo-IGF1RDeltabeta shows that it displays asymmetric flexibility mechanisms that result in one of two binding pockets accessible to growth factors IGF1 and IGF2, as demonstrated via an MD-assisted Monte Carlo docking procedure. Our MD-generated ensemble of structures of apo and IGF1-bound IGF1RDeltabeta agrees reasonably well with published small-angle X-ray scattering data. We observe simultaneous contacts of each growth factor with sites 1 and 2 of IGF1R, suggesting cross-linking of receptor subunits. Our models provide direct evidence in favor of suggested electrostatic complementarity between the C-domain (IGF1) and the cysteine-rich domain (IGF1R). Our IGF1/IGF1RDeltabeta model provides structural bases for the observation that a single IGF1 molecule binds to IGF1RDeltabeta at low concentrations in small-angle X-ray scattering studies. We also suggest new possible structural bases for differences in the affinities of insulin, IGF1, and IGF2 for their noncognate receptors.

  18. Foreign language comprehension achievement: insights from the cognate facilitation effect

    OpenAIRE

    Casaponsa, Aina; Antón, Eneko; Pérez, Alejandro; Duñabeitia, Jon A.

    2015-01-01

    Numerous studies have shown that the native language influences foreign word recognition and that this influence is modulated by the proficiency in the non-native language. Here we explored how the degree of reliance on cross-language similarity (as measured by the cognate facilitation effect) together with other domain-general cognitive factors contribute to reading comprehension achievement in a non-native language at different stages of the learning process. We tested two groups of native ...

  19. Complement factor H in host defense and immune evasion.

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    Parente, Raffaella; Clark, Simon J; Inforzato, Antonio; Day, Anthony J

    2017-05-01

    Complement is the major humoral component of the innate immune system. It recognizes pathogen- and damage-associated molecular patterns, and initiates the immune response in coordination with innate and adaptive immunity. When activated, the complement system unleashes powerful cytotoxic and inflammatory mechanisms, and thus its tight control is crucial to prevent damage to host tissues and allow restoration of immune homeostasis. Factor H is the major soluble inhibitor of complement, where its binding to self markers (i.e., particular glycan structures) prevents complement activation and amplification on host surfaces. Not surprisingly, mutations and polymorphisms that affect recognition of self by factor H are associated with diseases of complement dysregulation, such as age-related macular degeneration and atypical haemolytic uremic syndrome. In addition, pathogens (i.e., non-self) and cancer cells (i.e., altered-self) can hijack factor H to evade the immune response. Here we review recent (and not so recent) literature on the structure and function of factor H, including the emerging roles of this protein in the pathophysiology of infectious diseases and cancer.

  20. Cellular factors targeting APCs to modulate adaptive T cell immunity.

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    Visperas, Anabelle; Do, Jeongsu; Min, Booki

    2014-01-01

    The fate of adaptive T cell immunity is determined by multiple cellular and molecular factors, among which the cytokine milieu plays the most important role in this process. Depending on the cytokines present during the initial T cell activation, T cells become effector cells that produce different effector molecules and execute adaptive immune functions. Studies thus far have primarily focused on defining how these factors control T cell differentiation by targeting T cells themselves. However, other non-T cells, particularly APCs, also express receptors for the factors and are capable of responding to them. In this review, we will discuss how APCs, by responding to those cytokines, influence T cell differentiation and adaptive immunity.

  1. Cellular Factors Targeting APCs to Modulate Adaptive T Cell Immunity

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    Anabelle Visperas

    2014-01-01

    Full Text Available The fate of adaptive T cell immunity is determined by multiple cellular and molecular factors, among which the cytokine milieu plays the most important role in this process. Depending on the cytokines present during the initial T cell activation, T cells become effector cells that produce different effector molecules and execute adaptive immune functions. Studies thus far have primarily focused on defining how these factors control T cell differentiation by targeting T cells themselves. However, other non-T cells, particularly APCs, also express receptors for the factors and are capable of responding to them. In this review, we will discuss how APCs, by responding to those cytokines, influence T cell differentiation and adaptive immunity.

  2. 中日同形近义词的产出难易度及其影响因素%Factors that Influence the Difficulty of Chinese Learners’Output of Japanese-Chinese Partially Deceptive Cognates

    Institute of Scientific and Technical Information of China (English)

    庄倩

    2014-01-01

    日语词汇中的“中日同形近义词”被认为是中国日语学习者日语表达时误用较多、难以习得的一类词,但是目前却缺乏对其难度成因进行深度剖析的实证研究。本研究从词汇的特征出发,假设母语与目标语词义差异的类型、母语与目标语在词性上的差异以及目标语本身的难易度差异三个因素影响学习者的产出结果,并通过统计中国高校日语专业35名学生产出测试的得分,验证了假设因素的存在。本研究有益于帮助教师更为全面地了解学习者产出中日同形近义词的状况及成因,在教学活动中有针对性地提高学习者的学习效能。%“Partially Deceptive Cognates”in Japanese, which share the same orthography but partly different meanings with their Chinese counterparts, are considered very difficult for Chinese learners of the Japanese language. However, there have been no adequate empirical studies on the causes for such difficulty. Based on the features of vocabulary, the present study proposes the hypotheses that the following factors affect learners’production:differences between L1 and L2 in vocabulary meaning, parts of speech, and levels of difficulty. The study verifies the existence and influence of the hypothetical factors with empirical evidence from a production test taken by 35 Japanese majors from a Chinese university. It may prove beneficial for teachers to have an overall perspective on the situation and causes of the learners’production of partially deceptive cognates in order to improve their efficiency in teaching activities.

  3. Cognate facilitation effects in trilingual word recognition

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    Weronika Szubko-Sitarek

    2011-08-01

    Full Text Available Research on bilingual word recognition suggests that lexical access is nonselective with respect to language, i.e., that word representations of both languages become active during recognition. One piece of evidence supporting nonselective access is that bilinguals recognize cognates (words that are identical or similar in form and meaning in two or more languages faster than noncognates. In fact, any difference between how cognates and ‘monolingual’ words are processed by multilinguals would indicate that the other, currently irrelevant language must have played a role as well, at least as long as the two groups of words are comparable with respect to all dimensions other than language membership. The aim of the present paper is to report on two visual perceptual experiments conducted within the lexical decision task paradigm whose aim was to test the assumptions concerning the special position of cognates (the cognate facilitation effect, cf. Dijkstra, 2005 within a trilingual mind and to answer the question whether trilinguals rely upon their second language lexical knowledge when recognizing L3 words. The results of the experiments attest to simultaneous activation and parallel processing as well as interaction among all the three languages. At the same time, they point to the fact that cross-linguistic lexical access and the source and strength of transfer may be constrained by variables such task demands.

  4. Immune dysregulation in offspring of a bipolar parent. Altered serum levels of immune growth factors at adolescent age

    NARCIS (Netherlands)

    Snijders, J.G.; Mesman, E.; de Wit, H.; Wijkhuijs, AJM; Nolen, W. A.; Drexhage, H. A.; Hillegers, M. H. J.

    Immune dysregulation plays a role in the vulnerability for mood disorders. Immune growth factors, such as Stem Cell Factor (SCF), Insulin-like Growth Factor-Binding Protein-2 (IGF-BP2), Epidermal Growth Factor (EGF), IL-7 and sCD25 have repeatedly been reported altered in patients with mood

  5. English and Persian Cognates/Pseudo Cognates-A Cross-Linguistic Investigation

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    Amin Marzban

    2015-03-01

    Full Text Available Different world languages have a lot of contact with each other and have had different influences on one another. Cognates, words which are similar across two or more languages in some aspects, especially with regard to pronunciation, portray an interesting and relevant aspect of foreign/second language translation and research. This study intended to identify a type of cognate words called false cognates in Persian and English, words which have the same form in two languages but represent different meanings, and tried to study and determine the historical relations between English and Persian words. It also aimed to trace their route back from Proto Indo-European languages to the modern languages. To this end, the related literature was gone through and a sufficient corpus of information has been revealed. Afterwards, authentic monolingual dictionaries in both Farsi and English languages were consulted to provide definitions for the cognates and allow for their cross-linguistic comparison. The findings revealed that most of such problematic cognates with different meanings in Farsi and English as found through this study are likely to be confusing and deceptive for Farsi-speaking EFL learners. The findings also pointed to the need for this line of research to receive more scholarly attention. The study of true and false cognates has some implications for contrastive analysts, error analysts, translators, translation theorists, foreign language teachers, curriculum designers, as well as lexicographers and lexicologists.

  6. Micro Aerial Vehicle (MAV Flapping Motion Control Using an Immune Network with Different Immune Factors

    Directory of Open Access Journals (Sweden)

    Liguo Weng

    2013-08-01

    Full Text Available This paper proposes a novel Neural‐Immunology/Memory Network to address the problem of motion control for flapping‐wing Micro Aerial Vehicles (MAVs. This network is inspired by the human memory system as well as the immune system, and it is effective in attenuating the system errors and other lumped system uncertainties. In contrast to most existing Neural Networks, the convergence of this proposed Neural‐Immunology/Memory Network can be theoretically proven. Both analyses and simulations that are based on different immune factors show that the proposed control method is effective in dealing with external disturbances, system nonlinearities, uncertainties and parameter variations.

  7. Using Cognates to Scaffold Context Clue Strategies for Latino ELs

    Science.gov (United States)

    Montelongo, Jose A.; Hernandez, Anita C.; Herter, Roberta J.; Cuello, Jaime

    2011-01-01

    Latino English learners (ELs) come to elementary classrooms with many English-Spanish cognates in their listening, speaking, reading, and writing vocabularies. Cognates are words that are orthographically, semantically, and syntactically similar in two languages because of a shared etymology. Some cognates are identical in both English and…

  8. Using Cognates to Scaffold Context Clue Strategies for Latino ELs

    Science.gov (United States)

    Montelongo, Jose A.; Hernandez, Anita C.; Herter, Roberta J.; Cuello, Jaime

    2011-01-01

    Latino English learners (ELs) come to elementary classrooms with many English-Spanish cognates in their listening, speaking, reading, and writing vocabularies. Cognates are words that are orthographically, semantically, and syntactically similar in two languages because of a shared etymology. Some cognates are identical in both English and…

  9. [ROLE OF INNATE IMMUNITY FACTORS IN PERIODONTITIS PATHOGENESIS].

    Science.gov (United States)

    Gankovskaya, L V; Khelminskaya, N M; Molchanova, E A; Svitich, O A

    2016-01-01

    Chronic generalized periodontitis (CGP) is a disease of periodontium tissues supporting tooth induced by bacteria, that is characterized by the presence of processes of inflammation with destruction of bone tissue. The knowledge of molecular mechanisms of CGP pathogenesis facilitates creation of the most effective methods of therapy of this disease. Bacterial infection is a primary factor in periodontitis etiology, however is not sufficient for its start and subsequent development. It is known, that bacterial factors induce alocal inflammationreaction and.activate the system of innate immunity through activation of Toll-like receptors (TLR), located on the surface of resident cells and leukocytes. Activation of these cells results in production of pro-inflammatory cytokines and recruitment of phagocytes and lymphocytes into the inflammation zone. In review we examined the known data regarding factors of immune protection of periodontium including cell populations and cytokines, as well as mechanisms of tissue destruction, that support the tooth. Perspectives of therapy are also discussed

  10. Cognate costs in bilingual speech production: Evidence from language switching

    Directory of Open Access Journals (Sweden)

    Mirjam Broersma

    2016-09-01

    Full Text Available This study investigates cross-language lexical competition in the bilingual mental lexicon. It provides evidence for the occurrence of inhibition as well as the commonly reported facilitation during the production of cognates (words with similar phonological form and meaning in two languages in a mixed picture naming task by highly proficient Welsh-English bilinguals. Previous studies have typically found cognate facilitation. It has previously been proposed (with respect to non-cognates that cross-language inhibition is limited to low-proficient bilinguals; therefore, we tested highly proficient, early bilinguals. In a mixed naming experiment (i.e., picture naming with language switching, 48 highly proficient, early Welsh-English bilinguals named pictures in Welsh and English, including cognate and non-cognate targets. Participants were English-dominant, Welsh-dominant, or had equal language dominance. The results showed evidence for cognate inhibition in to ways. First, both facilitation and inhibition were found on the cognate trials themselves, compared to non-cognate controls, modulated by the participants’ language dominance. The English-dominant group showed cognate inhibition when naming in Welsh (and no difference between cognates and controls when naming in English, and the Welsh-dominant and equal dominance groups generally showed cognate facilitation. Second, cognate inhibition was found as a behavioral adaptation effect, with slower naming for non-cognate filler words in trials after cognates than after non-cognate controls. This effect was consistent across all language dominance groups and both target languages, suggesting that cognate production involved cognitive control even if this was not measurable in the cognate trials themselves. Finally, the results replicated patterns of symmetrical switch costs, as commonly reported for balanced bilinguals. We propose that cognate processing might be affected by two different

  11. Cognate Costs in Bilingual Speech Production: Evidence from Language Switching

    Science.gov (United States)

    Broersma, Mirjam; Carter, Diana; Acheson, Daniel J.

    2016-01-01

    This study investigates cross-language lexical competition in the bilingual mental lexicon. It provides evidence for the occurrence of inhibition as well as the commonly reported facilitation during the production of cognates (words with similar phonological form and meaning in two languages) in a mixed picture naming task by highly proficient Welsh-English bilinguals. Previous studies have typically found cognate facilitation. It has previously been proposed (with respect to non-cognates) that cross-language inhibition is limited to low-proficient bilinguals; therefore, we tested highly proficient, early bilinguals. In a mixed naming experiment (i.e., picture naming with language switching), 48 highly proficient, early Welsh-English bilinguals named pictures in Welsh and English, including cognate and non-cognate targets. Participants were English-dominant, Welsh-dominant, or had equal language dominance. The results showed evidence for cognate inhibition in two ways. First, both facilitation and inhibition were found on the cognate trials themselves, compared to non-cognate controls, modulated by the participants' language dominance. The English-dominant group showed cognate inhibition when naming in Welsh (and no difference between cognates and controls when naming in English), and the Welsh-dominant and equal dominance groups generally showed cognate facilitation. Second, cognate inhibition was found as a behavioral adaptation effect, with slower naming for non-cognate filler words in trials after cognates than after non-cognate controls. This effect was consistent across all language dominance groups and both target languages, suggesting that cognate production involved cognitive control even if this was not measurable in the cognate trials themselves. Finally, the results replicated patterns of symmetrical switch costs, as commonly reported for balanced bilinguals. We propose that cognate processing might be affected by two different processes, namely

  12. Targeting of the tumor necrosis factor receptor superfamily for cancer immunotherapy

    NARCIS (Netherlands)

    Bremer, Edwin

    2013-01-01

    The tumor necrosis factor (TNF) ligand and cognate TNF receptor superfamilies constitute an important regulatory axis that is pivotal for immune homeostasis and correct execution of immune responses. TNF ligands and receptors are involved in diverse biological processes ranging from the selective in

  13. Predicting growth in English and French vocabulary: The facilitating effects of morphological and cognate awareness.

    Science.gov (United States)

    D'Angelo, Nadia; Hipfner-Boucher, Kathleen; Chen, Xi

    2017-07-01

    The present study investigated the contribution of morphological and cognate awareness to the development of English and French vocabulary knowledge among young minority and majority language children who were enrolled in a French immersion program. Participating children (n = 75) were assessed in English and French on measures of morphological awareness, cognate awareness, and vocabulary knowledge from Grades 1 to 3. Hierarchical linear modeling was used to investigate linear trends in English and French vocabulary growth for minority and majority language children and to identify metalinguistic contributions to Grade 1 and Grade 3 English and French vocabulary performance and rate of growth. Results demonstrated a similar pattern of prediction for both groups of children. English and French morphological awareness and French-English cognate awareness significantly predicted concurrent and longitudinal vocabulary development after controlling for nonverbal reasoning, phonological awareness, and word identification. The contributions of morphological awareness to English vocabulary and cognate awareness to French vocabulary strengthened between Grades 1 and 2. These findings highlight the emerging importance of morphological and cognate awareness in children's vocabulary development and suggest that these metalinguistic factors can serve to broaden the vocabulary repertoire of children who enter school with limited language proficiency. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. Orthographic transparency and morphology of Spanish-English Cognate adjectives.

    Science.gov (United States)

    Montelongo, José A; Hernández, Anita C; Herter, Roberta J; Hernández, Carissa

    2009-12-01

    The English and Spanish languages share over 20,000 cognates. Cognates are words that are orthographically, semantically, and syntactically similar in two languages. In 2009, Montelongo, Hernández, and Herter collected orthographic transparency ratings for over 2,000 Spanish-English cognate nouns and cognate adjectives drawn from the Juilland and Chang-Rodríguez' Frequency Dictionary of Spanish Words. The present analysis of the cognate adjectives in the Montelongo, et al. norms identified orthographic and morphological characteristics which affected ratings of cognate transparency. The analysis identified an initial-letter effect: the earlier an English word deviates from its Spanish equivalent, the lower it is rated. Similarly, the more orthographically similar an English suffix is to its Spanish suffix equivalent, the higher its rating.

  15. [Susceptible and resistant factors in neuro-immune disease].

    Science.gov (United States)

    Sato, Shinya; Kira, Jun-ichi

    2013-05-01

    Neuro-immune diseases (NIDs) are caused by a complex interaction between multiple genetic and environmental factors, both of which can have some impacts on susceptibility or resistance to each disease. Remarkable advance in genome technology made possible the effective screening of thousands of single nucleotide polymorphisms in thousands of samples. Additionally, epidemiological science, supported by microbiology, immunology and biochemistry, has revealed many possible environmental factors. Integrating genetic and environmental research data will pave the way to inform and personalize therapeutic decision-making in NIDs. This review aims to discuss susceptible and resistant factors that have attracted the most attention in the recent years, especially focusing on multiple sclerosis, which is one of the most common NIDs.

  16. Induction of Erythropoiesis by MHC-Mediated Cognate Interactions between B- and T-Cells.

    Science.gov (United States)

    Guha, A; Tuck, D P; Cone, R E; Dainiak, N

    1997-01-01

    We have previously shown that the expression of membrane burst-promoting activity (mBPA), an erythropoietic cytokine, by B-lymphocytes is augmented by the addition of allogeneic effector cells to the B-cells. Here, we have examined immune mechanisms involved in the induction/promotion of erythropoiesis as assessed by the capacity of autologous and allogeneic peripheral blood lymphocytes to augment burst-forming unit-erythroid (BFU-E) in normal human bone marrow cells in vitro. Preincubation of mBPA-expressing human B-cells with monoclonal antibodies to major histocompatibility complex (MHC) antigens, abrogated erythropoietic activity of both autologous and allogeneic lymphocytes, suggesting that MHC antigens play a role in regulating the expression of the erythroid growth factor. Inhibition of BFU-E proliferation was also evident when antibodies to MHC class-I or class-II antigens were added directly to marrow culture. Furthermore, addition of anti-CD4 antibody to the cultures of PBL and autologous target BM cells markedly reduced erythroid proliferation induced by PBL. By contrast, anti-CD8 and control (UPC-10) monoclonal antibodies had no effect. These results provide evidence that MHC-mediated cognate interactions between T- and B-lymphocytes may participate in the control of erythropoiesis, either directly or by modulating mBPA function.

  17. Towards a syntactic analysis of European Portuguese cognate objects

    Directory of Open Access Journals (Sweden)

    Celda Morgado Choupina

    2013-01-01

    Full Text Available The present paper aims at discussing selected syntactic aspects of cognate objects in European Portuguese, along the lines of Distributed Morphology (Haugen, 2009. Cognate objects may be readily discovered in numerous human languages, including European Portuguese (Chovia uma chuva miudinha. It is assumed in papers devoted to their English counterparts that they belong to various subclasses. Indeed, some of them are genuine cognates (to sleep a sleep... or hyponyms (to dance a jig; Hale & Keyser, 2002. It turns out that in European Portuguese, they can be split into four different categories: (i genuine cognate objects (chorar um choro..., (ii similar cognate objects (dançar uma dança (iii objects hyponyms (dançar um tango and (iv prepositional cognate objects (morrer de uma morte .... There are, then, significant differences between various classes of cognate objects: whereas the genuine ones call imperatively for a restrictive modifier and a definite article, the remaining ones admit it only optionally. It might be concluded, then, that a lexicalist theory set up along the lines of Hale and Keyser is unable to deal successfully with distributional facts proper to various classes of cognate constructions in European Portuguese. That is why the present study is conducted more in accordance with syntactic principles of Distributed Morphology, with a strong impact of hypotheses put forward by Haugen (2009.

  18. Foreign language comprehension achievement: insights from the cognate facilitation effect.

    Science.gov (United States)

    Casaponsa, Aina; Antón, Eneko; Pérez, Alejandro; Duñabeitia, Jon A

    2015-01-01

    Numerous studies have shown that the native language influences foreign word recognition and that this influence is modulated by the proficiency in the non-native language. Here we explored how the degree of reliance on cross-language similarity (as measured by the cognate facilitation effect) together with other domain-general cognitive factors contribute to reading comprehension achievement in a non-native language at different stages of the learning process. We tested two groups of native speakers of Spanish learning English at elementary and intermediate levels in an academic context. A regression model approach showed that domain-general cognitive skills are good predictors of second language reading achievement independently of the level of proficiency. Critically, we found that individual differences in the degree of reliance on the native language predicted foreign language reading achievement, showing a markedly different pattern between proficiency groups. At lower levels of proficiency the cognate facilitation effect was positively related with reading achievement, while this relation became negative at intermediate levels of foreign language learning. We conclude that the link between native- and foreign-language lexical representations helps participants at initial stages of the learning process, whereas it is no longer the case at intermediate levels of proficiency, when reliance on cross-language similarity is inversely related to successful non-native reading achievement. Thus, at intermediate levels of proficiency strong and direct mappings from the non-native lexical forms to semantic concepts are needed to achieve good non-native reading comprehension, in line with the premises of current models of bilingual lexico-semantic organization.

  19. Foreign language comprehension achievement: insights from the cognate facilitation effect

    Directory of Open Access Journals (Sweden)

    Aina eCasaponsa

    2015-05-01

    Full Text Available Numerous studies have shown that the native language influences foreign word recognition and that this influence is modulated by the proficiency in the nonnative language. Here we explored how the degree of reliance on cross-language similarity (as measured by the cognate facilitation effect together with other domain-general cognitive factors contribute to reading comprehension achievement in a nonnative language at different stages of the learning process. We tested two groups of native speakers of Spanish learning English at elementary and intermediate levels in an academic context. A regression model approach showed that domain-general cognitive skills are good predictors of second language reading achievement independently of the level of proficiency. Critically, we found that individual differences in the degree of reliance on the native language predicted foreign language reading achievement, showing a markedly different pattern between proficiency groups. At lower levels of proficiency the cognate facilitation effect was positively related with reading achievement, while this relation became negative at intermediate levels of foreign language learning. We conclude that the link between native- and foreign-language lexical representations helps participants at initial stages of the learning process, whereas it is no longer the case at intermediate levels of proficiency, when reliance on cross-language similarity is inversely related to successful nonnative reading achievement. Thus, at intermediate levels of proficiency strong and direct mappings from the nonnative lexical forms to semantic concepts are needed to achieve good nonnative reading comprehension, in line with the premises of current models of bilingual lexico-semantic organization.

  20. Dietary immunomodulatory factors in the development of immune tolerance.

    Science.gov (United States)

    West, Christina E; D'Vaz, Nina; Prescott, Susan L

    2011-08-01

    Emerging evidence suggests that exposures during pregnancy and the early postnatal period can modify gene expression and disease propensity. Diet is a major environmental exposure, and dietary factors, including polyunsaturated fatty acids, probiotics, oligosaccharides, antioxidants, folate, and other vitamins, have effects on immune function. Some also have been implicated in reduced risk of allergy in observational studies. Intervention trials with polyunsaturated fatty acids, probiotics, and oligosaccharides suggest preliminary but as-of-yet-unconfirmed benefits. Food allergen avoidance during pregnancy, lactation, or infancy has provided no consistent evidence in allergy prevention and is no longer recommended. Rather, there is now a focus on food allergens in tolerance induction. Specific nutrients can induce changes in gene expression during early development and have been implicated in potentially heritable "epigenetic" changes in disease predisposition. Collectively, these observations emphasize that early exposures may modify tolerance development and that further research on these exposures should remain a priority.

  1. Standardized ileal digestible lysine requirements of male pigs immunized against gonadotrophin releasing factor

    National Research Council Canada - National Science Library

    Moore, K L; Mullan, B P; Kim, J C; Dunshea, F R

    2016-01-01

    An experiment was conducted to determine the standardized ileal digestible (SID) Lys requirement of entire male and male pigs immunized against gonadotrophin releasing factor (GnRF; immunocastrates...

  2. Factors associated with incomplete childhood immunization in Arbegona district, southern Ethiopia: a case – control study

    OpenAIRE

    Negussie, Abel; Kassahun, Wondewosen; Assegid, Sahilu; Hagan, Ada K.

    2016-01-01

    Background The prevention of child mortality through immunization is one of the most cost-effective and widely applied public health interventions. In Ethiopia, the Expanded Program on Immunization (EPI) schedule is rarely completed as planned and the full immunization rate is only 24 %. The objective of this study was to identify determinant factors of incomplete childhood immunization in Arbegona district, Sidama zone, southern Ethiopia. Methods A community based unmatched case-control stud...

  3. Distributions of cognates in Europe as based on Levenshtein distance

    NARCIS (Netherlands)

    Schepens, J.J.; Dijkstra, A.F.J.; Grootjen, F.A.

    2012-01-01

    Researchers on bilingual processing can benefit from computational tools developed in artificial intelligence. We show that a normalized Levenshtein distance function can efficiently and reliably simulate bilingual orthographic similarity ratings. Orthographic similarity distributions of cognates

  4. Distributions of cognates in Europe as based on Levenshtein distance

    NARCIS (Netherlands)

    Schepens, J.J.; Dijkstra, A.F.J.; Grootjen, F.A.

    2012-01-01

    Researchers on bilingual processing can benefit from computational tools developed in artificial intelligence. We show that a normalized Levenshtein distance function can efficiently and reliably simulate bilingual orthographic similarity ratings. Orthographic similarity distributions of cognates an

  5. Lymphocyte GH-axis hormones in immunity.

    Science.gov (United States)

    Weigent, Douglas A

    2013-01-01

    The production and utilization of common ligands and their receptors by cells of the immune and neuroendocrine systems constitutes a biochemical information circuit between and within the immune and neuroendocrine systems. The sharing of ligands and receptors allows the immune system to serve as the sixth sense notifying the nervous system of the presence of foreign entities. Within this framework, it is also clear that immune cell functions can be altered by neuroendocrine hormones and that cells of the immune system have the ability to produce neuroendocrine hormones. This review summarizes a part of this knowledge with particular emphasis on growth hormone (GH). The past two decades have uncovered a lot of detail about the actions of GH, acting through its receptor, at the molecular and cellular level and its influence on the immune system. The production and action of immune cell-derived GH is less well developed although its important role in immunity is also slowly emerging. Here we discuss the production of GH, GH-releasing hormone (GHRH) and insulin-like growth factor-1 (IGF-1) and their cognate receptors on cells of the immune system and their influence via endocrine/autocrine/paracrine and intracrine pathways on immune function. The intracellular mechanisms of action of immune cell-derived GH are still largely unexplored, and it is anticipated that further work in this particular area will establish an important role for this source of GH in normal physiology and in pathologic situations.

  6. DMPD: Macrophage migration inhibitory factor and host innate immune responses tomicrobes. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 14620137 Macrophage migration inhibitory factor and host innate immune responses to...microbes. Calandra T. Scand J Infect Dis. 2003;35(9):573-6. (.png) (.svg) (.html) (.csml) Show Macrophage migration... inhibitory factor and host innate immune responses tomicrobes. PubmedID 14620137 Title Macrophage migration

  7. The impact of von Willebrand factor on factor VIII memory immune responses.

    Science.gov (United States)

    Chen, Juan; Schroeder, Jocelyn A; Luo, Xiaofeng; Shi, Qizhen

    2017-08-22

    Immune tolerance induction (ITI) with aggressive infusion of factor VIII (FVIII) is the current strategy used to eradicate FVIII inhibitors and restore normal FVIII pharmacokinetics in inhibitor patients. Whether the use of FVIII products containing von Willebrand factor (VWF) will affect the efficacy of ITI is still controversial. In this study, we explored the impact of VWF on FVIII memory immune responses in hemophilia A (HA) mice. A T-cell proliferation assay and cytokine profile analysis were used to study FVIII-primed CD4(+) T cells. When CD4(+) T cells from primed FVIII(null) mice were restimulated with recombinant human FVIII (rhF8) plus recombinant human VWF (rhVWF) in vitro, the percentages of daughter CD4(+) T cells were significantly decreased compared with the groups cultured with rhF8 only. Levels of interferon-γ and interleukin 10 were significantly lower in the rhF8 plus rhVWF groups than in the rhF8 groups. When memory B-cell pools from primed FVIII(null) mice were cultured with rhF8 with or without rhVWF to induce differentiation of memory B cells into antibody-secreting cells (ASCs), the number of ASCs was significantly lower in the rhF8 plus VWF group than in the rhF8 group. When memory B-cell pools were transferred into NSGF8KO mice followed by rhF8 immunization with or without rhVWF, the titers of anti-F8 inhibitors and total immunoglobulin G were significantly higher in the rhF8 group than in the rhF8 plus rhVWF group, with an average difference of 2.23- and 2.04-fold. Together, our data demonstrate that VWF attenuates FVIII memory immune responses in HA mice.

  8. Sociocultural factors and the success of immunization in selected ...

    African Journals Online (AJOL)

    Open Access DOWNLOAD FULL TEXT ... Both primary and secondary sources of data were utilized. In the case ... The study further suggests the need to sensitize the public more on the importance of immunization at all levels of government.

  9. Risk factors for discordant immune response among HIV-infected ...

    African Journals Online (AJOL)

    2012-11-02

    Nov 2, 2012 ... had a discordant immune response and 7% (n=67) a discordant virological response. On multivariate analysis ... initial rapid increase of memory CD4 cells, succeeded by a slow ... were obtained from the Human Research.

  10. Effect of immune nutritional support on immune function and inflammatory factor in postoperative patients with gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Hua-Jia Dai; Ke-Zhu Hou; Zu-Jin Cai; Qi Zhou; Song Zhu; Jian-Wei Bi

    2016-01-01

    Objective:To investigate the effect of immune nutritional support on immune function and inflammatory factor in postoperative patients with gastric cancer.Methods:A total of 100 patients with gastric cancer were selected and randomly divided into the observation group and the control group with 50 cases in each group. The control group received routine perioperative enteral and parenteral nutrition, on the basis of conventional nutritional support, and the observation group was given enteral nutrition emulsion immune support. Then, the immune function and the inflammatory factor of postoperative day 1 and day 7 were compared between the two groups.Results:(1) With the preoperative data as the basis, the levels of serum IgG, IgA, C3 and C4 decreased at the postoperative day 1 and then increased at the postoperative day 7, while the level of IgM showed an increasing trend and then a decreasing trend in the two groups, and the corresponding figures for the postoperative day 1 and day 7 were statistically different between the two groups. In the observation group, the levels of IgG, IgA, C3 and C4 were higher, while the level of IgM was lower at the postoperative day 1 and day 7 than that in the control group, and the differences were statistically significant; (2) With the preoperative data as the basis, the levels of serum TNF-α, IL-6 and CRP significantly increased at the postoperative day 1 and then decreased at the postoperative day 7 in the two groups, and the corresponding figures for the postoperative day 1 and day 7 in the observation group were lower than those in the control group, and the differences were statistically significant. Conclusion:Immune nutritional support can help to reduce the damage of immune function and the inflammatory response induced by surgery in patients with gastric cancer, which is worthy of clinical application.

  11. Tomato Cf resistance proteins mediate recognition of cognate homologous effectors from fungi pathogenic on diots and monocots

    NARCIS (Netherlands)

    Stergiopoulos, I.; Burg, van den H.A.; Ökmen, B.; Beenen, H.G.; Liere, van S.; Kema, G.H.J.; Wit, de P.J.G.M.

    2010-01-01

    Most fungal effectors characterized so far are species-specific and facilitate virulence on a particular host plant. During infection of its host tomato, Cladosporium fulvum secretes effectors that function as virulence factors in the absence of cognate Cf resistance proteins and induce

  12. Tomato Cf resistance proteins mediate recognition of cognate homologous effectors from fungi pathogenic on diots and monocots

    NARCIS (Netherlands)

    Stergiopoulos, I.; Burg, van den H.A.; Ökmen, B.; Beenen, H.G.; Liere, van S.; Kema, G.H.J.; Wit, de P.J.G.M.

    2010-01-01

    Most fungal effectors characterized so far are species-specific and facilitate virulence on a particular host plant. During infection of its host tomato, Cladosporium fulvum secretes effectors that function as virulence factors in the absence of cognate Cf resistance proteins and induce effector-tri

  13. Immunity

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920630 Effects of the spleen on immunestate of patients with gastric cancer.QIUDengbo (仇登波), et al. Dept General Surg,Union Hosp, Tongji Med Univ, Wuhan, 430022.Natl Med J China 1992; 72(6): 334-337. For analysing the effects of the spleen on im-mune state of gastric cancer patients.T-lym-

  14. GATA transcription factor required for immunity to bacterial and fungal pathogens.

    Directory of Open Access Journals (Sweden)

    Samantha Kerry

    Full Text Available In the past decade, Caenorhabditis elegans has been used to dissect several genetic pathways involved in immunity; however, little is known about transcription factors that regulate the expression of immune effectors. C. elegans does not appear to have a functional homolog of the key immune transcription factor NF-kappaB. Here we show that that the intestinal GATA transcription factor ELT-2 is required for both immunity to Salmonella enterica and expression of a C-type lectin gene, clec-67, which is expressed in the intestinal cells and is a good marker of S. enterica infection. We also found that ELT-2 is required for immunity to Pseudomonas aeruginosa, Enterococcus faecalis, and Cryptococcus neoformans. Lack of immune inhibition by DAF-2, which negatively regulates the FOXO transcription factor DAF-16, rescues the hypersusceptibility to pathogens phenotype of elt-2(RNAi animals. Our results indicate that ELT-2 is part of a multi-pathogen defense pathway that regulates innate immunity independently of the DAF-2/DAF-16 signaling pathway.

  15. Cognate Awareness--Raising in Late Childhood: Teachable and Useful

    Science.gov (United States)

    White, Joanna L.; Horst, Marlise

    2012-01-01

    This study is part of a larger investigation of the usefulness of instruction designed to raise cross-linguistic awareness in young Francophone learners of English in Quebec. In the research reported here, the focus is on cognates. Since previous research shows that learners typically fail to recognise many helpful similarities between words in a…

  16. Three languages, one ECHO: cognate effects in trilingual word recognition

    NARCIS (Netherlands)

    Lemhöfer, K.M.L.; Dijkstra, A.F.J.; Michel, M.C.

    2004-01-01

    Research on bilingual word recognition suggests that lexical access is non-selective with respect to language, i.e., that word representations of both languages become active during recognition. One piece of evidence is that bilinguals recognize cognates (words that are identical or similar in form

  17. VOCABULARY GUIDE OF COGNATE WORDS IN SPANISH AND ENGLISH.

    Science.gov (United States)

    KRIPPNER, STANLEY

    A VOCABULARY GUIDE OF COGNATE WORDS IN ENGLISH AND SPANISH IS PRESENTED. THE VALUE OF THE GUIDE RESTS ON THE ASSUMPTIONS THAT THE LEARNING OF SIMILAR WORDS IN BOTH LANGUAGES COULD CHANGE SPANISH-SPEAKING AMERICAN PUPILS' NEGATIVE ATTITUDE ABOUT ENGLISH AS WELL AS INCREASE THEIR VOCABULARY. WORDS IN THE "VELAZQUEZ SPANISH AND ENGLISH DICTIONARY" OF…

  18. Falsos amigos en lexicografica bilingue (False Cognates in Bilingual Lexicology).

    Science.gov (United States)

    Prado, Marcial

    1989-01-01

    Examines patterns of discrepancies in English and Spanish spelling, at the phonetic and morphological level, that result in orthographic false cognates. Twenty-two patterns are revealed at the phonetic level and 21 patterns are revealed at the morphological level (derivational affixes)--7 in prefixes and 12 in suffixes. (MLS)

  19. VOCABULARY GUIDE OF COGNATE WORDS IN SPANISH AND ENGLISH.

    Science.gov (United States)

    KRIPPNER, STANLEY

    A VOCABULARY GUIDE OF COGNATE WORDS IN ENGLISH AND SPANISH IS PRESENTED. THE VALUE OF THE GUIDE RESTS ON THE ASSUMPTIONS THAT THE LEARNING OF SIMILAR WORDS IN BOTH LANGUAGES COULD CHANGE SPANISH-SPEAKING AMERICAN PUPILS' NEGATIVE ATTITUDE ABOUT ENGLISH AS WELL AS INCREASE THEIR VOCABULARY. WORDS IN THE "VELAZQUEZ SPANISH AND ENGLISH DICTIONARY" OF…

  20. Factors affecting immunization coverage in urban slums of Odisha, India: implications on urban health policy

    Directory of Open Access Journals (Sweden)

    Santosh K. Prusty

    2013-10-01

    Full Text Available Infectious diseases are major causes of morbidity and mortality among children. One of the most cost-effective interventions for improved child survival is immunization, which has significant urban-rural divides. Slum dwellers constitute about one-third of Indian population, and most children still remain incompletely immunized. The main purpose of this study was to understand the factors behind partial or non-immunization of children aged 12-23 months in slum areas of Cuttack district, India. Session-based audit and a population-based survey were conducted in the urban slums of Cuttack city, April-June 2012. Total 79 children were assessed and their mothers were interviewed about the nature and quality of immunization services provided. Children fully immunized were 64.6%. Antigen-wise immunization coverage was highest for Bacillus Calmette-Guérin (BCG (96.2% and lowest for Measles (65.8%, which indicates high instances of late drop-out. Frequent illnesses of the child, lack of information about the scheduled date of immunization, frequent displacement of the family and lack of knowledge regarding the benefits of immunization were cited as the main factors behind coverage of immunization services. The study showed that there is an urgent need to revise the immunization strategy, especially for urban slums. District and sub-district officials should reduce instances of early and late dropouts and, in turn, improve complete immunization coverage. Community participation, intersectoral co-ordination and local decision making along with supportive supervision could be critical in addressing issues of drop-outs, supply logistics and community mobilization.

  1. Factors of Innate and Adaptive Local Immunity in Children with Primary Deficiencies of Antibody Formation

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    L.I. Chernyshova

    2013-11-01

    Full Text Available In 40 children with various types of primary immunodeficiencies (PID of antibody formation we examined factors of local immunity in saliva. It is found that in the saliva of children with PID of antibody formation in comparison with immunocompetent children the concentration of factors of adaptive immunity is significantly reduced. Lack of adaptive immunity in the PID of antibody formation to some extent is compensated by increased concentrations of innate immune factors on the mucous membranes — the free Sc, as well as lactoferrin in selective immunodeficiency of IgA. At PID of antibody formation we observed increased TNF-α level in the saliva, which may indicate the persistence of local inflammation on the membranes of the respiratory tract.

  2. Cognate interactions: extrafollicular IL-4 drives germinal-center reactions, a new role for an old cytokine.

    Science.gov (United States)

    Toellner, Kai-Michael

    2014-07-01

    Over the past 25 years it has become clear that B and T lymphocytes go through a range of interactions and migratory events when B cells differentiate to become high-affinity, antibody-secreting cells. This B-cell differentiation is associated with multiple sequential cognate interactions. In this issue of the European Journal of Immunology, Turqueti-Neves et al. [Eur. J. Immunol. 2014. 44: 2130-2138] show that IL-4, a cytokine well known as a regulator of Ig class switch recombination, has another as-yet-unappreciated role. The authors show that IL-4 produced by T-helper cells outside germinal centers has a major effect on the early stages of germinal-center B-cell differentiation. This Commentary will summarize their findings and relate them to what we know on the sequence of cognate interactions and migratory events B cells undergo during T-dependent immune responses.

  3. Identification of Immune-Relevant Factors Conferring Sarcoidosis Genetic Risk

    Science.gov (United States)

    Fischer, Annegret; Ellinghaus, David; Nutsua, Marcel; Hofmann, Sylvia; Montgomery, Courtney G.; Iannuzzi, Michael C.; Rybicki, Benjamin A.; Petrek, Martin; Mrazek, Frantisek; Pabst, Stefan; Grohé, Christian; Grunewald, Johan; Ronninger, Marcus; Eklund, Anders; Padyukov, Leonid; Mihailovic-Vucinic, Violeta; Jovanovic, Dragana; Sterclova, Martina; Homolka, Jiri; Nöthen, Markus M.; Herms, Stefan; Gieger, Christian; Strauch, Konstantin; Winkelmann, Juliane; Boehm, Bernhard O.; Brand, Stephan; Büning, Carsten; Schürmann, Manfred; Ellinghaus, Eva; Baurecht, Hansjörg; Lieb, Wolfgang; Nebel, Almut; Müller-Quernheim, Joachim; Franke, Andre

    2015-01-01

    Rationale: Genetic variation plays a significant role in the etiology of sarcoidosis. However, only a small fraction of its heritability has been explained so far. Objectives: To define further genetic risk loci for sarcoidosis, we used the Immunochip for a candidate gene association study of immune-associated loci. Methods: Altogether the study population comprised over 19,000 individuals. In a two-stage design, 1,726 German sarcoidosis cases and 5,482 control subjects were genotyped for 128,705 single-nucleotide polymorphisms using the Illumina Immunochip for the screening step. The remaining 3,955 cases, 7,514 control subjects, and 684 parents of affected offspring were used for validation and replication of 44 candidate and two established risk single-nucleotide polymorphisms. Measurements and Main Results: Four novel susceptibility loci were identified with genome-wide significance in the European case-control populations, located on chromosomes 12q24.12 (rs653178; ATXN2/SH2B3), 5q33.3 (rs4921492; IL12B), 4q24 (rs223498; MANBA/NFKB1), and 2q33.2 (rs6748088; FAM117B). We further defined three independent association signals in the HLA region with genome-wide significance, peaking in the BTNL2 promoter region (rs5007259), at HLA-B (rs4143332/HLA-B*0801) and at HLA-DPB1 (rs9277542), and found another novel independent signal near IL23R (rs12069782) on chromosome 1p31.3. Conclusions: Functional predictions and protein network analyses suggest a prominent role of the drug-targetable IL23/Th17 signaling pathway in the genetic etiology of sarcoidosis. Our findings reveal a substantial genetic overlap of sarcoidosis with diverse immune-mediated inflammatory disorders, which could be of relevance for the clinical application of modern therapeutics PMID:26051272

  4. The T-box Transcription Factor T-bet in Immunity and Autoimmunity

    Institute of Scientific and Technical Information of China (English)

    Stanford L. Peng

    2006-01-01

    The T-box transcription factor T-bet (Tbx21) has emerged as a key regulator of type 1-like immunity, playing critical roles in the establishment and/or maintenance of effector cell fates in T and B lymphocytes, as well as dendritic cells and natural killer cells. Several autoimmune diseases, especially those classically considered related to T helper 1 (Th1) immunity, appear to require T-bet, at least as judged in mouse models. This review summarizes a current understanding of T-bet's role in immunity, as well as its importance in autoimmunity, with implications for therapeutic intervention.

  5. Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity

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    Gisela Canedo-Marroquín

    2017-08-01

    Full Text Available The Human Respiratory Syncytial Virus (hRSV is a major cause of acute lower respiratory tract infections (ARTIs and high rates of hospitalizations in children and in the elderly worldwide. Symptoms of hRSV infection include bronchiolitis and pneumonia. The lung pathology observed during hRSV infection is due in part to an exacerbated host immune response, characterized by immune cell infiltration to the lungs. HRSV is an enveloped virus, a member of the Pneumoviridae family, with a non-segmented genome and negative polarity-single RNA that contains 10 genes encoding for 11 proteins. These include the Fusion protein (F, the Glycoprotein (G, and the Small Hydrophobic (SH protein, which are located on the virus surface. In addition, the Nucleoprotein (N, Phosphoprotein (P large polymerase protein (L part of the RNA-dependent RNA polymerase complex, the M2-1 protein as a transcription elongation factor, the M2-2 protein as a regulator of viral transcription and (M protein all of which locate inside the virion. Apart from the structural proteins, the hRSV genome encodes for the non-structural 1 and 2 proteins (NS1 and NS2. HRSV has developed different strategies to evade the host immunity by means of the function of some of these proteins that work as virulence factors to improve the infection in the lung tissue. Also, hRSV NS-1 and NS-2 proteins have been shown to inhibit the activation of the type I interferon response. Furthermore, the hRSV nucleoprotein has been shown to inhibit the immunological synapsis between the dendritic cells and T cells during infection, resulting in an inefficient T cell activation. Here, we discuss the hRSV virulence factors and the host immunological features raised during infection with this virus.

  6. Snarks, Quarks and Cognates: An Elusive Fundamental Particle in Reading Comprehension.

    Science.gov (United States)

    Holmes, John L.

    1986-01-01

    Discusses recognition of cognates used in teaching materials prepared by the English for Specific Purposes Project for academic courses. Presents suggestions based on theoretical considerations of cognate recognition. Examines, by way of protocol studies, how foreign students of English make use of cognate recognition. Suggests that strategies for…

  7. Identifying Spanish-English Cognates to Scaffold Instruction for Latino ELs

    Science.gov (United States)

    Montelongo, Jose A.; Hernandez, Anita; Herter, Roberta Joan

    2011-01-01

    Spanish-English cognates have been used for decades to facilitate the acquisition of English by Latino English learners (ELs). Using the online program, WordSift, in tandem with the online Find-a-Cognate database, teachers can identify important Spanish-English cognates and noncognate words in text. With this information, teachers can plan and…

  8. Cognate Awareness in French Immersion Students: Contributions to Grade 2 Reading Comprehension

    Science.gov (United States)

    Hipfner-Boucher, Kathleen; Pasquarella, Adrian; Chen, Xi; Deacon, S. Hélène

    2016-01-01

    Cognate awareness is the ability to recognize the cognate relationship between words in two etymologically related languages. The current study examined the development of cognate awareness and its contribution to French (second language) reading comprehension among Canadian French immersion children. Eighty-one students were tested at the end of…

  9. Discovery of immune related factors in Fenneropenaeus chinensis by annotation of ESTs

    Institute of Scientific and Technical Information of China (English)

    SHEN Yaoqing; XIANG Jianhai; WANG Bing; LI Fuhua; TONG Wei

    2004-01-01

    A total of 10446 expressed sequence tags (ESTs) are obtained by a large-scale sequencing of a cDNA library from cephalothorax of adult Fenneropenaeus chinensis.An EST analysis platform was built up based on local computers and bioinformatic techniques were used to annotate these ESTs in order to promptly find possible functional genes, especially for immune related factors.About 4% of the ESTs show similarity to the coding sequences of such factors, including lectin, serine protease, serpin, lysozyme, etc.These ESTs provide a partial profile of the immune system in F.chinensis and useful information for further study on these genes.

  10. [Factors associated with influenza immunization in primary care health workers].

    Science.gov (United States)

    Montserrat-Capdevila, Josep; Godoy, Pere; Marsal, Josep Ramon; Barbé-Illa, Ferran

    2015-01-01

    To identify the influenza vaccination coverage in healthcare workers in primary care and to determine the factors associated with vaccination (2013-2014 season). A cross-sectional study was carried out among 287 healthcare workers who completed a questionnaire that included questions about knowledge, beliefs and attitudes to influenza and vaccination. We estimated the vaccine coverage and identified the variables associated with vaccination of healthcare workers by using non-conditional logistic regression models. The participation rate was 47.2%. Vaccination coverage was 60.3% and was higher in workers older than 55 years, women and pediatricians. The factors associated with healthcare worker vaccination were the perception that vaccination confers protection (aOR: 11.1; 95%CI: 3.41-35.9) and the perception that it is effective (aOR: 7.5; 95%CI: 0.9-59.3). No association was found between receiving the vaccine and knowledge of influenza or vaccination. However, an association was found with prescribing vaccination to pregnant women, to persons older than 65 years, and to immunosuppressed individuals. Strategies should be designed to increase coverage, based on changing negative attitudes of healthcare workers to vaccination. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  11. The cognate advantage in bilingual aphasia: Now you see it, now you don't.

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    Emma Hughes

    2015-05-01

    Full Text Available Background: The role of cognateness in bilingual language production has been the focus of much investigation. Many studies have found a cognate facilitation effect for reaction times and accuracy in naming in control participants (Costa, Caramazza & Sebastien-Galles, 2000; Rosselli, Ardila, Jurado,& Salvatierra, 2012 but the findings are by no means unequivocal e.g. Siyambalapitiya et al, 2009 observed a reversal of the cognate facilitation effect in older participants. The effect of cognateness has also been investigated in aphasic participants; Roberts & Deslauriers (199 observed a strong picture naming advantage for cognate words over non-cognate words, though no individual data were reported. Several case studies have reported cognate advantage in individuals, though results vary dependent on task and on the individual (Detry, Pillon & De Partz, 2005; Lalor & Kirsner, 2001. Furthermore, an inhibitory effect for cognate words has also been observed (Tiwari & Krishnan 2015. Overall, the above findings serve to illustrate that the facilitatory effect of cognate words is uncertain, and further investigation is required. Research Question: Does task type affect the cognate advantage in Welsh-English bilingual speakers? It is expected that patients will present with a picture naming advantage for cognate items. The expectations for a cognate advantage in translation are less assured, as the presentation of a cognate word in one language may inhibit access to its translation equivalent due to the phonological overlap, or the similarity may be facilitatory in activating the phonological representation of the target. Participants: 7 Welsh-English early proficient bilingual aphasic participants were selected for participation. Each patient scored significantly lower (p<.05 than age-matched controls (N=37 on at least one task using the modified t-tests for single cases (Crawford & Howell, 1998 Methods: Picture naming and translation tasks were

  12. Immunity to nerve growth factor and the effect on motor unit reinnervation in the rabbit.

    Science.gov (United States)

    Finkelstein, D I; Luff, A R; Schuijers, J A

    1992-05-01

    The trophic effects of nerve growth factor (NGF) on sympathetic, peripheral afferent, and other neural crest-derived cells have been intensively investigated. More recently, NGF has been shown to have an influence on motoneurons. This study was undertaken to investigate whether NGF had any influence on the mechanical or histological properties of reinnervated motor units. Three groups of rabbits were used: normal rabbits, rabbits in which the nerve to medial gastrocnemius (MG) was cut and allowed to reinnervate for 56 days, and rabbits in which the MG nerve reinnervated in the presence of immunity to NGF. Immunity to NGF did not affect the ability of motor axons to reinnervate a muscle, nor were the contractile characteristics of the motor units altered. The size of horseradish peroxidase-labeled motoneurons was not influenced by immunization against NGF; however, the distribution of afferent neuron sizes was altered. Conduction velocity of motor axons proximal to the neuroma was significantly faster after immunization against NGF. Transection and subsequent reinnervation by a peripheral nerve normally causes an increase in myelin thickness proximal to the neuroma. However, immunization against NGF appeared to decrease the magnitude of myelin thickening. It was concluded that immunization against NGF affects motor axonal conduction velocity via an influence on the neural crest-derived Schwann cells.

  13. Tumor necrosis factor-α-induced protein 1 and immunity to hepatitis B virus

    Institute of Scientific and Technical Information of China (English)

    Marie C Lin; Nikki P Lee; Ning Zheng; Pai-Hao Yang; Oscar G Wong; Hsiang-Fu Kung; Chee-Kin Hui; John M Luk; George Ka-Kit Lau

    2005-01-01

    AIM: To compare the gene expression profile in a pair of HBV-infected twins.METHODS: The gene expression profile was compared in a pair of HBV-infected twins.RESULTS: The twins displayed different disease outcomes. One acquired natural immunity against HBV,whereas the other became a chronic HBV carrier. Eightyeight and forty-six genes were found to be up- or downregulated in their PBMCs, respectively. Tumor necrosis factor-alpha-induced protein 1 (TNF-αIP1) that expressed at a higher level in the HBV-immune twins was identified and four pairs of siblings with HBV immunity by RTPCR. However, upon HBV core antigen stimulation,TNF-αIP1 was downregulated in PBMCs from subjects with immunity, whereas it was slightly upregulated in HBV carriers. Bioinformatics analysis revealed a K+channel tetramerization domain in TNF-αIP1 that shares a significant homology with some human, mouse, and C elegan proteins.CONCLUSION: TNF-αIP1 may play a role in the innate immunity against HBV.

  14. Immunization with Dendritic Cells Pulsed ex vivo with Recombinant Chlamydial Protease-Like Activity Factor Induces Protective Immunity Against Genital Chlamydia muridarum Challenge

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    Bernard eArulanandam

    2011-12-01

    Full Text Available We have shown that immunization with soluble recombinant (r chlamydial protease-like activity factor (rCPAF and a T helper (Th 1 type adjuvant can induce significantly enhanced bacterial clearance and protection against Chlamydia–induced pathological sequelae in the genital tract. In this study, we investigated the use of bone marrow derived dendritic cells (BMDCs pulsed ex vivo with rCPAF+CpG in an adoptive subcutaneous immunization for the ability to induce protective immunity against genital chlamydial infection. We found that BMDCs pulsed with rCPAF+CpG efficiently up-regulated the expression of activation markers CD86, CD80, CD40 and major histocompatibility complex class II (MHC II, and secreted interleukin-12, but not IL-10 and IL-4. Mice adoptively immunized with rCPAF+CpG-pulsed BMDCs or UV-EB+CpG-pulsed BMDCs produced elevated levels of antigen-specific IFN- and enhanced IgG1 and IgG2a antibodies. Moreover, mice immunized with rCPAF+CpG-pulsed BMDCs or UV-EB+CpG-pulsed BMDCs exhibited significantly reduced genital Chlamydia shedding, accelerated resolution of infection, and reduced oviduct pathology when compared to infected mock-immunized animals. These results suggest that adoptive subcutaneous immunization with ex vivo rCPAF-pulsed BMDCs is an effective approach, comparable to that induced by UV-EB-BMDCs, for inducing robust anti-Chlamydia immunity.

  15. Teaching cognates in isolation and context: a practical note on Montelongo, et al. (2009).

    Science.gov (United States)

    Rodriguez, Timothy A

    2010-10-01

    The use of cognates in teaching word identification and vocabulary meaning is an underused resource in the teaching of English-language learners, especially for learners whose language is similar to English, e.g., Spanish. A recent study by Montelongo, Hernandez, Herter, and Hernandez reported that the effect of initial consonants was strong for recognizing words in isolation. In addition, they pointed out that cognates containing suffixes identical between English and Spanish were more quickly recognized than cognates containing similar but not identical suffixes. Further, they stated teachers would do well to take these differences into account when employing a cognate strategy with their Latino English-language learners. The purpose of this response is to discuss how different types of cognates and their various meanings may be examined by educators and students when employing cognates as a strategy in learning English.

  16. Effects of cognate status on word comprehension in second language learners: an ERP investigation.

    Science.gov (United States)

    Midgley, Katherine J; Holcomb, Phillip J; Grainger, Jonathan

    2011-07-01

    ERPs were used to explore the different patterns of processing of cognate and noncognate words in the first (L1) and second (L2) language of a population of second language learners. L1 English students of French were presented with blocked lists of L1 and L2 words, and ERPs to cognates and noncognates were compared within each language block. For both languages, cognates had smaller amplitudes in the N400 component when compared with noncognates. L1 items that were cognates showed early differences in amplitude in the N400 epoch when compared with noncognates. L2 items showed later differences between cognates and noncognates than L1 items. The results are discussed in terms of how cognate status affects word recognition in second language learners.

  17. Cross-language distributions of high frequency and phonetically similar cognates.

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    Job Schepens

    Full Text Available The coinciding form and meaning similarity of cognates, e.g. 'flamme' (French, 'Flamme' (German, 'vlam' (Dutch, meaning 'flame' in English, facilitates learning of additional languages. The cross-language frequency and similarity distributions of cognates vary according to evolutionary change and language contact. We compare frequency and orthographic (O, phonetic (P, and semantic similarity of cognates, automatically identified in semi-complete lexicons of six widely spoken languages. Comparisons of P and O similarity reveal inconsistent mappings in language pairs with deep orthographies. The frequency distributions show that cognate frequency is reduced in less closely related language pairs as compared to more closely related languages (e.g., French-English vs. German-English. These frequency and similarity patterns may support a better understanding of cognate processing in natural and experimental settings. The automatically identified cognates are available in the supplementary materials, including the frequency and similarity measurements.

  18. Is there a cognate advantage for typically developing Spanish-speaking English-language learners?

    Science.gov (United States)

    Kelley, Alaina; Kohnert, Kathryn

    2012-04-01

    Cross-linguistic cognates are words that share form and meaning in two languages (e.g., helicopter-helicóptero); translation equivalents are words that share meaning but not form (e.g., house-casa). Research consistently demonstrates a performance speed and/or accuracy advantage for processing cognates versus noncognates in bilingual adults; studies with children are limited, with equivocal results. We investigated the potential for a cognate advantage for processing expressive and receptive vocabulary in the spoken (vs. written) modality in typically developing Spanish-speaking English-language learners (ELLs). Thirty 8- to 13-year-old native Spanish-speaking children learning English as their second language completed standardized vocabulary tests in spoken English. Each test item was classified as a cognate or noncognate based on phonological overlap with its Spanish translation. Group and individual analyses were used to examine the effects of cognates. At the group level, children's test scores were higher for items that were classified as cognates as compared to noncognates of comparable difficulty. However, not all children demonstrated this cognate advantage. Age predicted significant amounts of variance in cognate performance on the receptive test. Overall, typically developing Spanish-speaking school-age ELL students demonstrated a cognate advantage. There was also considerable within-group variation in performance. Clinical implications are discussed, and directions for future study are provided.

  19. Patterns in the acquisition of some cognate consonants in portuguese Patterns in the acquisition of some cognate consonants in portuguese

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    Marígia Viana

    2008-04-01

    Full Text Available Acquiring the phonology of a language requires the development of a high complex series of processes on which, unfortunately, we still lack much information. As a result of the uniqueness of languages we are faced with the problem of identifying these processes and their ordering of appearance in apparently a quite distinct manner within each language and from child to child. While the general trend is that children use systematic patterns to distinguish between cognate pairs of sounds, these patterns may vary from language to language. Moreover, this discrimination task may be a result of the acquisition of different skills acquired at different stages (cf. Macken and Barton, 1979. Acquiring the phonology of a language requires the development of a high complex series of processes on which, unfortunately, we still lack much information. As a result of the uniqueness of languages we are faced with the problem of identifying these processes and their ordering of appearance in apparently a quite distinct manner within each language and from child to child. While the general trend is that children use systematic patterns to distinguish between cognate pairs of sounds, these patterns may vary from language to language. Moreover, this discrimination task may be a result of the acquisition of different skills acquired at different stages (cf. Macken and Barton, 1979.

  20. Hepatitis B virus infection risk factors and immunity among sexually transmitted disease clinic clients.

    Science.gov (United States)

    Trepka, Mary Jo; Weisbord, Joanna S; Zhang, Guoyan; Brewer, Toye

    2003-12-01

    Hepatitis B virus (HBV) infection is a sexually transmitted infection that can be prevented with hepatitis B vaccination. The goal was to determine prevalence and risk factors for HBV infection and immunity among sexually transmitted disease (STD) clinic clients. In this cross-sectional study, consenting adult STD clinic clients were interviewed regarding HBV risk factors and vaccination history, and blood was drawn for HBV serologic testing. Of the 682 participants, 154 (22.6%) had antibody to hepatitis B core antigen, indicating previous infection, and 64 (9.4%) had only antibody to hepatitis B surface antigen, indicating immunity as a result of hepatitis B vaccination. Only 130 (19.1%) of all participants reported receiving at least one dose of hepatitis B vaccine. The majority of clients were susceptible to HBV, were at high risk for HBV infection, and would benefit from hepatitis B vaccination.

  1. Legionella metaeffector exploits host proteasome to temporally regulate cognate effector.

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    Tomoko Kubori

    Full Text Available Pathogen-associated secretion systems translocate numerous effector proteins into eukaryotic host cells to coordinate cellular processes important for infection. Spatiotemporal regulation is therefore important for modulating distinct activities of effectors at different stages of infection. Here we provide the first evidence of "metaeffector," a designation for an effector protein that regulates the function of another effector within the host cell. Legionella LubX protein functions as an E3 ubiquitin ligase that hijacks the host proteasome to specifically target the bacterial effector protein SidH for degradation. Delayed delivery of LubX to the host cytoplasm leads to the shutdown of SidH within the host cells at later stages of infection. This demonstrates a sophisticated level of coevolution between eukaryotic cells and L. pneumophila involving an effector that functions as a key regulator to temporally coordinate the function of a cognate effector protein.

  2. Anthrax lethal factor as an immune target in humans and transgenic mice and the impact of HLA polymorphism on CD4+ T cell immunity.

    Science.gov (United States)

    Ascough, Stephanie; Ingram, Rebecca J; Chu, Karen K; Reynolds, Catherine J; Musson, Julie A; Doganay, Mehmet; Metan, Gökhan; Ozkul, Yusuf; Baillie, Les; Sriskandan, Shiranee; Moore, Stephen J; Gallagher, Theresa B; Dyson, Hugh; Williamson, E Diane; Robinson, John H; Maillere, Bernard; Boyton, Rosemary J; Altmann, Daniel M

    2014-05-01

    Bacillus anthracis produces a binary toxin composed of protective antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). Most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity, in contrast to which understanding of cellular immunity to these toxins and its impact on infection is limited. We characterized CD4+ T cell immunity to LF in a panel of humanized HLA-DR and DQ transgenic mice and in naturally exposed patients. As the variation in antigen presentation governed by HLA polymorphism has a major impact on protective immunity to specific epitopes, we examined relative binding affinities of LF peptides to purified HLA class II molecules, identifying those regions likely to be of broad applicability to human immune studies through their ability to bind multiple alleles. Transgenics differing only in their expression of human HLA class II alleles showed a marked hierarchy of immunity to LF. Immunogenicity in HLA transgenics was primarily restricted to epitopes from domains II and IV of LF and promiscuous, dominant epitopes, common to all HLA types, were identified in domain II. The relevance of this model was further demonstrated by the fact that a number of the immunodominant epitopes identified in mice were recognized by T cells from humans previously infected with cutaneous anthrax and from vaccinated individuals. The ability of the identified epitopes to confer protective immunity was demonstrated by lethal anthrax challenge of HLA transgenic mice immunized with a peptide subunit vaccine comprising the immunodominant epitopes that we identified.

  3. Anthrax lethal factor as an immune target in humans and transgenic mice and the impact of HLA polymorphism on CD4+ T cell immunity.

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    Stephanie Ascough

    2014-05-01

    Full Text Available Bacillus anthracis produces a binary toxin composed of protective antigen (PA and one of two subunits, lethal factor (LF or edema factor (EF. Most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity, in contrast to which understanding of cellular immunity to these toxins and its impact on infection is limited. We characterized CD4+ T cell immunity to LF in a panel of humanized HLA-DR and DQ transgenic mice and in naturally exposed patients. As the variation in antigen presentation governed by HLA polymorphism has a major impact on protective immunity to specific epitopes, we examined relative binding affinities of LF peptides to purified HLA class II molecules, identifying those regions likely to be of broad applicability to human immune studies through their ability to bind multiple alleles. Transgenics differing only in their expression of human HLA class II alleles showed a marked hierarchy of immunity to LF. Immunogenicity in HLA transgenics was primarily restricted to epitopes from domains II and IV of LF and promiscuous, dominant epitopes, common to all HLA types, were identified in domain II. The relevance of this model was further demonstrated by the fact that a number of the immunodominant epitopes identified in mice were recognized by T cells from humans previously infected with cutaneous anthrax and from vaccinated individuals. The ability of the identified epitopes to confer protective immunity was demonstrated by lethal anthrax challenge of HLA transgenic mice immunized with a peptide subunit vaccine comprising the immunodominant epitopes that we identified.

  4. Anthrax Lethal Factor as an Immune Target in Humans and Transgenic Mice and the Impact of HLA Polymorphism on CD4+ T Cell Immunity

    Science.gov (United States)

    Ascough, Stephanie; Ingram, Rebecca J.; Chu, Karen K.; Reynolds, Catherine J.; Musson, Julie A.; Doganay, Mehmet; Metan, Gökhan; Ozkul, Yusuf; Baillie, Les; Sriskandan, Shiranee; Moore, Stephen J.; Gallagher, Theresa B.; Dyson, Hugh; Williamson, E. Diane; Robinson, John H.; Maillere, Bernard; Boyton, Rosemary J.; Altmann, Daniel M.

    2014-01-01

    Bacillus anthracis produces a binary toxin composed of protective antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). Most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity, in contrast to which understanding of cellular immunity to these toxins and its impact on infection is limited. We characterized CD4+ T cell immunity to LF in a panel of humanized HLA-DR and DQ transgenic mice and in naturally exposed patients. As the variation in antigen presentation governed by HLA polymorphism has a major impact on protective immunity to specific epitopes, we examined relative binding affinities of LF peptides to purified HLA class II molecules, identifying those regions likely to be of broad applicability to human immune studies through their ability to bind multiple alleles. Transgenics differing only in their expression of human HLA class II alleles showed a marked hierarchy of immunity to LF. Immunogenicity in HLA transgenics was primarily restricted to epitopes from domains II and IV of LF and promiscuous, dominant epitopes, common to all HLA types, were identified in domain II. The relevance of this model was further demonstrated by the fact that a number of the immunodominant epitopes identified in mice were recognized by T cells from humans previously infected with cutaneous anthrax and from vaccinated individuals. The ability of the identified epitopes to confer protective immunity was demonstrated by lethal anthrax challenge of HLA transgenic mice immunized with a peptide subunit vaccine comprising the immunodominant epitopes that we identified. PMID:24788397

  5. Sex and death: the effects of innate immune factors on the sexual reproduction of malaria parasites.

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    Ricardo S Ramiro

    2011-03-01

    Full Text Available Malaria parasites must undergo a round of sexual reproduction in the blood meal of a mosquito vector to be transmitted between hosts. Developing a transmission-blocking intervention to prevent parasites from mating is a major goal of biomedicine, but its effectiveness could be compromised if parasites can compensate by simply adjusting their sex allocation strategies. Recently, the application of evolutionary theory for sex allocation has been supported by experiments demonstrating that malaria parasites adjust their sex ratios in response to infection genetic diversity, precisely as predicted. Theory also predicts that parasites should adjust sex allocation in response to host immunity. Whilst data are supportive, the assumptions underlying this prediction - that host immune responses have differential effects on the mating ability of males and females - have not yet been tested. Here, we combine experimental work with theoretical models in order to investigate whether the development and fertility of male and female parasites is affected by innate immune factors and develop new theory to predict how parasites' sex allocation strategies should evolve in response to the observed effects. Specifically, we demonstrate that reactive nitrogen species impair gametogenesis of males only, but reduce the fertility of both male and female gametes. In contrast, tumour necrosis factor-α does not influence gametogenesis in either sex but impairs zygote development. Therefore, our experiments demonstrate that immune factors have complex effects on each sex, ranging from reducing the ability of gametocytes to develop into gametes, to affecting the viability of offspring. We incorporate these results into theory to predict how the evolutionary trajectories of parasite sex ratio strategies are shaped by sex differences in gamete production, fertility and offspring development. We show that medical interventions targeting offspring development are more likely

  6. Salidroside exhibits anti-dengue virus activity by upregulating host innate immune factors.

    Science.gov (United States)

    Sharma, Navita; Mishra, K P; Ganju, Lilly

    2016-12-01

    Dengue is an arboviral disease with no effective therapy available. Therefore, there is an urgent need to find a potent antiviral agent against dengue virus (DENV). In the present study, salidroside, a main bioactive compound of Rhodiola rosea, was evaluated for its antiviral potential against DENV serotype-2 infection and its effect on host innate immune factors. Antiviral effects of salidroside were examined in DENV-infected cells by western blotting, flow cytometry and real-time PCR. Its underlying mechanism involved in antiviral action was determined by evaluating expression of host innate immune factors including RIG-I, IRF-3, IRF-7, PKR, P-eIF2α and NF-κB. Salidroside potently inhibited DENV infection by decreasing DENV envelope protein expression more than tenfold. Salidroside exerts its antiviral activity by increasing expression of RNA helicases such as RIG-I, thereby initiating a downstream signaling cascade that induces upregulation of IRF-3 and IRF-7. It prevents viral protein synthesis by increasing the expression of PKR and P-eIF2α while decreasing NF-κB expression. It was also found to induce the expression of IFN-α. In addition, the number of NK cells and CD8(+) T cells were also found to be increased by salidroside treatment in human PBMCs, which are important in limiting DENV replication during early stages of infection. The findings presented here suggest that salidroside exhibits antiviral activity against DENV by inhibiting viral protein synthesis and boosting host immunity by increasing the expression of host innate immune factors and hence could be considered for the development of an effective therapeutic agent against DENV infection.

  7. The Sbi protein is a multifunctional immune evasion factor of Staphylococcus aureus.

    Science.gov (United States)

    Smith, Emma Jane; Visai, Livia; Kerrigan, Steven W; Speziale, Pietro; Foster, Timothy J

    2011-09-01

    The second immunoglobulin-binding protein (Sbi) of Staphylococcus aureus has two N-terminal domains that bind the Fc region of IgG in a fashion similar to that of protein A and two domains that can bind to the complement protein C3 and promote its futile consumption in the fluid phase. It has been proposed that Sbi helps bacteria to avoid innate immune defenses. By comparing a mutant defective in Sbi with mutants defective in protein A, clumping factor A, iron-regulated surface determinant H, and capsular polysaccharide, it was shown that Sbi is indeed an immune evasion factor that promotes bacterial survival in whole human blood and the avoidance of neutrophil-mediated opsonophagocytosis. Sbi is present in the culture supernatant and is also associated with the cell envelope. S. aureus strains that expressed truncates of Sbi lacking N-terminal domains D1 and D2 (D1D2) or D3 and D4 (D3D4) or a C-terminal truncate that was no longer retained in the cell envelope were analyzed. Both the secreted and envelope-associated forms of Sbi contributed to immune evasion. The IgG-binding domains contributed only when Sbi was attached to the cell, while only the secreted C3-binding domains were biologically active.

  8. The Role of Genetic and Immune Factors for the Pathogenesis of Primary Sclerosing Cholangitis in Childhood

    Science.gov (United States)

    Campos Silva, Soraya Luiza; Marques de Miranda, Débora; Ferreira, Alexandre Rodrigues

    2016-01-01

    Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by chronic inflammation of the biliary tree resulting in liver fibrosis. PSC is more common in male less than 40 years of age. The diagnosis of PSC is based on clinical, laboratory, image, and histological findings. A biochemical profile of mild to severe chronic cholestasis can be observed. Endoscopic retrograde cholangiography is the golden standard method for diagnosis, but magnetic resonance cholangiography is currently also considered a first-line method of investigation. Differences in clinical and laboratory findings were observed in young patients, including higher incidence of overlap syndromes, mostly with autoimmune hepatitis, higher serum levels of aminotransferases and gamma-glutamyl transferase, and lower incidence of serious complications as cholangiocarcinoma. In spite of the detection of several HLA variants as associated factors in large multicenter cohorts of adult patients, the exact role and pathways of these susceptibility genes remain to be determined in pediatric population. In addition, the literature supports a role for an altered immune response to pathogens in the pathogenesis of PSC. This phenomenon contributes to abnormal immune system activation and perpetuation of the inflammatory process. In this article, we review the role of immune and genetic factors in the pathogenesis of PSC in pediatric patients. PMID:27882046

  9. Interaction between viral RNA silencing suppressors and host factors in plant immunity.

    Science.gov (United States)

    Nakahara, Kenji S; Masuta, Chikara

    2014-08-01

    To elucidate events in the molecular arms race between the host and pathogen in evaluating plant immunity, a zigzag model is useful for uncovering aspects common to different host-pathogen interactions. By analogy of the steps in virus-host interactions with the steps in the standard zigzag model outlined in recent papers, we may regard RNA silencing as pattern-triggered immunity (PTI) against viruses, RNA silencing suppressors (RSSs) as effectors to overcome host RNA silencing and resistance gene (R-gene)-mediated defense as effector-triggered immunity (ETI) recognizing RSSs as avirulence proteins. However, because the standard zigzag model does not fully apply to some unique aspects in the interactions between a plant host and virus, we here defined a model especially designed for viruses. Although we simplified the phenomena involved in the virus-host interactions in the model, certain specific interactive steps can be explained by integrating additional host factors into the model. These host factors are thought to play an important role in maintaining the efficacy of the various steps in the main pathway of defense against viruses in this model for virus-plant interactions. For example, we propose candidates that may interact with viral RSSs to induce the resistance response. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. HIV-derived lentiviral particles promote T-cell independent activation and differentiation of naïve cognate conventional B2-cells in vitro.

    Science.gov (United States)

    Gardt, Oliver; Grewe, Bastian; Tippler, Bettina G; Überla, Klaus; Temchura, Vladimir V

    2013-10-17

    In animal models, lentiviral particles (LP) were shown to be promising HIV vaccine candidates. Since little is known about the direct impact of LP on antigen-specific B cells, we incorporated Hen Egg Lysozyme (HEL) into LP (HEL-LP) derived from HIV to study their effect on HEL-specific, B cell receptor-transgenic B-cells (HEL(+)B-cells) in vitro. We observed preferential binding of HEL-LP to HEL(+)B-cells and their efficient internalization. HEL-LP were able to effectively cross-link B-cell receptors as indicated by the loss of surface CD62L. In the absence of CD4(+) T-cells, other activation events induced by LP in cognate naïve B-cells included increased expression of activation and co-stimulatory molecules as well as an enhanced proliferative response. Additionally, the B-cell phenotype shifted toward a germinal center pattern with further differentiation into memory and IgG3- and IgA-producing cells. The observed CD4(+) T-cell independent activation and differentiation may be due to LP-induced expression of CD40L by a subset of cognate B-cells. Thus, even in the absence of CD4(+) T-cells LP provide strong direct activation signals to cognate naïve B-cells, which may contribute to the strong humoral immune responses observed after LP immunization. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Teaching English-Spanish Cognates Using the Texas 2x2 Picture Book Reading Lists

    Science.gov (United States)

    Montelongo, José A.; Hernández, Anita C.; Herter, Roberta J.

    2015-01-01

    English-Spanish cognates are words that possess identical or nearly identical spellings and meanings in both English and Spanish as a result of being derived mainly from Latin and Greek. Of major importance is the fact that many of the more than 20,000 cognates in English are academic vocabulary words, terms essential for comprehending school…

  12. Is There a Cognate Advantage for Typically Developing Spanish-Speaking English-Language Learners?

    Science.gov (United States)

    Kelley, Alaina; Kohnert, Kathryn

    2012-01-01

    Purpose: Cross-linguistic cognates are words that share form and meaning in two languages (e.g., "helicopter-helicoptero"); translation equivalents are words that share meaning but not form (e.g., "house-casa"). Research consistently demonstrates a performance speed and/or accuracy advantage for processing cognates versus noncognates in bilingual…

  13. Reduction of Factor VIII Inhibitor Titers During Immune Tolerance Induction With Recombinant Factor VIII-Fc Fusion Protein.

    Science.gov (United States)

    Groomes, Charles L; Gianferante, David M; Crouch, Gary D; Parekh, Dina S; Scott, David W; Lieuw, Kenneth

    2016-05-01

    The development of inhibitors toward factor VIII (FVIII) is a common and serious complication of hemophilia A (HA) therapy. Patients with hemophilia who develop inhibitors often undergo time- and resource-intensive immune tolerance induction (ITI) protocols. We report a 15-month-old male with severe HA and a high-titer inhibitor that occurred while receiving prophylactic treatment with recombinant FVIII (rFVIII), in whom significant inhibitor titer reduction was achieved with thrice weekly infusions of a new, prolonged half-life rFVIII-Fc fusion protein product (trade name Eloctate). Further studies are warranted to explore the potential of Eloctate in ITI protocols.

  14. Written cognate treatment in a Welsh-English bilingual aphasic patient

    Directory of Open Access Journals (Sweden)

    Polly Barr

    2015-05-01

    Weighted Statistics (Howard, Best, & Nickels, 2015 will be used to investigate improvement from baselines to post-tests. This will establish whether there are effects of English treatment on the treated sets (a, b and c and the untreated English and Welsh sets (d,e,f,g. If treatment improves written production of the treated sets, then we can attribute this to strengthening lexical representation and investigate generalisation to untreated sets. We will specifically be looking at whether cognates when treated in English improve in Welsh compared to non-cognates, but also if any inhibition occurs if cognates share exactly the same phonology (sets a and e compared to if cognates have slightly differing phonology (sets c and f. The results of the study will be used to inform bilingual language models on interconnectivity and the special status of cognates as well as inform us of cost and time effective aphasia therapy.

  15. Inflammatory transcription factors as activation markers and functional readouts in immune-to-brain communication.

    Science.gov (United States)

    Rummel, Christoph

    2016-05-01

    Immune-to-brain communication pathways involve humoral mediators, including cytokines, central modulation by neuronal afferents and immune cell trafficking to the brain. During systemic inflammation these pathways contribute to mediating brain-controlled sickness symptoms including fever. Experimentally, activation of these signaling pathways can be mimicked and studied when injecting animals with pathogen associated molecular patterns (PAMPS). One central component of the brain inflammatory response, which leads, for example, to fever induction, is transcriptional activation of brain cells via cytokines and PAMPS. We and others have studied the spatiotemporal activation and the physiological significance of transcription factors for the induction of inflammation within the brain and the manifestation of fever. Evidence has revealed a role of nuclear factor (NF)κB in the initiation, signal transducer and activator of transcription (STAT)3 in the maintenance and NF-interleukin (IL)6 in the maintenance or even termination of brain-inflammation and fever. Moreover, psychological stressors, such as exposure to a novel environment, leads to increased body core temperature and genomic NF-IL6-activation, suggesting a potential use of NF-IL6-immunohistochemistry as a multimodal brain cell activation marker and a role for NF-IL6 for differential brain activity. In addition, the nutritional status, as reflected by circulating levels of the cytokine-like hormone leptin, influence immune-to-brain communication and age-dependent changes in LPS-induced fever. Overall, transcription factors remain therapeutically important targets for the treatment of brain-inflammation and fever induction during infectious/non-infectious inflammatory and psychological stress. However, the exact physiological role and significance of these transcription factors requires to be further investigated.

  16. Combination of recombinant factor VIIa and fibrinogen corrects clot formation in primary immune thrombocytopenia at very low platelet counts

    DEFF Research Database (Denmark)

    Larsen, Ole H; Stentoft, Jesper; Radia, Deepti

    2013-01-01

    Haemostatic treatment modalities alternative to platelet transfusion are desirable to control serious acute bleeds in primary immune thrombocytopenia (ITP). This study challenged the hypothesis that recombinant activated factor VII (rFVIIa) combined with fibrinogen concentrate may correct whole b...

  17. Timeliness of Childhood Primary Immunization and Risk Factors Related with Delays: Evidence from the 2014 Zhejiang Provincial Vaccination Coverage Survey

    Directory of Open Access Journals (Sweden)

    Yu Hu

    2017-09-01

    Full Text Available Background: this study aimed to assess both immunization coverage and timeliness, as well as reasons for non-vaccination, and identity the risk factors of delayed immunization, for the vaccines scheduled during the first year of life, in Zhejiang province, east China. Methods: A cluster survey among children aged 24–35 months was conducted. Demographic information and socio-economic characteristics of the selected child, the mother, and the household were collected. Immunization data were transcribed from immunization cards. Timeliness was assessed with Kaplan–Meier analysis for each vaccine given before 12 months of age, based on the time frame stipulated by the expanded program on immunization of China. Cox proportional hazard regression was applied to identify risk factors of delayed immunization. Results: A total of 2772 eligible children were surveyed. The age-appropriate coverage ranged from 25.4% (95% CI: 23.7–27.0% for Bacillus Calmette–Guerin (BCG to 91.3% (95% CI: 90.2–92.3% for the first dose of oral poliomyelitis vaccine (OPV1. The most frequent reason for non-vaccination was parent’s fear of adverse events of immunization. Delayed immunizations were associated with mother having a lower education level, mother having a job, delivery at home, increasing number of children per household, and having a lower household income. Conclusions: Although the timeliness of immunization has improved since 2011, necessary steps are still needed to achieve further improvement. Timeliness of immunization should be considered as another important indicator of expanded program on immunization (EPI performance. Future interventions on vaccination coverage should take into consideration demographic and socio-economic risk factors identified in this study. The importance of adhering to the recommended schedule should be explained to parents.

  18. Activating killer-cell immunoglobulin-like receptors (KIR) and their cognate HLA ligands are significantly increased in autism.

    Science.gov (United States)

    Torres, Anthony R; Westover, Jonna B; Gibbons, Cole; Johnson, Randall C; Ward, David C

    2012-10-01

    Killer-cell immunoglobulin-like receptor (KIR) proteins are expressed on natural killer (NK) cells and appear important in innate and adaptive immunity. There are about 14 KIR genes on chromosome 19q13.4, composed of those that inhibit and those that activate NK cell killing. Haplotypes have different combinations of these genes meaning that not all genes are present in a subject. There are two main classes of cognate human leukocyte antigen (HLA) ligands (HLA-Bw4 and HLA-C1/C2) that bind to the inhibitory/activating receptors. As a general rule, the inhibitory state is maintained except when virally infected or tumor cells are encountered; however, both increased activation and inhibition states have been associated with susceptibility and protection against numerous disease states including cancer, arthritis, and psoriasis. Utilizing DNA from 158 Caucasian subjects with autism and 176 KIR control subjects we show for the first time a highly significant increase in four activating KIR genes (2DS5, 3DS1, 2DS1 and 2DS4) as measured by chi square values and odds ratios. In addition, our data suggests a highly significant increase in the activating KIR gene 2DS1 and its cognate HLA-C2 ligand (2DS1+C2; p = 0.00003 [Odds ratio = 2.87]). This information ties together two major immune gene complexes, the human leukocyte complex and the leukocyte receptor complex, and may partially explain immune abnormalities observed in many subjects with autism.

  19. Effect on liver function, immune function and inflammatory factors of laparoscopic and open cholecystectomy in patients

    Institute of Scientific and Technical Information of China (English)

    Lun Yu; Jun Zhang; Yong Jiao; Peng Yong

    2016-01-01

    Objective:To observe the effect on liver function, immune function and inflammatory factors of laparoscopic and open cholecystectomy in patients.Methods:A total of 113 patients who would experience cholecystectomy were chosen as research objects. According to their own willingness, these patients were randomly divided into LC group (67 cases) and OC group (46 cases). LC group was treated with laparoscopic cholecystectomy (LC). OC group was treated with traditional open cholecystectomy (OC). Changes of liver function (ALT, AST,γ-GT, ALP, TBIL), immune function (IgA, IgM, CD3, CD4, CD8) and inflammatory factors (CRP, IL-6, IL-8) were observed 1 and 7 d after surgery.Results: Comparison of liver function: exceptγ-GT showed no significant difference before and after surgery, the levels of ALT, AST and TBIL were significantly increased, while the level of ALP was significantly decreased 1 d after surgery in the two groups (P<0.05); the levels of ALT, AST, TBIL and ALP 7 d after surgery were comparable with preoperative levels in the two groups; furthermore, there were no significant differences referring to these indexes between the two groups at the same time points, say, 1 and 7 d after surgery. Comparison of immune function: the levels of CD3 and CD4 were significantly decreased 1 d after surgery compared with before surgery in the two groups (P<0.05); but 7 d after surgery, the levels of CD3 and CD4 were comparable with preoperative levels in the two groups; furthermore, there were no significant differences referring to the levels of CD3 and CD4 between the two groups at the same time points; As for the levels of IgA, IgM and CD8, no significant changes were observed in the two groups before and after surgery. Comparison of inflammatory factors: the levels of CRP, IL-6 and IL-8 were significantly increased 1 d after surgery compared with before surgery in the two groups (P<0.05); these mentioned levels of inflammatory factors 7 d after surgery were still higher

  20. Factors influencing gastrointestinal tract and microbiota immune interaction in preterm infants.

    Science.gov (United States)

    Collado, María Carmen; Cernada, María; Neu, Josef; Pérez-Martínez, Gaspar; Gormaz, María; Vento, Máximo

    2015-06-01

    The role of microbial colonization is indispensable for keeping a balanced immune response in life. However, the events that regulate the establishment of the microbiota, their timing, and the way in which they interact with the host are not yet fully understood. Factors such as gestational age, mode of delivery, environment, hygienic measures, and diet influence the establishment of microbiota in the perinatal period. Environmental microbes constitute the most important group of exogenous stimuli in this critical time frame. However, the settlement of a stable gut microbiota in preterm infants is delayed compared to term infants. Preterm infants have an immature gastrointestinal tract and immune system which predisposes to infectious morbidity. Neonatal microbial dynamics and alterations in early gut microbiota may precede and/or predispose to diseases such as necrotizing enterocolitis (NEC), late-onset sepsis or others. During this critical period, nutrition is the principal contributor for immunological and metabolic development, and microbiological programming. Breast milk is a known source of molecules that act synergistically to protect the gut barrier and enhance the maturation of the gut-related immune response. Host-microbe interactions in preterm infants and the protective role of diet focused on breast milk impact are beginning to be unveiled.

  1. Polyprenols as possible factors that determine an instructive role of the innate immunity in the acquired immune response.

    Science.gov (United States)

    Pronin, Alexander V; Grigorieva, Ekaterina A; Sanin, Alexander V; Narovlyansky, Alexander N; Ozherelkov, Sergei V; Deyeva, Anna V; Danilov, Leonid L; Maltsev, Sergei D; Najid, Abderrahim

    2002-07-01

    Polyprenols are an integral part of all living cells including prokaryotic and eukaryotic ones. These compounds take part in biosynthesis of glycoproteins. We have found that phosphates of polyprenols may act as effective antiviral agents with a wide spectrum of activity. One of such antiviral agents received from Pinus sativum polyprenols was named phosprenyl. Earlier we showed that phosprenyl expressed direct antiviral effect, while having mild immunomodulatory activity. In the present study we further evaluated influence of phosprenyl on the immune system. The drug was found to inhibit an early phase of IL-1 and Con A interaction in spleen cells as well as lypoxigenase activity and expression of IL-2 receptors. At the same time, phosprenyl induced NK cell activity and early TNF-alpha production. Basing on all these data we proposed that polyprenols could be considered as a "label" which grants a possibility to the innate immune system to recognize infection at the early stages and govern the acquired immunity.

  2. The hemodynamics of human septic shock relate to circulating innate immunity factors.

    Science.gov (United States)

    Hartemink, Koen J; Groeneveld, A B Johan

    2010-01-01

    The role of innate immunity, e.g., complement activation and cytokine release in the hemodynamic alterations in the course of human septic shock is largely unknown. We prospectively studied 14 consecutive septic shock patients with a pulmonary artery catheter in place. For 3 days after admission, hemodynamic variables and plasma levels of C3a, a product of complement activation, and interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) were measured 6-hourly. Doses of vasoactive drugs were recorded. Of the 14 patients, 8 died in the ICU. Patients had a hyperdynamic circulation with tachycardia, mild hypotension, increased cardiac index, peripheral vasodilation and myocardial depression. C3a, IL-6 and TNF-α plasma levels were supranormal in 123 of 138 (89%), 132 of 138 (96%) and 83 of 111 (75%) measurements, respectively. Independently of blood culture results, treatment with vasoactive drugs and outcome, mean arterial blood pressure and systemic vascular resistance index were lower when IL-6 levels were higher and left ventricular function was less depressed when C3a levels were higher in the course of septic shock. The TNF-α levels did not invariably relate to peripheral vascular and myocardial function parameters. Our serial observations suggest that, in human septic shock, peripheral vasodilation is most strongly and independently, of all inflammatory factors, associated with IL-6 release, whereas complement activation partly offsets the myocardial depression of the syndrome. Innate immunity factors may thus differ in their contribution to the course of hemodynamic abnormalities of septic shock.

  3. Novel Immunity Proteins Associated with Colicin M-like Bacteriocins Exhibit Promiscuous Protection in Pseudomonas

    Science.gov (United States)

    Ghequire, Maarten G. K.; Kemland, Lieselore; De Mot, René

    2017-01-01

    Bacteriocins related to colicin M, acting via cleavage of the cell wall precursor lipid II, have been characterized in γ- and β-proteobacteria. Depending on the species, immunity is provided by either an inner membrane-anchored periplasmic protein or by an integral membrane protein. In Pseudomonas however, the immunity partner of colicin M-like bacteriocins remains unknown. Based on an in silico analysis in pseudomonad genomes, we here identify a gene encoding a putative immunity partner that represents a novel type of integral membrane protein (PmiA, Pseudomonas colicin M-like immunity type A). By heterologous expression of pmiA genes in susceptible strains, we show that immunity to colicin M-like bacteriocins is indeed provided by the cognate PmiA. Sequence homology among PmiA proteins is essentially absent, except for a short motif with a conserved periplasm-exposed aspartate residue. However, PmiA's protective function is not abolished by changing this acidic residue to the uncharged alanine. Immunity by PmiAs appears promiscuous to the extent that PmiA homologs from a clade sharing bacteriocin linked to the original PmiA. This study shows that multiple immunity factors have evolved independently to silence lipid II-targeting enzymatic bacteriocins. Their relaxed bacteriocin immunization capacity contrasts to the strict specificity of immunity proteins shielding the enzymatic domain of nuclease bacteriocins. The nature of associated immune functions needs consideration when using such natural protein antibiotics or designing novel variants. PMID:28194143

  4. Neutrophil Recruitment by Tumor Necrosis Factor from Mast Cells in Immune Complex Peritonitis

    Science.gov (United States)

    Zhang, Yan; Ramos, Bernard F.; Jakschik, Barbara A.

    1992-12-01

    During generalized immune complex-induced inflammation of the peritoneal cavity, two peaks of tumor necrosis factor (TNF) were observed in the peritoneal exudate of normal mice. In mast cell-deficient mice, the first peak was undetected, and the second peak of TNF and neutrophil influx were significantly reduced. Antibody to TNF significantly inhibited neutrophil infiltration in normal but not in mast cell-deficient mice. Mast cell repletion of the latter normalized TNF, neutrophil mobilization, and the effect of the antibody to TNF. Thus, in vivo, mast cells produce the TNF that augments neutrophil emigration.

  5. Etiology of Waldenström macroglobulinemia: genetic factors and immune-related conditions.

    Science.gov (United States)

    Manasanch, Elisabet E; Kristinsson, Sigurdur Y; Landgren, Ola

    2013-04-01

    Epidemiologic studies provide an insight into the etiology of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, which indicates that repetitive immune stimulation and genetic factors play an important role. Here, the current understanding on the causes of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia are reviewed. Recent studies of the literature are discussed, and future population-based studies are proposed to further elucidate the molecular mechanisms that underlie these associations. Finally, the clinical implications of these data are outlined, and perspectives on clinical follow-up and counseling are provided.

  6. Immune-Pineal Axis: Nuclear Factor κB (NF-kB Mediates the Shift in the Melatonin Source from Pinealocytes to Immune Competent Cells

    Directory of Open Access Journals (Sweden)

    Regina P. Markus

    2013-05-01

    Full Text Available Pineal gland melatonin is the darkness hormone, while extra-pineal melatonin produced by the gonads, gut, retina, and immune competent cells acts as a paracrine or autocrine mediator. The well-known immunomodulatory effect of melatonin is observed either as an endocrine, a paracrine or an autocrine response. In mammals, nuclear translocation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB blocks noradrenaline-induced melatonin synthesis in pinealocytes, which induces melatonin synthesis in macrophages. In addition, melatonin reduces NF-κB activation in pinealocytes and immune competent cells. Therefore, pathogen- or danger-associated molecular patterns transiently switch the synthesis of melatonin from pinealocytes to immune competent cells, and as the response progresses melatonin inhibition of NF-κB activity leads these cells to a more quiescent state. The opposite effect of NF-κB in pinealocytes and immune competent cells is due to different NF-κB dimers recruited in each phase of the defense response. This coordinated shift of the source of melatonin driven by NF-κB is called the immune-pineal axis. Finally, we discuss how this concept might be relevant to a better understanding of pathological conditions with impaired melatonin rhythms and hope it opens new horizons for the research of side effects of melatonin-based therapies.

  7. Global importation and population risk factors for measles in New Zealand: a case study for highly immunized populations.

    Science.gov (United States)

    Hayman, D T S; Marshall, J C; French, N P; Carpenter, T E; Roberts, M G; Kiedrzynski, T

    2017-07-01

    As endemic measles is eliminated through immunization, countries must determine the risk factors for the importation of measles into highly immunized populations to target control measures. Despite eliminating endemic measles, New Zealand suffers from outbreaks after introductions from abroad, enabling us to use it as a model for measles introduction risk. We used a generalized linear model to analyze risk factors for 1137 measles cases from 2007 to June 2014, provide estimates of national immunity levels, and model measles importation risk. People of European ethnicity made up the majority of measles cases. Age is a positive risk factor, particularly 0-2-year-olds and 5-17-year-old Europeans, along with increased wealth. Pacific islanders were also at greater risk, but due to 0-2-year-old cases. Despite recent high measles, mumps, and rubella vaccine immunization coverage, overall population immunity against measles remains ~90% and is lower in people born between 1982 and 2005. Greatest measles importation risk is during December, and countries predicted to be sources have historical connections and highest travel rates (Australia and UK), followed by Asian countries with high travel rates and higher measles incidences. Our results suggest measles importation due to travel is seeding measles outbreaks, and immunization levels are insufficient to continue to prevent outbreaks because of heterogeneous immunity in the population, leaving particular age groups at risk.

  8. Myeloid leukemia factor functions in anti-WSSV immune reaction of kuruma shrimp, Marsupenaeus japonicus.

    Science.gov (United States)

    Feng, Xiao-Wu; Huo, Li-Jie; Sun, Jie-Jie; Xu, Ji-Dong; Niu, Guo-Juan; Wang, Jin-Xing; Shi, Xiu-Zhen

    2017-09-12

    Myeloid leukemia factor (MLF) plays an important role in development, cell cycle, myeloid differentiation, and regulates the RUNX transcription factors. However, the function of MLF in immunity is still unclear. In this study, an MLF was identified and characterized in kuruma shrimp Marsupenaeus japonicus, and named as MjMLF. The full-length cDNA of MjMLF contained 1111 nucleotides, which had an opening reading frame of 816 bp encoding a protein of 272 amino acids with an MLF1-interacting protein domain. MjMLF could be ubiquitously detected in different tissues of shrimp at the transcriptional level. The expression pattern analysis showed that MjMLF could be upregulated in shrimp hemocytes and hepatopancreas after white spot syndrome virus challenge. The RNA interference and protein injection assay showed that MjMLF could inhibit WSSV replication in vivo. Flow cytometry assay showed that MjMLF could induce hemocytes apoptosis which functioned in the shrimp antiviral reaction. All the results suggested that MjMLF played an important role in the antiviral immune reaction of kuruma shrimp. The research indicated that MjMLF might function as a novel regulator to inhibit WSSV replication in shrimp. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Risk factors for poor immune response to influenza vaccination in elderly people

    Directory of Open Access Journals (Sweden)

    N.C.J. Bellei

    2006-08-01

    Full Text Available Influenza vaccination of elderly people is efficacious and cost effective for the prevention of influenza and its complications. Some studies have pointed out low immunogenicity in this group. Health status has been poorly investigated as a risk factor that may influence the immune response to influenza vaccine. We established an immunization response study of a highly-matched elderly population in a nursing home. One-hundred-twenty subjects of Ashkenazian origin had their vaccine-induced antibody response assessed. Good response was obtained in 30.8% (37/120, and 31.7% (38/120 did not react. A lack of good response was found to be associated with dementia (P=0.016 in a multivariate analysis. In addition to dementia, malnutrition was frequently observed among poor responders, suggesting that these factors should be considered in vaccination studies. Chemoprophylaxis in addition to vaccination for elderly presenting dementia should be considered, particularly for those people living nursing homes.

  10. Does bilingualism change native-language reading? Cognate effects in a sentence context.

    Science.gov (United States)

    Van Assche, Eva; Duyck, Wouter; Hartsuiker, Robert J; Diependaele, Kevin

    2009-08-01

    Becoming a bilingual can change a person's cognitive functioning and language processing in a number of ways. This study focused on how knowledge of a second language influences how people read sentences written in their native language. We used the cognate-facilitation effect as a marker of cross-lingual activations in both languages. Cognates (e.g., Dutch-English schip [ship]) and controls were presented in a sentence context, and eye movements were monitored. Results showed faster reading times for cognates than for controls. Thus, this study shows that one of people's most automated skills, reading in one's native language, is changed by the knowledge of a second language.

  11. Immune modulation associated with vascular endothelial growth factor (VEGF) blockade in patients with glioblastoma.

    Science.gov (United States)

    Thomas, Alissa A; Fisher, Jan L; Hampton, Thomas H; Christensen, Brock C; Tsongalis, Gregory J; Rahme, Gilbert J; Whipple, Chery A; Steel, Sandra E; Davis, Melissa C; Gaur, Arti B; Lewis, Lionel D; Ernstoff, Marc S; Fadul, Camilo E

    2017-03-01

    Vascular endothelial growth factor (VEGF), in addition to being pro-angiogenic, is an immunomodulatory cytokine systemically and in the tumor microenvironment. We previously reported the immunomodulatory effects of radiation and temozolomide (TMZ) in newly diagnosed glioblastoma. This study aimed to assess changes in peripheral blood mononuclear cell (PBMC) populations, plasma cytokines, and growth factor concentrations following treatment with radiation, TMZ, and bevacizumab (BEV). Eleven patients with newly diagnosed glioblastoma were treated with radiation, TMZ, and BEV, following surgery. We measured immune-related PBMC subsets using multi-parameter flow cytometry and plasma cytokine and growth factor concentrations using electrochemiluminescence-based multiplex analysis at baseline and after 6 weeks of treatment. The absolute number of peripheral blood regulatory T cells (Tregs) decreased significantly following treatment. The lower number of peripheral Tregs was associated with a CD4+ lymphopenia, and thus, the ratio of Tregs to PBMCs was unchanged. The addition of bevacizumab to standard radiation and temozolomide led to the decrease in the number of circulating Tregs when compared with our prior study. There was a significant decrease in CD8+ cytotoxic and CD4+ recent thymic emigrant T cells, but no change in the number of myeloid-derived suppressor cells. Significant increases in plasma VEGF and placental growth factor (PlGF) concentrations were observed. Treatment with radiation, TMZ, and BEV decreased the number but not the proportion of peripheral Tregs and increased the concentration of circulating VEGF. This shift in the peripheral immune cell profile may modulate the tumor environment and have implications for combining immunotherapy with anti-angiogenic therapy.

  12. Immune factors and fatty acid composition in human milk from river/lake, coastal and inland regions of China.

    Science.gov (United States)

    Urwin, Heidi J; Zhang, Jian; Gao, Yixiong; Wang, Chunrong; Li, Lixiang; Song, Pengkun; Man, Qingqing; Meng, Liping; Frøyland, Livar; Miles, Elizabeth A; Calder, Philip C; Yaqoob, Parveen

    2013-06-01

    Breast milk fatty acid composition may be affected by the maternal diet during gestation and lactation. The influence of dietary and breastmilk fatty acids on breast milk immune factors is poorly defined. We determined the fatty acid composition and immune factor concentrations of breast milk from women residing in river/lake, coastal and inland regions of China, which differ in their consumption of lean fish and oily fish. Breast milk samples were collected on days 3–5 (colostrum), 14 and 28 post-partum (PP) and analysed for soluble CD14 (sCD14), transforming growth factor (TGF)-b1, TGF-b2, secretory IgA (sIgA) and fatty acids. The fatty acid composition of breast milk differed between the regions and with time PP. The concentrations of all four immune factors in breast milk decreased over time, with sCD14, sIgA and TGF-b1 being highest in the colostrum in the river and lake region. Breast milk DHA and arachidonic acid (AA) were positively associated, and g-linolenic acid and EPA negatively associated, with the concentrations of each of the four immune factors. In conclusion, breast milk fatty acids and immune factors differ between the regions in China characterised by different patterns of fish consumption and change during the course of lactation. A higher breast milk DHA and AA concentration is associated with higher concentrations of immune factors in breast milk, suggesting a role for these fatty acids in promoting gastrointestinal and immune maturation of the infant.

  13. Effects of indomethacin suppositories on serum amylase, inflammatory factors and immune function after endoscopic retrograde cholangiopancreatography

    Institute of Scientific and Technical Information of China (English)

    Xiao-Bin Peng; Xiao-Yun Wang; Gao-Jue Wu; Zhen Hu; Shuang Tang; Lei Gong

    2016-01-01

    Objective:To explore the effects of indomethacin suppositories on serum amylase, inflammatory factors and immune function after endoscopic retrograde cholangiopancreatography (ERCP).Methods:A total of 85 patients with common bile duct stones or obstructive jaundice were divided into the observation group (n=45) and the control group (n=40) according to the different treatment methods, both two groups patients were treated with ERCP, patients in the observation group was given indomethacin suppositories 50 mg preoperative 30 min. Serum amylase, inflammatory factors and T cell subsets were detected preoperative, postoperative 6h and postoperative 24h. Inflammatory factors including interleukin -10 (IL-10), interleukin -6 (IL-6), tumor necrosis factor alpha (TNF-α) and interleukin-4 (IL-4). T cell subsets including CD3+, CD4+, CD8+ and calculated CD4+/CD8+.Results:In both two groups, postoperative 6h, 24h serum amylase were significantly higher than before surgery; in the observation group, the postoperative 6h, 24h serum amylase were significantly lower than in the control group at the same time point and the differences were statistically significant (P<0.05). Both two groups’ postoperative 6h, 24h serum pro-inflammatory factor IL-6 and TNF-α increased first and then decreased, both were significantly higher than before surgery; both two groups’ postoperative 6h, 24h serum anti-inflammatory factor IL-10 and IL-4 gradually increased, both were significantly higher than before surgery, and the differences were statistically significant (P<0.05); In the observation group, anti-inflammatory factor IL-10 and IL-4 significantly increased while pro-inflammatory factor IL-6 and TNF-α significantly decreased compared with the control group at the same time point 6h and 24h after surgery, the difference between the two groups was statistically significant (P<0.05). Both two groups’ postoperative 6h, 24h T cell subsets CD3+, CD4+, CD4+/CD8+first decreased and then

  14. Sustained Partial Sleep Deprivation: Effects on Immune Modulation and Growth Factors

    Science.gov (United States)

    Mullington, Janet M.

    1999-01-01

    from this larger study: a 4.2 hour per night condition, and a 8.2 hour per night condition. During space flight, muscle mass and bone density are reduced, apparently due to loss of GH and IGF-I, associated with microgravity. Since >70% of growth hormone (GH) is secreted at night in normal adults, we hypothesized that the chronic sleep restriction to 4 hours per night would reduce GH levels as measured in the periphery. In this synergy project, in collaboration with the "Muscle Alterations and Atrophy Team ", we are measuring insulin-like growth factor-I (IGF-I) in peripheral circulation to test the prediction that it will be reduced by chronic sleep restriction. In addition to stress modulation of immune function, recent research suggests that sleep is also involved. While we all have the common experience of being sleepy when suffering from infection, and being susceptible to infection when not getting enough sleep, the mechanisms involved in this process are not understood and until recently have gone largely overlooked. We believe that the immune function changes seen in spaceflight may also be related to the cumulative effects of sleep loss. Moreover, in space flight, the possibility of compromised immune function or of the reactivation of latent viruses are serious potential hazards for the success of long term missions. Confined living conditions, reduced sleep, altered diet and stress are all factors that may compromise immune function, thereby increasing the risks of developing and transmitting disease. Medical complications, which would not pose serious problems on earth, may be disastrous if they emerged in space.

  15. Humoral immune response to HTLV-1 basic leucine zipper factor (HBZ in HTLV-1-infected individuals

    Directory of Open Access Journals (Sweden)

    Enose-Akahata Yoshimi

    2013-02-01

    Full Text Available Abstract Background Human T cell lymphotropic virus type 1 (HTLV-1 infection can lead to development of adult T cell leukemia/lymphoma (ATL or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP in a subset of infected subjects. HTLV-1 basic leucine zipper factor (HBZ gene has a critical role in HTLV-1 infectivity and the development of ATL and HAM/TSP. However, little is known about the immune response against HBZ in HTLV-1-infected individuals. In this study, we examined antibody responses against HBZ in serum/plasma samples from 436 subjects including HTLV-1 seronegative donors, asymptomatic carriers (AC, ATL, and HAM/TSP patients using the luciferase immunoprecipitation system. Results Immunoreactivity against HBZ was detected in subsets of all HTLV-1-infected individuals but the test did not discriminate between AC, ATL and HAM/TSP. However, the frequency of detection of HBZ-specific antibodies in the serum of ATL patients with the chronic subtype was higher than in ATL patients with the lymphomatous subtype. Antibody responses against HBZ were also detected in cerebrospinal fluid of HAM/TSP patients with anti-HBZ in serum. Antibody responses against HBZ did not correlate with proviral load and HBZ mRNA expression in HAM/TSP patients, but the presence of an HBZ-specific response was associated with reduced CD4+ T cell activation in HAM/TSP patients. Moreover, HBZ-specific antibody inhibited lymphoproliferation in the PBMC of HAM/TSP patients. Conclusions This is the first report demonstrating humoral immune response against HBZ associated with HTLV-I infection. Thus, a humoral immune response against HBZ might play a role in HTLV-1 infection.

  16. Pre-transplant immune factors may be associated with BK polyomavirus reactivation in kidney transplant recipients.

    Science.gov (United States)

    DeWolfe, David; Gandhi, Jinal; Mackenzie, Matthew R; Broge, Thomas A; Bord, Evelyn; Babwah, Amaara; Mandelbrot, Didier A; Pavlakis, Martha; Cardarelli, Francesca; Viscidi, Raphael; Chandraker, Anil; Tan, Chen S

    2017-01-01

    BK polyomavirus (BKPyV) reactivation in kidney transplant recipients can lead to allograft damage and loss. The elements of the adaptive immune system that are permissive of reactivation and responsible for viral control remain incompletely described. We performed a prospective study evaluating BKPyV-specific T-cell response, humoral response and overall T-cell phenotype beginning pre-transplant through one year post-transplant in 28 patients at two centers. We performed an exploratory analysis of risk factors for the development of viremia and viruria as well as compared the immune response to BKPyV in these groups and those who remained BK negative. 6 patients developed viruria and 3 developed viremia. BKPyV-specific CD8+ T-cells increased post-transplant in viremic and viruric but not BK negative patients. BKPyV-specific CD4+ T-cells increased in viremic, but not viruric or BK negative patients. Anti-BKPyV IgG antibodies increased in viruric and viremic patients but remained unchanged in BK negative patients. Viremic patients had a greater proportion of CD8+ effector cells pre-transplant and at 12 months post-transplant. Viremic patients had fewer CD4+ effector memory cells at 3 months post-transplant. Exploratory analysis demonstrated lower CD4 and higher total CD8 proportions, higher anti-BKPyV antibody titers and the cause of renal failure were associated BKPyV reactivation. In conclusion, low CD4, high CD8 and increased effector CD8 cells were found pre-transplant in patients who became viremic, a phenotype associated with immune senescence. This pre-transplant T-cell senescence phenotype could potentially be used to identify patients at increased risk of BKPyV reactivation.

  17. The dorsal-related immunity factor, Dif, is a sequence-specific trans-activator of Drosophila Cecropin gene expression.

    OpenAIRE

    Petersen, U M; Björklund, G; Ip, Y T; Engström, Y

    1995-01-01

    A new member of the Rel family of transcription factors, the dorsal-related immunity factor, Dif, was recently cloned and suggested to be involved in regulating the immune response in Drosophila. Despite its classification as a Rel family member, the Dif cDNA-encoded product has not been proven previously to be a transcription factor. We now present evidence that the Dif gene product trans-activates the Drosophila Cecropin A1 gene in co-transfection assays. The transactivation requires a 40 b...

  18. Selected Factors of Innate Immunity in Healthy Individuals with S. aureus Nasal Carriage.

    Science.gov (United States)

    Karpiński, Tomasz M; Żaba, Zbigniew; Chudzicka-Strugała, Izabela; Szkaradkiewicz, Anna K; Jaworska, Agata; Zeidler, Agnieszka; Andrzejewska, Ewa; Szkaradkiewicz, Andrzej

    2016-01-01

    Nasal carriage of Staphylococcus aureus represents a well-defined factor of risk involving community and hospital-acquired infections. Recently a significance of several host factors has been pointed out and, in particular, of immune determinants in nasal S. aureus colonization. Therefore, this study aimed at analysis of manifestation involving manifestation in the nasal secretions of important components of the host innate immunity - human beta-defensin-2 (HBD-2), lysozyme (Ly), and interferon-gamma (IFN-γ) in healthy individuals and in persons with persistent carriage of S. aureus. The studies were conducted in two groups of healthy volunteers, encompassing non-carriers (group 1) or persistent carriers of S. aureus (group 2). Elisa assays were employed to evaluate levels of HBD-2, Ly, and IFN-γ in nasal secretions of the examined donors. In S. aureus carriers a significant variability of HBD-2 levels was detected, corresponding to, respectively, the high (averaging at 1.46 ng/ml) and the low (averaging at 0.13 ng/ml) secretory response of the defensin. The level of Ly in S. aureus carriers averaged at 1.46 μg/ml and it manifested no significant difference as compared to that noted in non-carriers. In turn, concentrations of IFN-γ in nasal secretions in the group of carriers of S. aureus amounted on the average to 81.7 pg/ml and they were 1.3-fold higher that in the group of non-carriers. The obtained results allow to conclude that IFN-γ secretion by the nasal cavity-colonizing S. aureus remains quantitatively insufficient to eliminate the pathogen. Nevertheless, a significant increase in levels of this host factor may be important for restriction of the staphylococcal colonization and protection against development of an invasive infection. In turn, the role of HBD-2 and Ly in inactivation of the colonizing S. aureus remains doubtful.

  19. Recognition of Cognate Transfer RNA by the 30S Ribosomal Subunit

    Energy Technology Data Exchange (ETDEWEB)

    Ogle, James M.; Brodersen, Ditlev E.; Clemons, William M.; Tarry, Michael J.; Carter, Andrew P.; Ramakrishnan, V. (MRC Laboratory of Molecular Biology)

    2009-10-07

    Crystal structures of the 30S ribosomal subunit in complex with messenger RNA and cognate transfer RNA in the A site, both in the presence and absence of the antibiotic paromomycin, have been solved at between 3.1 and 3.3 angstroms resolution. Cognate transfer RNA (tRNA) binding induces global domain movements of the 30S subunit and changes in the conformation of the universally conserved and essential bases A1492, A1493, and G530 of 16S RNA. These bases interact intimately with the minor groove of the first two base pairs between the codon and anticodon, thus sensing Watson-Crick base-pairing geometry and discriminating against near-cognate tRNA. The third, or 'wobble,' position of the codon is free to accommodate certain noncanonical base pairs. By partially inducing these structural changes, paromomycin facilitates binding of near-cognate tRNAs.

  20. Ataluren stimulates ribosomal selection of near-cognate tRNAs to promote nonsense suppression

    National Research Council Canada - National Science Library

    Roy, Bijoyita; Friesen, Westley J; Tomizawa, Yuki; Leszyk, John D; Zhuo, Jin; Johnson, Briana; Dakka, Jumana; Trotta, Christopher R; Xue, Xiaojiao; Mutyam, Venkateshwar; Keeling, Kim M; Mobley, James A; Rowe, Steven M; Bedwell, David M; Welch, Ellen M; Jacobson, Allan

    2016-01-01

    .... Accordingly, nonsense mutations cause some of the most severe forms of inherited disorders. The small-molecule drug ataluren promotes therapeutic nonsense suppression and has been thought to mediate the insertion of near-cognate tRNAs at PTCs...

  1. A chromosomally encoded virulence factor protects the Lyme disease pathogen against host-adaptive immunity.

    Directory of Open Access Journals (Sweden)

    Xiuli Yang

    2009-03-01

    Full Text Available Borrelia burgdorferi, the bacterial pathogen of Lyme borreliosis, differentially expresses select genes in vivo, likely contributing to microbial persistence and disease. Expression analysis of spirochete genes encoding potential membrane proteins showed that surface-located membrane protein 1 (lmp1 transcripts were expressed at high levels in the infected murine heart, especially during early stages of infection. Mice and humans with diagnosed Lyme borreliosis also developed antibodies against Lmp1. Deletion of lmp1 severely impaired the pathogen's ability to persist in diverse murine tissues including the heart, and to induce disease, which was restored upon chromosomal complementation of the mutant with the lmp1 gene. Lmp1 performs an immune-related rather than a metabolic function, as its deletion did not affect microbial persistence in immunodeficient mice, but significantly decreased spirochete resistance to the borreliacidal effects of anti-B. burgdorferi sera in a complement-independent manner. These data demonstrate the existence of a virulence factor that helps the pathogen evade host-acquired immune defense and establish persistent infection in mammals.

  2. Analogue Encoding of Physicochemical Properties of Proteins in their Cognate Messenger RNAs

    OpenAIRE

    Polyansky, Anton A; Hlevnjak, Mario; Zagrovic, Bojan

    2013-01-01

    Being related by the genetic code, mRNAs and their cognate proteins exhibit mutually interdependent compositions, which implies the possibility of a direct connection between their general physicochemical properties. Here we probe the general potential of the cell to encode information about proteins in the average characteristics of their cognate mRNAs and decode it in a ribosome-independent manner. We show that average protein hydrophobicity, calculated from either sequences or 3D structure...

  3. Cognates Facilitate Word Recognition in Young Spanish-English Bilinguals' Test Performance.

    Science.gov (United States)

    Pérez, Anita Méndez; Peña, Elizabeth D; Bedore, Lisa M

    2010-01-01

    This study was conducted to determine whether bilingual children of kindergarten and first grade age were able to recognize cognates of Spanish words, and whether the ability to recognize cognates changed the score on a measure of English vocabulary. 89 bilingual children were administered all of the items on the Test of Language Development-Primary:3 (TOLD-P:3) Picture Vocabulary Subtest (Newcomer & Hammill, 1997). Parents and teachers provided information about the child's English and Spanish exposure. Data analysis using repeated measures ANOVA compared performance in bilingual children divided by level of relative exposure to Spanish and English on cognate verses noncognate items. Sensitivity to cognate status was related to the amount of language exposure. Children exposed to more Spanish knew more of the English cognates of Spanish words than children who were exposed to balanced amounts of Spanish and English and those exposed to more English. Standard scores differences on the TOLD-P:3 across all levels of Spanish-English exposure were found using ceiling rules and total raw scores. Findings suggest a transfer of vocabulary knowledge from the students' first language (Spanish) to receptive vocabulary in English. Children as early as kindergarten are sensitive to the Spanish/English cognates. Results have implications for understanding bilingual children's' performance on assessment, and for developing intervention strategies to enhance vocabulary in English language learners.

  4. RFX transcription factor DAF-19 regulates 5-HT and innate immune responses to pathogenic bacteria in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Yusu Xie

    Full Text Available In Caenorhabditis elegans the Toll-interleukin receptor domain adaptor protein TIR-1 via a conserved mitogen-activated protein kinase (MAPK signaling cascade induces innate immunity and upregulates serotonin (5-HT biosynthesis gene tph-1 in a pair of ADF chemosensory neurons in response to infection. Here, we identify transcription factors downstream of the TIR-1 signaling pathway. We show that common transcription factors control the innate immunity and 5-HT biosynthesis. We demonstrate that a cysteine to tyrosine substitution in an ARM motif of the HEAT/Arm repeat region of the TIR-1 protein confers TIR-1 hyperactivation, leading to constitutive tph-1 upregulation in the ADF neurons, increased expression of intestinal antimicrobial genes, and enhanced resistance to killing by the human opportunistic pathogen Pseudomonas aeruginosa PA14. A forward genetic screen for suppressors of the hyperactive TIR-1 led to the identification of DAF-19, an ortholog of regulatory factor X (RFX transcription factors that are required for human adaptive immunity. We show that DAF-19 concerts with ATF-7, a member of the activating transcription factor (ATF/cAMP response element-binding B (CREB family of transcription factors, to regulate tph-1 and antimicrobial genes, reminiscent of RFX-CREB interaction in human immune cells. daf-19 mutants display heightened susceptibility to killing by PA14. Remarkably, whereas the TIR-1-MAPK-DAF-19/ATF-7 pathway in the intestinal immunity is regulated by DKF-2/protein kinase D, we found that the regulation of tph-1 expression is independent of DKF-2 but requires UNC-43/Ca(2+/calmodulin-dependent protein kinase (CaMK II. Our results suggest that pathogenic cues trigger a common core-signaling pathway via tissue-specific mechanisms and demonstrate a novel role for RFX factors in neuronal and innate immune responses to infection.

  5. Social capital of Iranian patients living with acquired immune deficiency syndrome and associated factors.

    Science.gov (United States)

    Ansari, S K; Nedjat, S; Jabbari, H; Saiepour, N; Heris, M J

    2015-12-13

    This study investigated the social capital of Iranian patients living with acquired immune deficiency syndrome (AIDS) and the associated factors. In a cross-sectional study the Integrated Social Capital Questionnaire was filled by a sequential sample of 300 patients visiting a referral counselling centre in Tehran. The patients' social capital scores were around 50% in the trust, social cohesion, collective action and cooperation and political empowerment domains. The groups and networks membership domain scored the lowest (27.1%). In regression analysis, employment status was significantly associated with groups and networks membership; age, marital status and financial status were associated with collective action and cooperation; period of disease awareness and marital status affected social cohesion and inclusion; and having risky behaviour affected empowerment and political action. Efforts are needed to enhance the social capital of those patients living with AIDS who are younger, unemployed, divorced/widowed, with risky behaviours and shorter disease awareness.

  6. Circadian transcription factor BMAL1 regulates innate immunity against select RNA viruses.

    Science.gov (United States)

    Majumdar, Tanmay; Dhar, Jayeeta; Patel, Sonal; Kondratov, Roman; Barik, Sailen

    2017-02-01

    BMAL1 (brain and muscle ARNT-like protein 1, also known as MOP3 or ARNT3) belongs to the family of the basic helix-loop-helix (bHLH)-PAS domain-containing transcription factors, and is a key component of the molecular oscillator that generates circadian rhythms. Here, we report that BMAL1-deficient cells are significantly more susceptible to infection by two major respiratory viruses of the Paramyxoviridae family, namely RSV and PIV3. Embryonic fibroblasts from Bmal1(-/-) mice produced nearly 10-fold more progeny virus than their wild type controls. These results were supported by animal studies whereby pulmonary infection of RSV produced a more severe disease and morbidity in Bmal1(-/-)mice. These results show that BMAL1 can regulate cellular innate immunity against specific RNA viruses.

  7. CsBAFF, a Teleost B Cell Activating Factor, Promotes Pathogen-Induced Innate Immunity and Vaccine-Induced Adaptive Immunity.

    Directory of Open Access Journals (Sweden)

    Yun Sun

    Full Text Available B cell activating factor (BAFF is a member of the tumor necrosis factor family that is known to play an important role in B cell activation, proliferation, and differentiation in mammals. However, studies of BAFF in teleosts are very limited and its function, in particular that under in vivo conditions, is essentially unknown. In this study, we conducted in vivo as well as in vitro functional analyses of a BAFF homologue (CsBAFF from the teleost fish tongue sole (Cynoglossus semilaevis. CsBAFF is composed of 261 residues and shares moderate sequence identities with known BAFFs of other teleosts. CsBAFF expression was most abundant in immune organs and was upregulated during bacterial infection. Purified recombinant CsBAFF (rCsBAFF bound to tongue sole lymphocytes and promoted cellular proliferation and survival. The results of an in vivo study showed that CsBAFF overexpression in tongue sole significantly enhanced macrophage activation and reduced bacterial infection in fish tissues, whereas knockdown of CsBAFF expression resulted in increased bacterial dissemination and colonization in fish tissues. Furthermore, vaccination studies showed that CsBAFF enhanced the immunoprotection of a DNA vaccine and augmented the production of specific serum antibodies. Taken together, these results provide the first in vivo evidence to indicate that teleost BAFF is an immunostimulator that significantly contributes to the innate antibacterial immune response and vaccine-induced adaptive immune response.

  8. The Mesenchymal Precursor Cell Marker Antibody STRO-1 Binds to Cell Surface Heat Shock Cognate 70.

    Science.gov (United States)

    Fitter, Stephen; Gronthos, Stan; Ooi, Soo Siang; Zannettino, Andrew C W

    2016-12-27

    Since its discovery more than 25 years ago, the STRO-1 antibody has played a fundamental role in defining the hierarchical nature of mesenchymal precursor cells (MPC) and their progeny. STRO-1 antibody binding remains a hallmark of immature pluripotent MPC. Despite the significance of STRO-1 in the MPC field, the identity of the antigen has remained elusive. Using a combination of two-dimensional gel electrophoresis, coupled with Western blotting and Tandem mass spectroscopy, we have identified the STRO-1 antigen as heat shock cognate 70 (HSC70;HSPA8). STRO-1 binds to immune-precipitated HSC70 and siRNA-mediated knock down of HSPA8 reduced STRO-1 binding. STRO-1 surface binding does not correlate with HSC70 expression and sequestration of cholesterol reduces STRO-1 surface binding, suggesting that the plasma membrane lipid composition may be an important determinant in the presentation of HSC70 on the cell surface. HSC70 is present on the surface of STRO-1(+) but not STRO-1(-) cell lines as assessed by cell surface biotinylation and recombinant HSC70 blocks STRO-1 binding to the cell surface. The STRO-1 epitope on HSC70 was mapped to the ATPase domain using a series of deletion mutants in combination with peptide arrays. Deletion of the first four amino acids of the consensus epitope negated STRO-1 binding. Notably, in addition to HSC70, STRO-1 cross-reacts with heat shock protein 70 (HSP70), however all the clonogenic cell activity is restricted to the STRO-1(BRIGHT) /HSP70(-) fraction. These results provide important insight into the properties that define multipotent MPC and provide the impetus to explore the role of cell surface HSC70 in MPC biology. Stem Cells 2016.

  9. Immune modulation and increased neurotrophic factor production in multiple sclerosis patients treated with testosterone

    Directory of Open Access Journals (Sweden)

    Giesser Barbara S

    2008-07-01

    Full Text Available Abstract Background Multiple sclerosis is a chronic inflammatory disease of the central nervous system with a pronounced neurodegenerative component. It has been suggested that novel treatment options are needed that target both aspects of the disease. Evidence from basic and clinical studies suggests that testosterone has an immunomodulatory as well as a potential neuroprotective effect that could be beneficial in MS. Methods Ten male MS patients were treated with 10 g of gel containing 100 mg of testosterone in a cross-over design (6 month observation period followed by 12 months of treatment. Blood samples were obtained at three-month intervals during the observation and the treatment period. Isolated blood peripheral mononuclear cells (PBMCs were used to examine lymphocyte subpopulation composition by flow cytometry and ex vivo protein production of cytokines (IL-2, IFNγ, TNFα, IL-17, IL-10, IL-12p40, TGFβ1 and growth factors (brain-derived neurotrophic factor BDNF, platelet-derived growth factor PDGF-BB, nerve growth factor NGF, and ciliary neurotrophic factor CNTF. Delayed type hypersensitivity (DTH skin recall tests were obtained before and during treatment as an in vivo functional immune measure. Results Testosterone treatment significantly reduced DTH recall responses and induced a shift in peripheral lymphocyte composition by decreasing CD4+ T cell percentage and increasing NK cells. In addition, PBMC production of IL-2 was significantly decreased while TGFβ1 production was increased. Furthermore, PBMCs obtained during the treatment period produced significantly more BDNF and PDGF-BB. Conclusion These results are consistent with an immunomodulatory effect of testosterone treatment in MS. In addition, increased production of BDNF and PDGF-BB suggests a potential neuroprotective effect. Trial Registration NCT00405353 http://www.clinicaltrials.gov

  10. Toll-like receptors and interferon associated immune factors in viral haemorrhagic septicaemia virus-infected olive flounder (Paralichthys olivaceus).

    Science.gov (United States)

    Avunje, Satheesha; Kim, Wi-Sik; Park, Chang-Su; Oh, Myung-Joo; Jung, Sung-Ju

    2011-09-01

    Pattern recognition receptor (PRR) toll-like receptors (TLRs), antiviral agent interferon (IFN) and the effector IFN stimulated genes (ISGs) play pivotal role in antiviral innate immunity of a host. The present in-vivo experiment was conducted to investigate the role of these innate immune factors in early phase as well as during recovery of viral haemorrhagic septicaemia virus (VHSV) infection by quantitative real-time reverse transcriptase polymerase chain reaction. A less lethal VHSV infection was generated in olive flounder (Paralichthys olivaceus) and was sampled at 3, 6, and 12h post infection (hpi), and 1, 2, 4, and 7 days post infection (dpi). At 3 hpi, the VHSV N gene was detected in three out of five fish and all five fish showed a relative fold increase of TLR 2, TLR 7, interleukin 8 (IL 8), IFN regulatory factor 3 (IRF 3), IRF 7, and ISG 15. Viral copies rapidly increased at 12 hpi then remained high until 2 dpi. When viral copy numbers were high, a higher expression of immune genes IL 1β, IRF 3, IRF 7, Type I IFN, ISG 15 and Mx was observed. Viral copies were drastically reduced in 4 and 7 dpi fish, and also the immune response was considerably reduced but remained elevated, except for ISG 15 which found equal to control in 7 dpi fish. A high degree of correlation was observed between immune genes and viral copy number in each of the sampled fish at 12 hpi. A fish with ascites sampled at 7 dpi displayed high viral copy but under-expressed immune genes except for Mx. When viral copies were high at 1 and 2 dpi, both TLR 2 and TLR 7 were down-regulated, perhaps indicating immune suppression by the virus. The quick and prolonged elevated expression of the immune genes indicates their crucial role in survival of host against VHSV.

  11. Anopheles gambiae heat shock protein cognate 70B impedes o'nyong-nyong virus replication

    Directory of Open Access Journals (Sweden)

    Higgs Stephen

    2007-07-01

    Full Text Available Abstract Background Phylogenetic and functional analysis was conducted on an Anopheles gambiae gene, ENSANGG00000017398. Based on phylogenetic analysis, this gene belongs to the same lineage as Heat shock protein cognate 70-4 (Hsc70-4 in Drosophila. Accordingly, we propose to name this gene Heat shock protein cognate 70B (HSC70B. We previously reported that expression of HSC70B and other genes including elongation factor-1α (EF-1α and the agglutinin attachment subunit (agglutinin were up-regulated in o'nyong-nyong virus (ONNV-infected female An. gambiae. Double-stranded RNA interferences have been applied to further investigate HSC70B, EF-1α and the agglutinin functions in ONNV replication in An. gambiae. Results Among these three RNAi silenced genes, only dsRNAs of HSC70B (dsHSC70B promoted ONNV replication in adult An. gambiae compared to the control mosquitoes that were co-injected with ONNV and dsRNA of β-galactosidase (dsβ-gal. ONNV titers from mosquitoes co-injected with dsHSC70B were about 9-fold higher at 6 days post-injection (d.p.i. as compared to the control mosquitoes. By using ONNV tagged with enhanced green fluorescent protein (ONNV-eGFP, co-injection of ONNV-eGFP with dsHSC70B also showed approximately 2 ~ 3-fold higher GFP expression rates than the controls in the head, thorax, and abdomen of the mosquito. Furthermore, co-injection of ONNV with dsHSC70B significantly reduced the lifespan of adult mosquitoes as compared with the control, co-injection of ONNV with dsβ-gal treated mosquitoes. Conclusion These results indicate that HSC70B plays important roles in homeostasis and suppression of ONNV replication in the vector, An. gambiae. Biological implications of these findings are that while mosquitoes allow ONNV to replicate in them, they also check viral titers so that ONNV infection will result in no harmful effect on mosquitoes. Therefore, mosquitoes can function as vectors of ONNV transmission to humans while ONNV

  12. Homolog of allograft inflammatory factor-1 induces macrophage migration during innate immune response in leech.

    Science.gov (United States)

    Schorn, Tilo; Drago, Francesco; Tettamanti, Gianluca; Valvassori, Roberto; de Eguileor, Magda; Vizioli, Jacopo; Grimaldi, Annalisa

    2015-03-01

    Allograft inflammatory factor-1 (AIF-1) is a 17-kDa cytokine-inducible calcium-binding protein that, in vertebrates, plays an important role in the allograft immune response. Its expression is mostly limited to the monocyte/macrophage lineage. Until recently, AIF-1 was assumed to be a novel molecule involved in inflammatory responses. To clarify this aspect, we have investigated the expression of AIF-1 after bacterial challenge and its potential role in regulating the innate immune response in an invertebrate model, the medicinal leech (Hirudo medicinalis). Analysis of an expressed sequence tag library from the central nervous system of Hirudo revealed the presence of the gene Hmaif-1/alias Hmiba1, showing high homology with vertebrate aif-1. Immunohistochemistry with an anti-HmAIF-1 polyclonal antibody revealed the constitutive presence of this protein in spread CD68(+) macrophage-like cells. A few hours after pathogen (bacterial) injection into the body wall, the amount of these immunopositive cells co-expressing HmAIF-1 and the common leucocyte marker CD45 increased at the injected site. Moreover, the recombinant protein HmAIF-1 induced massive angiogenesis and was a potent chemoattractant for macrophages. Following rHmAIF-1 stimulation, macrophage-like cells co-expressed the macrophage marker CD68 and the surface glycoprotein CD45, which, in vertebrates, seems to have a role in the integrin-mediated adhesion of macrophages and in the regulation of the functional responsiveness of cells to chemoattractants. CD45 is therefore probably involved in leech macrophage-like cell activation and migration towards an inflammation site. We have also examined its potential effect on HmAIF-1-induced signalling.

  13. Transcription factor ICBP90 regulates the MIF promoter and immune susceptibility locus.

    Science.gov (United States)

    Yao, Jie; Leng, Lin; Sauler, Maor; Fu, Weiling; Zheng, Junsong; Zhang, Yi; Du, Xin; Yu, Xiaoqing; Lee, Patty; Bucala, Richard

    2016-02-01

    The immunoregulatory cytokine macrophage migration inhibitory factor (MIF) is encoded in a functionally polymorphic locus that is linked to the susceptibility of autoimmune and infectious diseases. The MIF promoter contains a 4-nucleotide microsatellite polymorphism (-794 CATT) that repeats 5 to 8 times in the locus, with greater numbers of repeats associated with higher mRNA levels. Because there is no information about the transcriptional regulation of these common alleles, we used oligonucleotide affinity chromatography and liquid chromatography-mass spectrometry to identify nuclear proteins that interact with the -794 CATT5-8 site. An analysis of monocyte nuclear lysates revealed that the transcription factor ICBP90 (also known as UHRF1) is the major protein interacting with the MIF microsatellite. We found that ICBP90 is essential for MIF transcription from monocytes/macrophages, B and T lymphocytes, and synovial fibroblasts, and TLR-induced MIF transcription is regulated in an ICBP90- and -794 CATT5-8 length-dependent manner. Whole-genome transcription analysis of ICBP90 shRNA-treated rheumatoid synoviocytes uncovered a subset of proinflammatory and immune response genes that overlapped with those regulated by MIF shRNA. In addition, the expression levels of ICBP90 and MIF were correlated in joint synovia from patients with rheumatoid arthritis. These findings identify ICBP90 as a key regulator of MIF transcription and provide functional insight into the regulation of the polymorphic MIF locus.

  14. Immune Reactions Against Elongation Factor 2 Kinase: Specific Pathogenesis of Gastric Ulcer from Helicobacter pylori Infection

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    Kiyoshi Ayada

    2009-01-01

    Full Text Available Helicobacter pylori (H. pylori infection is a definite causative factor for gastric ulcers (GUs. In the present study we detected a specific antigen of gastric epithelial cells (HGC-27 using cell ELISA, which was recognized by the sera of GU patients (n=20 but not in patients with chronic gastritis (CG; n=20 or in healthy volunteers (HC; n=10. This antigen was over-expressed by a stressful (heat-stressed environment, and was identified as elongation factor 2 kinase (EF-2K by western blotting. The GU patients' lymphocytes stimulated by H. pylori specifically disrupted heat-stressed HGC-27 cells in a cytotoxic assay. In flow cytometry, the effector cells (lymphocytes from GU patients were significantly differentiated to T helper type 1 lymphocyte (Th1 and cytotoxic T lymphocyte (CTL as opposed to those from CG patients. The target cells (HGC-27 expressed EF-2K and MHC-class I together with costimulatory molecules from heat stress. This antigen specific immune mechanism could have a prominent role in the pathogenesis of GU.

  15. Factors associated with complete immunization coverage in children aged 12–23 months in Ambo Woreda, Central Ethiopia

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    Etana Belachew

    2012-07-01

    Full Text Available Abstract Background Vaccination is a proven tool in preventing and eradicating communicable diseases, but a considerable proportion of childhood morbidity and mortality in Ethiopia is due to vaccine preventable diseases. Immunization coverage in many parts of the country remains low despite the efforts to improve the services. In 2005, only 20% of the children were fully vaccinated and about 1 million children were unvaccinated in 2007. The objective of this study was to assess complete immunization coverage and its associated factors among children aged 12–23 months in Ambo woreda. Methods A cross-sectional community-based study was conducted in 8 rural and 2 urban kebeles during January- February, 2011. A modified WHO EPI cluster sampling method was used for sample selection. Data on 536 children aged 12–23 months from 536 representative households were collected using trained nurses. The data collectors assessed the vaccination status of the children based on vaccination cards or mother’s verbal reports using a pre-tested structured questionnaire through house-to-house visits. Bivariate and multivariate logistic regression analyses were used to assess factors associated with immunization coverage. Results About 96% of the mothers heard about vaccination and vaccine preventable diseases and 79.5% knew the benefit of immunization. About 36% of children aged 12–23 months were fully vaccinated by card plus recall, but only 27.7% were fully vaccinated by card alone and 23.7% children were unvaccinated. Using multivariate logistic regression models, factors significantly associated with complete immunization were antenatal care follow-up (adjusted odds ratio(AOR = 2.4, 95% CI: 1.2- 4.9, being born in the health facility (AOR = 2.1, 95% CI: 1.3-3.4, mothers’ knowledge about the age at which vaccination begins (AOR = 2.9, 95% CI: 1.9-4.6 and knowledge about the age at which vaccination completes (AOR = 4.3, 95% CI: 2

  16. Aberrant interaction of the gut immune system with environmental factors in the development of food allergies.

    Science.gov (United States)

    Kunisawa, Jun; Kiyono, Hiroshi

    2010-05-01

    The gastrointestinal immune system is a major component of the mucosal barrier, which maintains an immunologic homeostasis between the host and the harsh environment of the gut. This homeostasis is achieved by immunologic quiescence, and its dysregulation is thought to result from the development of immune diseases such as food allergies. Recent findings have revealed versatile pathways in the development of intestinal allergies to certain food antigens. In this review, we summarize the regulatory and quiescence mechanisms in the gut immune system and describe aberrant interactions between the host immune system and the gut environment in the development of food allergies.

  17. Detergent-solubilized Patched purified from Sf9 cells fails to interact strongly with cognate Hedgehog or Ihog homologs.

    Science.gov (United States)

    Cleveland, Thomas E; McCabe, Jacqueline M; Leahy, Daniel J

    2014-12-01

    Patched (Ptc) is a twelve-pass transmembrane protein that functions as a receptor for the Hedgehog (Hh) family of morphogens. In addition to Ptc, several accessory proteins including the CDO/Ihog family of co-receptors are necessary for proper Hh signaling. Structures of Hh proteins bound to members of the CDO/Ihog family are known, but the nature of the full Hh receptor complex is not well understood. We have expressed the Drosophila Patched and Mouse Patched-1 proteins in Sf9 cells and find that Sonic Hedgehog will bind to Mouse Patched-1 in isolated Sf9 cell membranes but that purified, detergent-solubilized Ptc proteins do not interact strongly with cognate Hh and CDO/Ihog homologs. These results may reflect a nonnative conformation of detergent-solubilized Ptc or that an additional factor or factors lost during purification are required for high-affinity Ptc binding to Hh.

  18. A conserved peptide pattern from a widespread microbial virulence factor triggers pattern-induced immunity in Arabidopsis.

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    Hannah Böhm

    2014-11-01

    Full Text Available Microbe- or host damage-derived patterns mediate activation of pattern-triggered immunity (PTI in plants. Microbial virulence factor (effector-triggered immunity (ETI constitutes a second layer of plant protection against microbial attack. Various necrosis and ethylene-inducing peptide 1 (Nep1-like proteins (NLPs produced by bacterial, oomycete and fungal microbes are phytotoxic virulence factors that exert immunogenic activities through phytotoxin-induced host cell damage. We here show that multiple cytotoxic NLPs also carry a pattern of 20 amino acid residues (nlp20 that triggers immunity-associated plant defenses and immunity to microbial infection in Arabidopsis thaliana and related plant species with similar characteristics as the prototype pattern, bacterial flagellin. Characteristic differences in flagellin and nlp20 plant responses exist however, as nlp20s fail to trigger extracellular alkalinization in Arabidopsis cell suspensions and seedling growth inhibition. Immunogenic nlp20 peptide motifs are frequently found in bacterial, oomycete and fungal NLPs. Such an unusually broad taxonomic distribution within three phylogenetic kingdoms is unprecedented among microbe-derived triggers of immune responses in either metazoans or plants. Our findings suggest that cytotoxic NLPs carrying immunogenic nlp20 motifs trigger PTI in two ways as typical patterns and by inflicting host cell damage. We further propose that conserved structures within a microbial virulence factor might have driven the emergence of a plant pattern recognition system mediating PTI. As this is reminiscent of the evolution of immune receptors mediating ETI, our findings support the idea that there is a continuum between PTI and ETI.

  19. RELATIONSHIP OF CAROTID ARTERIES INTIMA-MEDIA THICKNESS WITH INFECTIOUS, IMMUNE, METABOLIC FACTORS AND INFLAMMATION MARKERS IN HEALTHY PERSONS

    Directory of Open Access Journals (Sweden)

    A. P. Shavrin

    2011-01-01

    Full Text Available Aim – to examine the relationship of arteries wall thickness with the indicators characterizing the infectious, immune, metabolic status inapparently healthy individuals.Materials and methods. The study included 342 patients (mean age 43.7 ± 0.5 years that in the process of cluster analysis on the thicknessof the intima-media thickness (IMT were divided into 3 groups. Group 1 consisted of patients with no risk factors of cardiovascular disease,2nd – patients with presence of these factors, 3rd – patients with atherosclerotic plaques in the carotid artery. All patients were examinedin complex: ultrasound of vessels measurement on the Aloka 5000 with IMT, evaluation of lipid profile, glucose level, determination of C-reactive protein (CRP in blood plasma and cytokines – tumor necrosis factor-α (TNF-α, interferon-γ (IFN-γ, interleukin (IL -1, -8, -4, specific antibody immunoglobulin G (IgG to cytomegalovirus (CMV, herpes simplex virus type 1 (HSV-1 , C. pneumoniae, H. pylori and β-hemolytic streptococci group A. Immune system status was assessed by innate and acquired immunity factors.Results. In groups of examined patients by increasing IMT of the common carotid artery infectious viruses (CMV, HSV-1 burden increased,what was obligatory for all groups. In the 3rd group, in 45 % of patients C. pneumoniae was found. In the 2nd and 3rd groups weakening ofacquired immunity was found out – reducing the total number of lymphocytes and T-lymphocytes, the increase of CRP and proinflammatory cytokines (IL-1, -8, IFN-γ, TNF-α, it was indicating development of inflammatory process, and in the third group it took characters of the system inflammatory response. In cluster analysis it was revealed that the process of thickening of the vascular wall is influenced by complex factors – infectious, metabolic and immune.Conclusion. The presence of the close relationship between the thickness of vessel walls and infectious, metabolic (lipid and

  20. RELATIONSHIP OF CAROTID ARTERIES INTIMA-MEDIA THICKNESS WITH INFECTIOUS, IMMUNE, METABOLIC FACTORS AND INFLAMMATION MARKERS IN HEALTHY PERSONS

    Directory of Open Access Journals (Sweden)

    A. P. Shavrin

    2014-07-01

    Full Text Available Aim – to examine the relationship of arteries wall thickness with the indicators characterizing the infectious, immune, metabolic status inapparently healthy individuals.Materials and methods. The study included 342 patients (mean age 43.7 ± 0.5 years that in the process of cluster analysis on the thicknessof the intima-media thickness (IMT were divided into 3 groups. Group 1 consisted of patients with no risk factors of cardiovascular disease,2nd – patients with presence of these factors, 3rd – patients with atherosclerotic plaques in the carotid artery. All patients were examinedin complex: ultrasound of vessels measurement on the Aloka 5000 with IMT, evaluation of lipid profile, glucose level, determination of C-reactive protein (CRP in blood plasma and cytokines – tumor necrosis factor-α (TNF-α, interferon-γ (IFN-γ, interleukin (IL -1, -8, -4, specific antibody immunoglobulin G (IgG to cytomegalovirus (CMV, herpes simplex virus type 1 (HSV-1 , C. pneumoniae, H. pylori and β-hemolytic streptococci group A. Immune system status was assessed by innate and acquired immunity factors.Results. In groups of examined patients by increasing IMT of the common carotid artery infectious viruses (CMV, HSV-1 burden increased,what was obligatory for all groups. In the 3rd group, in 45 % of patients C. pneumoniae was found. In the 2nd and 3rd groups weakening ofacquired immunity was found out – reducing the total number of lymphocytes and T-lymphocytes, the increase of CRP and proinflammatory cytokines (IL-1, -8, IFN-γ, TNF-α, it was indicating development of inflammatory process, and in the third group it took characters of the system inflammatory response. In cluster analysis it was revealed that the process of thickening of the vascular wall is influenced by complex factors – infectious, metabolic and immune.Conclusion. The presence of the close relationship between the thickness of vessel walls and infectious, metabolic (lipid and

  1. The effect of food limitation on immunity factors and disease resistance in the western tent caterpillar.

    Science.gov (United States)

    Myers, Judith H; Cory, Jenny S; Ericsson, Jerry D; Tseng, Michelle L

    2011-11-01

    Epizootics of nucleopolyhedrovirus characterize declines of cyclic populations of western tent caterpillars, Malacosoma pluviale californicum. In field populations, infection can be apparently lacking in one generation and high in the next. This may suggest an increase in the susceptibility to infection of larvae at peak density or the triggering of a vertically transmitted virus. Here, we test the hypothesis that reduced food availability, as may occur during population outbreaks of tent caterpillars, influences the immunocompetence of larvae and increases their susceptibility to viral infection. We compared immunity factors, hemolymph phenoloxidase and hemocyte numbers, and the susceptibility to nucleopolyhedroviral infection of fifth instar larvae that were fully or partially fed as fourth instars. To determine if maternal or transgenerational influences occurred, we also determined the susceptibility of the offspring of the treated parents to viral infection. Food limitation significantly reduced larval survival, development rate, larval and pupal mass, moth fecundity and levels of hemolymph phenoloxidase, but not the numbers of hemocytes. Neither the food-reduced larvae nor their offspring were more susceptible to viral infection and were possibly even less susceptible at intermediate viral doses. Food reduction did not activate latent or covert viral infection of larvae as might be expected as a response to stress. We conclude that reducing the food intake of fourth instar larvae to an extent that had measurable and realistic impacts on their life history characteristics was not translated into increased susceptibility to viral infection.

  2. TISSUE FACTOR EXPRESSION BY MYELOID CELLS CONTRIBUTES TO PROTECTIVE IMMUNE RESPONSE AGAINST Mycobacterium tuberculosis INFECTION

    Science.gov (United States)

    Venkatasubramanian, Sambasivan; Tripathi, Deepak; Tucker, Torry; Paidipally, Padmaja; Cheekatla, Satyanarayana; Welch, Elwyn; Raghunath, Anjana; Jeffers, Ann; Tvinnereim, Amy R.; Schechter, Melissa E; Andrade, Bruno B; Mackman, Nizel; Idell, Steven; Vankayalapati, Ramakrishna

    2015-01-01

    Tissue Factor (TF) is a transmembrane glycoprotein that plays an essential role in hemostasis by activating coagulation. TF is also expressed by monocytes/macrophages as part of the innate immune response to infections. In the current study, we determined the role of TF expressed by myeloid cells during Mycobacterium tuberculosis (M. tb) infection by using mice lacking the TF gene in myeloid cells (TFΔ) and human monocyte derived macrophages (MDMs). We found that during M. tb infection, a deficiency of TF in myeloid cells was associated with reduced inducible nitric oxide synthase (iNOS) expression, enhanced arginase 1 (Arg1) expression, enhanced IL-10 production and reduced apoptosis in infected macrophages, which augmented M. tb growth. Our results demonstrate that a deficiency of TF in myeloid cells promotes M2 like phenotype in M .tb infected macrophages. A deficiency in TF expression by myeloid cells was also associated with reduced fibrin deposition and increased matrix metalloproteases (MMP)-2 and MMP-9 mediated inflammation in M. tb infected lungs. Our studies demonstrate that TF expressed by myeloid cells has newly recognized abilities to polarize macrophages and to regulate M. tb growth. PMID:26471500

  3. Service volume and other factors affecting the costs of immunizations in the Gambia

    Science.gov (United States)

    Robertson, Robert L.; Davis, Joe H.; Jobe, Kebba

    1984-01-01

    The total cost of the Expanded Programme on Immunization and of its various components in the Gambia over a period of one year (from July 1980 to June 1981) was investigated, and the costs per immunization dose and per fully immunized child were calculated. The total costs were to a large extent (45%) due to the cost of personnel and fixed costs. Where there was efficient delivery of immunizations, the average cost per dose was about one-fifth of that in the most costly facilities (range: US$2.32 to $0.41). The lower costs were related to more intensive use of the facilities. The national average cost was $1.09. The implications of the results of this study for policies to reduce costs are discussed, and further areas of research are suggested that will provide improved information to guide decision-makers in the use of scarce immunization programme resources for better health in the world. PMID:6334570

  4. Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype

    DEFF Research Database (Denmark)

    da Silveira, W A; Palma, P V B; Sicchieri, R D

    2017-01-01

    from putative bCSC and reverse engineering of transcription control networks, we identified two networks associated with this phenotype. One controlled by SNAI2, TWIST1, BNC2, PRRX1 and TBX5 drives a mesenchymal or CSC-like phenotype. The second network is controlled by the SCML4, ZNF831, SP140...... and IKZF3 transcription factors which correspond to immune response modulators. Immune response network expression is correlated with pathological response to chemotherapy, and in the Basal subtype is related to better recurrence-free survival. In patient-derived xenografts, the expression...... of these networks in patient tumours is predictive of engraftment success. Our findings point out a potential molecular mechanism underlying the balance between immune surveillance and EMT activation in breast cancer. This molecular mechanism may be useful to the development of new target therapies....

  5. The mitochondrial fission factor dynamin-related protein 1 modulates T-cell receptor signalling at the immune synapse.

    Science.gov (United States)

    Baixauli, Francesc; Martín-Cófreces, Noa B; Morlino, Giulia; Carrasco, Yolanda R; Calabia-Linares, Carmen; Veiga, Esteban; Serrador, Juan M; Sánchez-Madrid, Francisco

    2011-04-06

    During antigen-specific T-cell activation, mitochondria mobilize towards the vicinity of the immune synapse. We show here that the mitochondrial fission factor dynamin-related protein 1 (Drp1) docks at mitochondria, regulating their positioning and activity near the actin-rich ring of the peripheral supramolecular activation cluster (pSMAC) of the immune synapse. Mitochondrial redistribution in response to T-cell receptor engagement was abolished by Drp1 silencing, expression of the phosphomimetic mutant Drp1S637D and the Drp1-specific inhibitor mdivi-1. Moreover, Drp1 knockdown enhanced mitochondrial depolarization and T-cell receptor signal strength, but decreased myosin phosphorylation, ATP production and T-cell receptor assembly at the central supramolecular activation cluster (cSMAC). Our results indicate that Drp1-dependent mitochondrial positioning and activity controls T-cell activation by fuelling central supramolecular activation cluster assembly at the immune synapse.

  6. DMPD: Lipopolysaccharide sensing an important factor in the innate immune response toGram-negative bacterial infections: benefits and hazards of LPShypersensitivity. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available portant factor in the innate immune response toGram-negative bacterial infections: benefits and hazards of L...une response toGram-negative bacterial infections: benefits and hazards of LPShyp...18406367 Lipopolysaccharide sensing an important factor in the innate immune response toGram-negative bacter...ial infections: benefits and hazards of LPShypersensitivity. Freudenberg MA, Tchapt

  7. The course of preexistent immune abnormalities in HIV-negative hemophiliacs treated for 2 years with a monoclonal purified factor-VIII concentrate

    NARCIS (Netherlands)

    Smid, W. M.; van der Meer, J.; Smit, J. W.; Halie, M. R.

    1993-01-01

    The administration of factor VIII concentrates has been associated with immune abnormalities in patients with severe haemophilia A, even in the absence of HIV infection. The effects of a monoclonal purified factor VIII concentrate, Hemofil M (Baxter), on preexistent immune abnormalities were

  8. Successful immune tolerance induction consisting of high-dose factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin: a case report

    Directory of Open Access Journals (Sweden)

    Kubisz Peter

    2012-10-01

    Full Text Available Abstract Introduction The development of factor VIII inhibitors is a serious complication of replacement therapy in patients with congenital hemophilia A. Immune tolerance induction has been accepted as the only clinically proven treatment allowing antigen-specific tolerance to factor VIII. However, some of its issues, such as patient selection, timing, factor VIII dosing, use of immunosuppressive or immunomodulatory procedures, still remain the subject of debate. Case presentation A case of a 3-year-old Caucasian boy with severe congenital hemophilia A, intron 22 inversion of the F8 gene and high-titer inhibitor, who underwent an immune tolerance induction according to the modified Bonn regimen (high doses of plasma-derived factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin is presented. The treatment lasted for 13 months and led to the eradication of inhibitor. Conclusion Addition of intravenous immunoglobulin did not negatively affect the course of immune tolerance induction and led to the rapid eradication of factor VIII inhibitor.

  9. PreImplantation factor (PIF*) regulates systemic immunity and targets protective regulatory and cytoskeleton proteins.

    Science.gov (United States)

    Barnea, Eytan R; Hayrabedyan, Soren; Todorova, Krassimira; Almogi-Hazan, Osnat; Or, Reuven; Guingab, Joy; McElhinney, James; Fernandez, Nelson; Barder, Timothy

    2016-07-01

    Secreted by viable embryos, PIF is expressed by the placenta and found in maternal circulation. It promotes implantation and trophoblast invasion, achieving systemic immune homeostasis. Synthetic PIF successfully transposes endogenous PIF features to non-pregnant immune and transplant models. PIF affects innate and activated PBMC cytokines and genes expression. We report that PIF targets similar proteins in CD14+, CD4+ and CD8+ cells instigating integrated immune regulation. PIF-affinity chromatography followed by mass-spectrometry, pathway and heatmap analysis reveals that SET-apoptosis inhibitor, vimentin, myosin-9 and calmodulin are pivotal for immune regulation. PIF acts on macrophages down-stream of LPS (lipopolysaccharide-bacterial antigen) CD14/TLR4/MD2 complex, targeting myosin-9, thymosin-α1 and 14-3-3eta. PIF mainly targets platelet aggregation in CD4+, and skeletal proteins in CD8+ cells. Pathway analysis demonstrates that PIF targets and regulates SET, tubulin, actin-b, and S100 genes expression. PIF targets systemic immunity and has a short circulating half-life. Collectively, PIF targets identified; protective, immune regulatory and cytoskeleton proteins reveal mechanisms involved in the observed efficacy against immune disorders. Copyright © 2016 Elsevier GmbH. All rights reserved.

  10. SIGIRR inhibits toll-like receptor 4, 5, 9-mediated immune responses in human airway epithelial cells.

    Science.gov (United States)

    Zhang, Chun; Wu, Xueling; Zhao, Yunfeng; Deng, Zhaoxia; Qian, Guisheng

    2011-01-01

    Human airway epithelial cells (HAEC) may contribute to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) through toll-like receptors (TLRs)-mediated molecular mechanisms. TLRs exist on the surface of HAEC where binding to their cognate ligands initiates airway inflammation. Single immunoglobulin interleukin-1 receptor-related protein (SIGIRR) is a member of the toll-interleukin-1 receptor (TIR) family that can negatively modulate the immune response. We carried out studies to characterize SIGIRR modulation of TLR-mediated immune response in HAEC and to define its mechanisms of action. Following treatment with various concentrations of LPS, flagellin and CpG DNA, the levels of cognate TLRs 4, 5, and 9 were measured in the supernatants of HAEC over-expressing the SIGIRR molecule. Moreover, the interaction of the TLR adaptor myeloid differentiation factor 88 (MyD88) with SIGIRR in response to LPS-, flagellin- and CpG DNA-stimulation was examined by co-immunoprecipitation. The findings from this study revealed that overexpression of SIGIRR in HAEC stimulated by LPS, flagellin or CpG DNA resulted in attenuated production of the inflammatory mediators IL-6 and TNF-α. This attenuation was not the result of decreased expression of TLR4, 5 or 9, but rather a sequestration of MyD88 to the TLRs. In conclusion, SIGIRR can inhibit TLR4, 5, and 9-mediated immune responses in HAEC and may be a valuable therapeutic target for the prevention of ALI/ARDS.

  11. Mycoplasma hyorhinis-Contaminated Cell Lines Activate Primary Innate Immune Cells via a Protease-Sensitive Factor.

    Science.gov (United States)

    Heidegger, Simon; Jarosch, Alexander; Schmickl, Martina; Endres, Stefan; Bourquin, Carole; Hotz, Christian

    2015-01-01

    Mycoplasma are a frequent and occult contaminant of cell cultures, whereby these prokaryotic organisms can modify many aspects of cell physiology, rendering experiments that are conducted with such contaminated cells problematic. Chronic Mycoplasma contamination in human monocytic cells lines has been associated with suppressed Toll-like receptor (TLR) function. In contrast, we show here that components derived from a Mycoplasma hyorhinis-infected cell line can activate innate immunity in non-infected primary immune cells. Release of pro-inflammatory cytokines such as IL-6 by dendritic cells in response to Mycoplasma hyorhinis-infected cell components was critically dependent on the adapter protein MyD88 but only partially on TLR2. Unlike canonical TLR2 signaling that is triggered in response to the detection of Mycoplasma infection, innate immune activation by components of Mycoplasma-infected cells was inhibited by chloroquine treatment and sensitive to protease treatment. We further show that in plasmacytoid dendritic cells, soluble factors from Mycoplasma hyorhinis-infected cells induce the production of large amounts of IFN-α. We conclude that Mycoplasma hyorhinis-infected cell lines release protein factors that can potently activate co-cultured innate immune cells via a previously unrecognized mechanism, thus limiting the validity of such co-culture experiments.

  12. The roles of host and pathogen factors and the innate immune response in the pathogenesis of Clostridium difficile infection

    Science.gov (United States)

    Sun, Xingmin; Hirota, Simon A.

    2014-01-01

    Clostridium difficile (C. difficile) is the most common cause of nosocomial antibiotic-associated diarrhea and the etiologic agent of pseudomembranous colitis. The clinical manifestation of Clostridium difficile infection (CDI) is highly variable, from asymptomatic carriage, to mild self-limiting diarrhea, to the more severe pseudomembranous colitis. Furthermore, in extreme cases, colonic inflammation and tissue damage can lead to toxic megacolon, a condition requiring surgical intervention. C. difficile expresses two key virulence factors; the exotoxins, toxin A (TcdA) and toxin B (TcdB), which are glucosyltransferases that target host-cell monomeric GTPases. In addition, some hypervirulent strains produce a third toxin, binary toxin or C. difficile transferase (CDT), which may contribute to the pathogenesis of CDI. More recently, other factors such as surface layer proteins (SLPs) and flagellin have also been linked to the inflammatory responses observed in CDI. Although the adaptive immune response can influence the severity of CDI, the innate immune responses to C. difficile and its toxins play crucial roles in CDI onset, progression, and overall prognosis. Despite this, the innate immune responses in CDI have drawn relatively little attention from clinical researchers. Targeting these responses may prove useful clinically as adjuvant therapies, especially in refractory and/or recurrent CDI. This review will focus on recent advances in our understanding of how C. difficile and its toxins modulate innate immune responses that contribute to CDI pathogenesis. PMID:25242213

  13. Accessory Factors of Cytoplasmic Viral RNA Sensors Required for Antiviral Innate Immune Response

    Science.gov (United States)

    Oshiumi, Hiroyuki; Kouwaki, Takahisa; Seya, Tsukasa

    2016-01-01

    Type I interferon (IFN) induces many antiviral factors in host cells. RIG-I-like receptors (RLRs) are cytoplasmic viral RNA sensors that trigger the signal to induce the innate immune response that includes type I IFN production. RIG-I and MDA5 are RLRs that form nucleoprotein filaments along viral double-stranded RNA, resulting in the activation of MAVS adaptor molecule. The MAVS protein forms a prion-like aggregation structure, leading to type I IFN production. RIG-I and MDA5 undergo post-translational modification. TRIM25 and Riplet ubiquitin ligases deliver a K63-linked polyubiquitin moiety to the RIG-I N-terminal caspase activation and recruitment domains (CARDs) and C-terminal region; the polyubiquitin chain then stabilizes the two-CARD tetramer structure required for MAVS assembly. MDA5 activation is regulated by phosphorylation. RIOK3 is a protein kinase that phosphorylates the MDA5 protein in a steady state, and PP1α/γ dephosphorylate this protein, resulting in its activation. RIG-I and MDA5 require cytoplasmic RNA helicases for their efficient activation. LGP2, another RLR, is an RNA helicase involved in RLR signaling. This protein does not possess N-terminal CARDs and, thus, cannot trigger downstream signaling by itself. Recent studies have revealed that this protein modulates MDA5 filament formation, resulting in enhanced type I IFN production. Several other cytoplasmic RNA helicases are involved in RLR signaling. DDX3, DHX29, DHX36, and DDX60 RNA helicases have been reported to be involved in RLR-mediated type I IFN production after viral infection. However, the underlying mechanism is largely unknown. Future studies are required to reveal the role of RNA helicases in the RLR signaling pathway. PMID:27252702

  14. Accessory Factors of Cytoplasmic Viral RNA Sensors Required for Antiviral Innate Immune Response.

    Science.gov (United States)

    Oshiumi, Hiroyuki; Kouwaki, Takahisa; Seya, Tsukasa

    2016-01-01

    Type I interferon (IFN) induces many antiviral factors in host cells. RIG-I-like receptors (RLRs) are cytoplasmic viral RNA sensors that trigger the signal to induce the innate immune response that includes type I IFN production. RIG-I and MDA5 are RLRs that form nucleoprotein filaments along viral double-stranded RNA, resulting in the activation of MAVS adaptor molecule. The MAVS protein forms a prion-like aggregation structure, leading to type I IFN production. RIG-I and MDA5 undergo post-translational modification. TRIM25 and Riplet ubiquitin ligases deliver a K63-linked polyubiquitin moiety to the RIG-I N-terminal caspase activation and recruitment domains (CARDs) and C-terminal region; the polyubiquitin chain then stabilizes the two-CARD tetramer structure required for MAVS assembly. MDA5 activation is regulated by phosphorylation. RIOK3 is a protein kinase that phosphorylates the MDA5 protein in a steady state, and PP1α/γ dephosphorylate this protein, resulting in its activation. RIG-I and MDA5 require cytoplasmic RNA helicases for their efficient activation. LGP2, another RLR, is an RNA helicase involved in RLR signaling. This protein does not possess N-terminal CARDs and, thus, cannot trigger downstream signaling by itself. Recent studies have revealed that this protein modulates MDA5 filament formation, resulting in enhanced type I IFN production. Several other cytoplasmic RNA helicases are involved in RLR signaling. DDX3, DHX29, DHX36, and DDX60 RNA helicases have been reported to be involved in RLR-mediated type I IFN production after viral infection. However, the underlying mechanism is largely unknown. Future studies are required to reveal the role of RNA helicases in the RLR signaling pathway.

  15. Accessory factors of cytoplasmic viral RNA sensors required for antiviral innate immune response

    Directory of Open Access Journals (Sweden)

    Hiroyuki eOshiumi

    2016-05-01

    Full Text Available Type I interferon (IFN induces many antiviral factors in host cells. RIG-I-like receptors (RLRs are cytoplasmic viral RNA sensors that trigger the signal to induce the innate immune response that includes type I IFN production. RIG-I and MDA5 are RLRs that form nucleoprotein filaments along viral double-stranded RNA, resulting in the activation of MAVS adaptor molecule. The MAVS protein forms a prion-like aggregation structure, leading to type I IFN production. RIG-I and MDA5 undergo post-translational modification. TRIM25 and Riplet ubiquitin ligases deliver a K63-linked polyubiquitin moiety to the RIG-I N-terminal caspase activation and recruitment domains (CARDs and C-terminal region; the polyubiquitin chain then stabilizes the two-CARD tetramer structure required for MAVS assembly. MDA5 activation is regulated by phosphorylation. RIOK3 is a protein kinase that phosphorylates the MDA5 protein in a steady state, and PP1α/γ dephosphorylate this protein, resulting in its activation. RIG-I and MDA5 require cytoplasmic RNA helicases for their efficient activation. LGP2, another RLR, is an RNA helicase involved in RLR signaling. This protein does not possess N-terminal CARDs and thus cannot trigger downstream signaling by itself. Recent studies have revealed that this protein modulates MDA5 filament formation, resulting in enhanced type I IFN production. Several other cytoplasmic RNA helicases are involved in RLR signaling. DDX3, DHX29, DHX36, and DDX60 RNA helicases have been reported to be involved in RLR-mediated type I IFN production after viral infection. However, the underlying mechanism is largely unknown. Future studies are required to reveal the role of RNA helicases in the RLR signaling pathway.

  16. Characterization and functional classification of American lobster (Homarus americanus) immune factor transcripts.

    Science.gov (United States)

    Clark, K Fraser

    2014-11-01

    The American lobster (Homarus americanus) is the most important commercially exploited marine species in Canada. Very little is known about the H. americanus molecular humoral immune response or how to determine if a seemingly healthy lobster is infected with a pathogen. The goal of this work is to characterize several important H. americanus immune genes as well as highlight and classify hundreds of others into functional immune groups. The protein sequence of H. americanus acute phase serum amyloid protein A (SAA) was found to be similar to that of vertebrate SAA, and is likely a good clinical marker for immune activation in lobsters and some crustaceans. Additionally, only one gene, Trypsin 1b, was found to be differentially regulated during bacterial, microparasitic and viral challenges in lobster and is likely critical for the activation of the H. americanus immune response. Bioinformatic analysis was used to functionally annotate, 263 H. americanus immune genes and identify the few shared patterns of differential gene expression in lobsters in response to bacterial, parasitic and viral challenge. Many of the described immune genes are biomarker candidates which could be used as clinical indicators for lobster health and disease. Biomarkers can facilitate early detection of pathogens, or anthropomorphic stressors, so that mitigation strategies can be developed in order to prevent the devastating economic losses that have occurred in Southern New England, USA. This work is contributes to further our understanding of how the lobster immune system works and how it can be used to maintain the health and sustainability of the overall American lobster fishery.

  17. Anti-CD3 antibodies modulate anti-factor VIII immune responses in hemophilia A mice after factor VIII plasmid-mediated gene therapy.

    Science.gov (United States)

    Peng, Baowei; Ye, Peiqing; Rawlings, David J; Ochs, Hans D; Miao, Carol H

    2009-11-12

    One major obstacle in gene therapy is the generation of immune responses directed against transgene product. Five consecutive anti-CD3 treatments concomitant with factor VIII (FVIII) plasmid injection prevented the formation of inhibitory antibodies against FVIII and achieved persistent, therapeutic levels of FVIII gene expression in treated hemophilia A mice. Repeated plasmid gene transfer is applicable in tolerized mice without eliciting immune responses. Anti-CD3 treatment significantly depleted both CD4+ and CD8+ T cells, whereas increased transforming growth factor-beta levels in plasma and the frequency of both CD4+CD25+FoxP3+ and CD4+CD25-Foxp3+ regulatory T cells in the initial few weeks after treatment. Although prior depletion of CD4+CD25+ cells did not abrogate tolerance induction, adoptive transfer of CD4+ cells from tolerized mice at 6 weeks after treatment protected recipient mice from anti-FVIII immune responses. Anti-CD3-treated mice mounted immune responses against both T-dependent and T-independent neo-antigens, indicating that anti-CD3 did not hamper the immune systems in the long term. Concomitant FVIII plasmid + anti-CD3 treatment induced long-term tolerance specific to FVIII via a mechanism involving the increase in transforming growth factor-beta levels and the generation of adaptive FVIII-specific CD4+Foxp3+ regulatory T cells at the periphery. Furthermore, anti-CD3 can reduce the titers of preexisting anti-FVIII inhibitory antibodies in hemophilia A mice.

  18. Levels of innate immune factors in preterm and term mothers' breast milk during the 1st month postpartum.

    Science.gov (United States)

    Trend, Stephanie; Strunk, Tobias; Lloyd, Megan L; Kok, Chooi Heen; Metcalfe, Jessica; Geddes, Donna T; Lai, Ching Tat; Richmond, Peter; Doherty, Dorota A; Simmer, Karen; Currie, Andrew

    2016-04-14

    There is a paucity of data on the effect of preterm birth on the immunological composition of breast milk throughout the different stages of lactation. We aimed to characterise the effects of preterm birth on the levels of immune factors in milk during the 1st month postpartum, to determine whether preterm milk is deficient in antimicrobial factors. Colostrum (days 2-5 postpartum), transitional milk (days 8-12) and mature milk (days 26-30) were collected from mothers of extremely preterm (preterm (28-preterm (32-preterm mothers had significantly higher concentrations of HBD1 and TGF-β2 in colostrum than term mothers did. After controlling for other variables in regression analyses, preterm birth was associated with higher concentrations of HBD1, LZ and sCD14 in milk samples. In conclusion, preterm breast milk contains significantly higher concentrations of some immune proteins than term breast milk.

  19. Serratia marcescens suppresses host cellular immunity via the production of an adhesion-inhibitory factor against immunosurveillance cells.

    Science.gov (United States)

    Ishii, Kenichi; Adachi, Tatsuo; Hamamoto, Hiroshi; Sekimizu, Kazuhisa

    2014-02-28

    Injection of a culture supernatant of Serratia marcescens into the bloodstream of the silkworm Bombyx mori increased the number of freely circulating immunosurveillance cells (hemocytes). Using a bioassay with live silkworms, serralysin metalloprotease was purified from the culture supernatant and identified as the factor responsible for this activity. Serralysin inhibited the in vitro attachment of both silkworm hemocytes and murine peritoneal macrophages. Incubation of silkworm hemocytes or murine macrophages with serralysin resulted in degradation of the cellular immune factor BmSPH-1 or calreticulin, respectively. Furthermore, serralysin suppressed in vitro phagocytosis of bacteria by hemocytes and in vivo bacterial clearance in silkworms. Disruption of the ser gene in S. marcescens attenuated its host killing ability in silkworms and mice. These findings suggest that serralysin metalloprotease secreted by S. marcescens suppresses cellular immunity by decreasing the adhesive properties of immunosurveillance cells, thereby contributing to bacterial pathogenesis.

  20. Predicting Growth in English and French Vocabulary: The Facilitating Effects of Morphological and Cognate Awareness

    Science.gov (United States)

    D'Angelo, Nadia; Hipfner-Boucher, Kathleen; Chen, Xi

    2017-01-01

    The present study investigated the contribution of morphological and cognate awareness to the development of English and French vocabulary knowledge among young minority and majority language children who were enrolled in a French immersion program. Participating children (n = 75) were assessed in English and French on measures of morphological…

  1. The Representation and Processing of Identical Cognates by Late Bilinguals: RT and ERP Effects

    Science.gov (United States)

    Peeters, David; Dijkstra, Ton; Grainger, Jonathan

    2013-01-01

    Across the languages of a bilingual, translation equivalents can have the same orthographic form and shared meaning (e.g., TABLE in French and English). How such words, called orthographically identical cognates, are processed and represented in the bilingual brain is not well understood. In the present study, late French-English bilinguals…

  2. L2 Vocabulary Acquisition in Children: Effects of Learning Method and Cognate Status

    Science.gov (United States)

    Tonzar, Claudio; Lotto, Lorella; Job, Remo

    2009-01-01

    In this study we investigated the effects of two learning methods (picture- or word-mediated learning) and of word status (cognates vs. noncognates) on the vocabulary acquisition of two foreign languages: English and German. We examined children from fourth and eighth grades in a school setting. After a learning phase during which L2 words were…

  3. Interlingual Influence in Bilingual Speech: Cognate Status Effect in a Continuum of Bilingualism

    Science.gov (United States)

    Amengual, Mark

    2012-01-01

    The present study investigates voice onset times (VOTs) to determine if cognates enhance the cross-language phonetic influences in the speech production of a range of Spanish-English bilinguals: Spanish heritage speakers, English heritage speakers, advanced L2 Spanish learners, and advanced L2 English learners. To answer this question, lexical…

  4. Spanish-English Cognates in the Subtechnical Vocabulary Found in Engineering Magazine Texts.

    Science.gov (United States)

    Martinez, Maria Stella

    1994-01-01

    The use of the cognate recognition strategy to enhance reading comprehension in a Latin American English-for-Special-Purposes context is considered. Focus is on the subtechnical vocabulary found in 40 texts from English engineering magazines, first describing vocabulary identification techniques and then assessing whether the items have Spanish…

  5. English-Spanish Cognates in the Charlotte Zolotow Award Picture Books: Vocabulary, Morphology, and Orthography Lessons for Latino ELLs

    Science.gov (United States)

    Montelongo, Jose A.; Hernandez, Anita C.; Herter, Roberta J.

    2016-01-01

    English-Spanish cognates are words that are orthographically and semantically identical or nearly identical in English and Spanish as a result of a common etymology. Because of the similarities in the two languages, Spanish-dominant Latino English Language Learners (ELLs) can be taught to recognize English cognates thereby increasing their…

  6. Dietary Supplementation of Astragalus Polysaccharides Enhanced Immune Components and Growth Factors EGF and IGF-1 in Sow Colostrum

    Science.gov (United States)

    Tan, Lunbo; Wei, Ting; Yuan, Anwen; He, Jun; Liu, Jinhui

    2017-01-01

    Colostrum is the main external resource providing piglets with nutrients and maternal immune molecules. Astragalus polysaccharides (APS) have been used as immunopotentiators in vitro and several animal models. This study aimed to determine the effects of APS on immune factors in sow colostrum and milk. The sow diet was supplemented with APS one week before the expected delivery date. Colostrum and milk were collected and designated as 0 h- (onset of parturition), 12 h-, and 24 h-colostrum and 36 h-milk postpartum. Samples were measured using porcine immunoglobulin (Ig) G, IgM, classical swine fever virus antibody (CSFV Ab), epidermal growth factor (EGF), and insulin-like growth factor- (IGF-) 1 ELISA Quantitation Kits. Dietary supplementation of APS significantly enhanced the presence of IgG, IgM, EGF, and IGF-1 in 0 h-colostrum (P < 0.001). The blocking rates of CSFV Ab were increased in samples from APS-supplemented sow when compared to those from the matched samples without APS treatment. The results indicate that supplement of APS could improve the immune components in sow colostrum and/or milk; and status of some specific vaccination could be determined through using colostrum or early milk in sow. PMID:28164139

  7. The Role of Platelet-Activating Factor in Chronic Inflammation, Immune Activation, and Comorbidities Associated with HIV Infection

    Science.gov (United States)

    Kelesidis, Theodoros; Papakonstantinou, Vasiliki; Detopoulou, Paraskevi; Fragopoulou, Elizabeth; Chini, Maria; Lazanas, Marios C.; Antonopoulou, Smaragdi

    2016-01-01

    With the advent of highly effective antiretroviral therapy, cardiovascular disease has become an important cause of morbidity and mortality among people with treated HIV-1, but the pathogenesis is unclear. Platelet-activating factor is a potent lipid mediator of inflammation that has immunomodulatory effects and a pivotal role in the pathogenesis of inflammatory disorders and cardiovascular disease. Limited scientific evidence suggests that the platelet-activating factor pathway may be a mechanistic link between HIV-1 infection, systemic inflammation, and immune activation that contribute to pathogenesis of chronic HIV-related comorbidities, including cardiovascular disease and HIV-associated neurocognitive disorders. In this review, we examine the mechanisms by which the cross-talk between HIV-1, immune dysregulation, inflammation, and perturbations in the platelet-activating factor pathway may directly affect HIV-1 immunopathogenesis. Understanding the role of platelet-activating factor in HIV-1 infection may pave the way for further studies to explore therapeutic interventions, such as diet, that can modify platelet-activating factor activity and use of platelet-activating factor inhibitors that might improve the prognosis of HIV-1 infected patients. PMID:26616844

  8. Transforming growth factor beta-activated kinase 1 (TAK1)-dependent checkpoint in the survival of dendritic cells promotes immune homeostasis and function

    OpenAIRE

    Wang, Yanyan; Huang, Gonghua; Vogel, Peter; Neale, Geoffrey; Reizis, Boris; Chi, Hongbo

    2012-01-01

    Homeostatic control of dendritic cell (DC) survival is crucial for adaptive immunity, but the molecular mechanism is not well defined. Moreover, how DCs influence immune homeostasis under steady state remains unclear. Combining DC-specific and -inducible deletion systems, we report that transforming growth factor beta-activated kinase 1 (TAK1) is an essential regulator of DC survival and immune system homeostasis and function. Deficiency of TAK1 in CD11c+ cells induced markedly elevated apopt...

  9. Risk factors for discordant immune response among HIV-infected patients initiating antiretroviral therapy: A retrospective cohort study

    Directory of Open Access Journals (Sweden)

    B P Muzah

    2012-11-01

    Full Text Available Background. The therapeutic goal of antiretroviral therapy (ART is sustained immune recovery and viral suppression. However, some patients experience poor CD4 cell count responses despite achieving viral suppression. Such discordant immune responses have been associated with poor clinical outcomes. Objective. We aimed to determine the prevalence of discordant immune response and explore associated factors in a retrospective cohort of patients attending 2 large public sector clinics, during the 6 months following ART initiation. Methods. Data were analysed from 810 HIV-infected adults initiated on first-line ART at 2 clinics in Johannesburg, between 1 November 2008 and 31 December 2009. Multivariate logistic regression models were used to estimate adjusted odds ratios (AORs to determine associations between discordant immune response and clinical and demographic factors. Results. At ART initiation, 65% (n=592 of participants were female, with a mean age of 38.5 years. Median baseline CD4 cell count was 155 cells/mm3, 70% (n=645 of patients had a haemoglobin level >11 g/dl and 88% (n=803 were initiated on stavudine-lamivudine-efavirenz/nevirapine (D4T-3TC-EFV/NVP. Six months after ART initiation, 24% (n=220 of patients had a discordant immune response and 7% (n=67 a discordant virological response. On multivariate analysis, baseline CD cell count ≥200 cells/mm3 (AOR 3.02; 95% confidence interval (CI 2.08 - 4.38; p<0.001 and moderate anaemia (8.0 - 9.4 g/dl at baseline (AOR 2.30; 95% CI 1.25 - 4.59; p=0.007 were independently associated with the development of discordant immune response, after adjustment for education level, World Health Organization (WHO clinical stage and ART regimen. Conclusions. Discordant immune response following ART initiation was common and associated with baseline anaemia and CD4 cell count in our cohort. Intensive monitoring of at-risk individuals may improve clinical outcomes.

  10. Phosphorylation of the conserved transcription factor ATF-7 by PMK-1 p38 MAPK regulates innate immunity in Caenorhabditis elegans.

    Science.gov (United States)

    Shivers, Robert P; Pagano, Daniel J; Kooistra, Tristan; Richardson, Claire E; Reddy, Kirthi C; Whitney, Janelle K; Kamanzi, Odile; Matsumoto, Kunihiro; Hisamoto, Naoki; Kim, Dennis H

    2010-04-01

    Innate immunity in Caenorhabditis elegans requires a conserved PMK-1 p38 mitogen-activated protein kinase (MAPK) pathway that regulates the basal and pathogen-induced expression of immune effectors. The mechanisms by which PMK-1 p38 MAPK regulates the transcriptional activation of the C. elegans immune response have not been identified. Furthermore, in mammalian systems the genetic analysis of physiological targets of p38 MAPK in immunity has been limited. Here, we show that C. elegans ATF-7, a member of the conserved cyclic AMP-responsive element binding (CREB)/activating transcription factor (ATF) family of basic-region leucine zipper (bZIP) transcription factors and an ortholog of mammalian ATF2/ATF7, has a pivotal role in the regulation of PMK-1-mediated innate immunity. Genetic analysis of loss-of-function alleles and a gain-of-function allele of atf-7, combined with expression analysis of PMK-1-regulated genes and biochemical characterization of the interaction between ATF-7 and PMK-1, suggest that ATF-7 functions as a repressor of PMK-1-regulated genes that undergoes a switch to an activator upon phosphorylation by PMK-1. Whereas loss-of-function mutations in atf-7 can restore basal expression of PMK-1-regulated genes observed in the pmk-1 null mutant, the induction of PMK-1-regulated genes by pathogenic Pseudomonas aeruginosa PA14 is abrogated. The switching modes of ATF-7 activity, from repressor to activator in response to activated PMK-1 p38 MAPK, are reminiscent of the mechanism of regulation mediated by the corresponding ancestral Sko1p and Hog1p proteins in the yeast response to osmotic stress. Our data point to the regulation of the ATF2/ATF7/CREB5 family of transcriptional regulators by p38 MAPK as an ancient conserved mechanism for the control of innate immunity in metazoans, and suggest that ATF2/ATF7 may function in a similar manner in the regulation of mammalian innate immunity.

  11. Phosphorylation of the conserved transcription factor ATF-7 by PMK-1 p38 MAPK regulates innate immunity in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Robert P Shivers

    2010-04-01

    Full Text Available Innate immunity in Caenorhabditis elegans requires a conserved PMK-1 p38 mitogen-activated protein kinase (MAPK pathway that regulates the basal and pathogen-induced expression of immune effectors. The mechanisms by which PMK-1 p38 MAPK regulates the transcriptional activation of the C. elegans immune response have not been identified. Furthermore, in mammalian systems the genetic analysis of physiological targets of p38 MAPK in immunity has been limited. Here, we show that C. elegans ATF-7, a member of the conserved cyclic AMP-responsive element binding (CREB/activating transcription factor (ATF family of basic-region leucine zipper (bZIP transcription factors and an ortholog of mammalian ATF2/ATF7, has a pivotal role in the regulation of PMK-1-mediated innate immunity. Genetic analysis of loss-of-function alleles and a gain-of-function allele of atf-7, combined with expression analysis of PMK-1-regulated genes and biochemical characterization of the interaction between ATF-7 and PMK-1, suggest that ATF-7 functions as a repressor of PMK-1-regulated genes that undergoes a switch to an activator upon phosphorylation by PMK-1. Whereas loss-of-function mutations in atf-7 can restore basal expression of PMK-1-regulated genes observed in the pmk-1 null mutant, the induction of PMK-1-regulated genes by pathogenic Pseudomonas aeruginosa PA14 is abrogated. The switching modes of ATF-7 activity, from repressor to activator in response to activated PMK-1 p38 MAPK, are reminiscent of the mechanism of regulation mediated by the corresponding ancestral Sko1p and Hog1p proteins in the yeast response to osmotic stress. Our data point to the regulation of the ATF2/ATF7/CREB5 family of transcriptional regulators by p38 MAPK as an ancient conserved mechanism for the control of innate immunity in metazoans, and suggest that ATF2/ATF7 may function in a similar manner in the regulation of mammalian innate immunity.

  12. Fas-associated factor 1 plays a negative regulatory role in the antibacterial immunity of Locusta migratoria.

    Science.gov (United States)

    He, Z; Wang, P; Shi, H; Si, F; Hao, Y; Chen, B

    2013-08-01

    Insect immune responses are precisely regulated to maintain immune balance. In this study, the Fas-associated factor 1 (FAF1) gene of Locusta migratoria manilensis, a homologue of the caspar gene that functions as a specific negative regulator in the antibacterial immunity pathway, was cloned. Gene expression analysis showed that FAF1 was expressed throughout the developmental stages and in all tested tissues, but its transcription levels varied significantly. Thus, FAF1 appears to be tightly regulated and is probably involved in multiple physiological processes. In addition, the antimicrobial peptide gene prolixicin was cloned and characterized. After bacterial challenge, prolixicin was rapidly up-regulated, whereas FAF1 was markedly down-regulated. This result was consistent with the observation that prolixicin was hyperactivated when FAF1 was suppressed by RNA interference. Moreover, after bacterial infection, the survival rate of FAF1-knockdown locusts was much higher than that of the wild-type. Taken together, these findings strongly suggest that FAF1 shares a similar function as caspar in Drosophila and may be involved in the negative regulation of antibacterial immunity in locusts.

  13. Cross-language activation of morphological relatives in cognates: The role of orthographic overlap and task-related processing

    Directory of Open Access Journals (Sweden)

    Kimberley eMulder

    2015-02-01

    Full Text Available We considered the role of orthography and task-related processing mechanisms in the activation of morphologically related complex words during bilingual word processing. So far, it has only been shown that such morphologically related words (i.e., morphological family members are activated through the semantic and morphological overlap they share with the target word. In this study, we investigated family size effects in Dutch-English identical cognates (e.g., tent in both languages, non-identical cognates (e.g., pil and pill, in English and Dutch, respectively, and non-cognates (e.g., chicken in English. Because of their cross-linguistic overlap in orthography, reading a cognate can result in activation of family members both languages. Cognates are therefore well-suited for studying mechanisms underlying bilingual activation of morphologically complex words. We investigated family size effects in an English lexical decision task and a Dutch-English language decision task, both performed by Dutch-English bilinguals. English lexical decision showed a facilitatory effect of English and Dutch family size on the processing of English-Dutch cognates relative to English non-cognates. These family size effects were not dependent on cognate type. In contrast, for language decision, in which a bilingual context is created, Dutch and English family size effects were inhibitory. Here, the combined family size of both languages turned out to better predict reaction time than the separate family size in Dutch or English. Moreover, the combined family size interacted with cognate type: The response to identical cognates was slowed by morphological family members in both languages. We conclude that (1 family size effects are sensitive to the task performed on the lexical items, and (2 depend on both semantic and formal aspects of bilingual word processing. We discuss various mechanisms that can explain the observed family size effects in a spreading

  14. Differential expression of migration inhibitory and migration stimulatory factors in two lines of mice genetically selected for high or low responsiveness to phytohemagglutinin. 1. Migration stimulatory factor(s) from T and B cells of immune spleen.

    Science.gov (United States)

    Gauthier-Rahman, S; el-Gharbi, N; Siddiqui, M U; Couderc, J; Decreusefond, C; Stiffel, C

    1991-01-01

    Expression of the lymphokine migration inhibition factor in two lines of mice genetically selected for the high (Hi/PHA) or low (Lo/PHA) response of their lymph node cells to phytohemagglutinin was found to be modulated by concomitant expression of migration stimulation factor(s) [MStF(s)]. The expression of both lymphokines was dependent on genetic character and the immunizing dose of antigen. In mice immunized 5 days earlier with 50 micrograms ovalbumin in Freund's complete adjuvant (Ova in FCA immune), migration inhibition factor, assessed with a sensitive photoelectric method, was well expressed by male spleen or lymph node 24-hour culture supernatants of Lo/PHA but Hi/PHA, especially female, expressed marked MStF(s) instead. Immunization with 500 micrograms Ova in FCA markedly enhanced expression of MStF(s) in Lo/PHA but inhibited it in Hi/PHA. MStF(s) of Ova in FCA immune spleens of the two lines were found to derive from both T and B cells, B cell activity being greater. Lo/PHA were by far better expressors of both T- and B-cell-derived MStF(s) as compared to Hi/PHA (p less than 0.01). Spleen cells of mice immunized with FCA alone also expressed MStF(s) but to lesser extent than Ova in FCA immune spleens, expression by Lo/PHA B cells being significantly higher than in Hi/PHA (p less than 0.05). The MStF(s) of Ova in FCA immune spleens was found to be non-immunoglobulin in nature.

  15. SAP expression in invariant NKT cells is required for cognate help to support B-cell responses.

    Science.gov (United States)

    Detre, Cynthia; Keszei, Marton; Garrido-Mesa, Natividad; Kis-Toth, Katalin; Castro, Wilson; Agyemang, Amma F; Veerapen, Natacha; Besra, Gurdyal S; Carroll, Michael C; Tsokos, George C; Wang, Ninghai; Leadbetter, Elizabeth A; Terhorst, Cox

    2012-07-05

    One of the manifestations of X-linked lymphoproliferative disease (XLP) is progressive agammaglobulinemia, caused by the absence of a functional signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) in T, invariant natural killer T (NKT) cells and NK cells. Here we report that α-galactosylceramide (αGalCer) activated NKT cells positively regulate antibody responses to haptenated protein antigens at multiple checkpoints, including germinal center formation and affinity maturation. Whereas NKT cell-dependent B cell responses were absent in SAP(-/-).B6 mice that completely lack NKT cells, the small number of SAP-deficient NKT cells in SAP(-/-).BALB/c mice adjuvated antibody production, but not the germinal center reaction. To test the hypothesis that SAP-deficient NKT cells can facilitate humoral immunity, SAP was deleted after development in SAP(fl/fl).tgCreERT2.B6 mice. We find that NKT cell intrinsic expression of SAP is dispensable for noncognate helper functions, but is critical for providing cognate help to antigen-specific B cells. These results demonstrate that SLAM-family receptor-regulated cell-cell interactions are not limited to T-B cell conjugates. We conclude that in the absence of SAP, several routes of NKT cell-mediated antibody production are still accessible. The latter suggests that residual NKT cells in XLP patients might contribute to variations in dysgammaglobulinemia.

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

    DEFF Research Database (Denmark)

    Baatrup, Gunnar; Petersen, Ivan; Kappelgaard, E;

    1984-01-01

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

  17. RAGE Expression in Human T Cells: A Link between Environmental Factors and Adaptive Immune Responses

    Science.gov (United States)

    Akirav, Eitan M.; Preston-Hurlburt, Paula; Garyu, Justin; Henegariu, Octavian; Clynes, Raphael; Schmidt, Ann Marie; Herold, Kevan C.

    2012-01-01

    The Receptor for Advanced Glycation Endproducts (RAGE) is a scavenger ligand that binds glycated endproducts as well as molecules released during cell death such as S100b and HMGB1. RAGE is expressed on antigen presenting cells where it may participate in activation of innate immune responses but its role in adaptive human immune responses has not been described. We have found that RAGE is expressed intracellularly in human T cells following TCR activation but constitutively on T cells from patients with diabetes. The levels of RAGE on T cells from patients with diabetes are not related to the level of glucose control. It co-localizes to the endosomes. Its expression increases in activated T cells from healthy control subjects but bystander cells also express RAGE after stimulation of the antigen specific T cells. RAGE ligands enhance RAGE expression. In patients with T1D, the level of RAGE expression decreases with T cell activation. RAGE+ T cells express higher levels of IL-17A, CD107a, and IL-5 than RAGE− cells from the same individual with T1D. Our studies have identified the expression of RAGE on adaptive immune cells and a role for this receptor and its ligands in modulating human immune responses. PMID:22509345

  18. Antigen-specific immune-suppressor factor in herpes simplex virus type 2 infections of UV B-irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Aurelian, L.; Yasumoto, S.; Smith, C.C.

    1988-07-01

    UV B-irradiation (280 to 320 nm) of mice at the site of cutaneous infection with herpes simplex virus type 2 (HSV-2) induced suppressor T-cell circuits that decreased HSV-2-induced proliferative responses of HSV-2-immune lymph node cells. Adoptive transfer experiments indicated that splenocytes from UV B-irradiated HSV-2-infected animals contain L3T4+ cells that suppress proliferative responses in vivo, consistent with suppressor inducer cells. However, following in vitro culture of the splenocytes with HSV-2 antigen, the proliferation of immune lymph node cells was inhibited by Lyt2+ suppressor T cells, consistent with antigen-induced suppressor effector cells. Antigen-specific and nonspecific suppressor factors were fractionated from supernatants of HSV-2-stimulated spleen cells by molecular-sieve chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the Sephadex fraction that contained the antigen-specific suppressor factor, in the presence or absence of 2-mercaptoethanol, defined a 115-kilodalton protein consisting of two disulfide-bound components with molecular sizes of 70 and 52 kilodaltons. The implications of these results with respect to the regulation of HSV-induced cell-mediated immunity following UV B-irradiation are discussed.

  19. Cloning changes the response to obesity of innate immune factors in blood, liver, and adipose tissues in domestic pigs.

    Science.gov (United States)

    Rødgaard, Tina; Skovgaard, Kerstin; Stagsted, Jan; Heegaard, Peter M H

    2013-06-01

    The objective of this study was to evaluate the usefulness of cloned pigs as porcine obesity models reflecting obesity-associated changes in innate immune factor gene expression profiles. Liver and adipose tissue expression of 43 innate immune genes as well as serum concentrations of six immune factors were analyzed in lean and diet-induced obese cloned domestic pigs and compared to normal domestic pigs (obese and lean). The number of genes affected by obesity was lower in cloned animals than in control animals. All genes affected by obesity in adipose tissues of clones were downregulated; both upregulation and downregulation were observed in the controls. Cloning resulted in a less differentiated adipose tissue expression pattern. Finally, the serum concentrations of two acute-phase proteins (APPs), haptoglobin (HP) and orosomucoid (ORM), were increased in obese clones as compared to obese controls as well as lean clones and controls. Generally, the variation in phenotype between individual pigs was not reduced in cloned siblings as compared to normal siblings. Therefore, we conclude that cloning limits both the number of genes responding to obesity as well as the degree of tissue-differentiated gene expression, concomitantly with an increase in APP serum concentrations only seen in cloned, obese pigs. This may suggest that the APP response seen in obese, cloned pigs is a consequence of the characteristic skewed gene response to obesity in cloned pigs, as described in this work. This should be taken into consideration when using cloned animals as models for innate responses to obesity.

  20. Brain-derived neurotrophic factor modulates immune reaction in mice with peripheral nerve xenotransplantation

    Directory of Open Access Journals (Sweden)

    Yu X

    2016-03-01

    mice than that in the spleen of XT only mice (P<0.05. Serum levels of IL-6, TNF-α, interferon-γ, and IL-17 were decreased, while IL-4 and IL-10 were stimulated by BDNF following xenotransplantation. Conclusion: BDNF reduced NK cells but increased NKT cell accumulation in the spleen of xenotransplanted mice. BDNF modulated the number of splenic T cells and its subtype cells in the mice following xenotransplantation. These findings suggest that BDNF inhibits rejection of peripheral nerve following xenotransplantation by regulating innate as well as adaptive immune reaction. Keywords: peripheral nerve, xenotransplantation, brain-derived neurotrophic factor

  1. Population differences in host immune factors may influence survival of Gunnison's prairie dogs (Cynomys Gunnisoni) during plague outbreaks

    Science.gov (United States)

    Busch, Joseph D.; Van Andel, Roger; Cordova, Jennifer; Colman, Rebecca E.; Keim, Paul; Rocke, Tonie E.; Leid, Jeff G.; Van Pelt, William E.; Wagner, David M.

    2011-01-01

    Over the past 40 yr, epizootics of plague (Yersinia pestis) in northern Arizona have reduced populations of the Gunnison’s prairie dog (Cynomys gunnisoni), with the exception of a large population found in the Aubrey Valley (AV). To examine potential mechanisms accounting for their survival, we collected prairie dog serum samples in 2005–2006 from AV and a neighboring population near Seligman (SE), Arizona. We quantified gene expression at 58 diverse immune proteins using a multiplexed enzyme-linked immunosorbent assay panel. We found a subset of proteins important in coagulation and inflammation (tissue factor [TF], calbindin [Cal], and thrombopoietin [TPO]) and T-cell responses (CD40L and CD40) that were present in AV at levels two to eight times greater than SE. These results suggest that AV and SE animals might differ in their ability to mount an immune response.

  2. The polyadenylation factor subunit CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR30: A key factor of programmed cell death and a regulator of immunity in arabidopsis

    KAUST Repository

    Bruggeman, Quentin

    2014-04-04

    Programmed cell death (PCD) is essential for several aspects of plant life, including development and stress responses. Indeed, incompatible plant-pathogen interactions are well known to induce the hypersensitive response, a localized cell death. Mutational analyses have identified several key PCD components, and we recently identified the mips1 mutant of Arabidopsis (Arabidopsis thaliana), which is deficient for the key enzyme catalyzing the limiting step of myoinositol synthesis. One of the most striking features of mips1 is the light-dependent formation of lesions on leaves due to salicylic acid (SA)-dependent PCD, revealing roles for myoinositol or inositol derivatives in the regulation of PCD. Here, we identified a regulator of plant PCD by screening for mutants that display transcriptomic profiles opposing that of the mips1 mutant. Our screen identified the oxt6 mutant, which has been described previously as being tolerant to oxidative stress. In the oxt6 mutant, a transfer DNA is inserted in the CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR30 (CPSF30) gene, which encodes a polyadenylation factor subunit homolog. We show that CPSF30 is required for lesion formation in mips1 via SA-dependent signaling, that the prodeath function of CPSF30 is not mediated by changes in the glutathione status, and that CPSF30 activity is required for Pseudomonas syringae resistance. We also show that the oxt6 mutation suppresses cell death in other lesion-mimic mutants, including lesion-simulating disease1, mitogen-activated protein kinase4, constitutive expressor of pathogenesis-related genes5, and catalase2, suggesting that CPSF30 and, thus, the control of messenger RNA 3′ end processing, through the regulation of SA production, is a key component of plant immune responses. © 2014 American Society of Plant Biologists. All rights reserved.

  3. Vascular endothelial growth factor receptor inhibitor SU5416 suppresses lymphocyte generation and immune responses in mice by increasing plasma corticosterone.

    Directory of Open Access Journals (Sweden)

    Jamison J Grailer

    Full Text Available Inhibitors of vascular endothelial growth factor and its receptors (VEGFRs are attractive therapeutic candidates for cancer treatment. One such small molecule VEGFR inhibitor, SU5416, limits angiogenesis in vivo and is widely used for investigating VEGFR signaling in tumor pathophysiology. Herein, we describe novel actions of SU5416 on the immune system. Treatment of mice with SU5416 for 3 days induced significant reductions in size and cellularity of peripheral lymph nodes. Interestingly, SU5416 did not affect initial lymphocyte localization to peripheral lymph nodes but did reduce lymphocyte accumulation during long-term migration assays. Treatment with SU5416 also induced severe loss of double-positive thymocytes resulting in thymic atrophy and a reduction in peripheral B cells. Furthermore, immune responses following immunization were reduced in mice treated with SU5416. Findings of thymic atrophy and reduced weight gain during SU5416 treatment suggested elevated corticosterone levels. Indeed, a significant 5-fold increase in serum corticosterone was found 4 hours after treatment with SU5416. Importantly, adrenalectomy negated the effects of SU5416 treatment on primary immune tissues, and partial reversal of SU5416-induced changes was observed following blockade of glucocorticoid receptors. SU5416 has been reported to inhibit the activation of latent transforming growth factor (TGF-β, a cytokine involved in the regulation of glucocorticoid release by the adrenal glands. Interestingly, treatment with a TGF-β receptor inhibitor, showed a similar phenotype as SU5416 treatment, including elevated serum corticosterone levels and thymic atrophy. Therefore, these results suggest that SU5416 induces glucocorticoid release directly from the adrenal glands, possibly by inhibition of TGF-β activation.

  4. Molecular cloning and expression of a heat-shock cognate 70 (hsc70) gene from swordtail fish (Xiphophorus helleri)

    Institute of Scientific and Technical Information of China (English)

    LI Ningqiu; FU Xiaozhe; HAN Jingang; SHI Cunbin; HUANG Zhibin; WU Shuqin

    2013-01-01

    Heat shock proteins are a family of molecular chaperones that are involved in many aspects of protein homeostasis.In the present study,a full-length cDNA,encoding the constitutively expressed 70-kDa heat shock cognate protein (Hsc70),was isolated from swordtail fish (Xiphophorus helleri) and designated as XheHsc70.The Xhehsc70 cDNA was 2 104 bp long with an open reading frame of 1 941 bp,and it encoded a protein of 646 amino acids with a theoretical molecular weight of 70.77 kDa and an isoelectric point of 5.04.The deduced amino acid sequence shared 94.1%-98.6% identities with the Hsc70s from a number of other fish species.Tissue distribution results show that the Xhehsc70 mRNA was expressed in brain,heart,head kidney,kidney,spleen,liver,muscle,gill,and peripheral blood.After immunization with formalin-killed Vibrio alginolyticus cells there was a significant increase in the Xhehsc70 rnRNA transcriptional level in the head kidney of the vaccinated fish compared with in the control at 6,12,24,and 48 h as shown by quantitative real time RT-PCR.Based on an analysis of the amino acid sequence of XheHsc70,its phylogeny,and Xhehsc70 mRNA expression,XheHsc70 was identified as a member of the cytoplasmic Hsc70 (constitutive) subfamily of the Hsp70 family of heat shock proteins,suggesting that it may play a role in the immune response.The Xhehsc70 cDNA sequence reported in this study was submitted to GenBank under the accession number JF739182.

  5. Molecular cloning and expression of a heat-shock cognate 70 (hsc70) gene from swordtail fish ( Xiphophorus helleri)

    Science.gov (United States)

    Li, Ningqiu; Fu, Xiaozhe; Han, Jingang; Shi, Cunbin; Huang, Zhibin; Wu, Shuqin

    2013-07-01

    Heat shock proteins are a family of molecular chaperones that are involved in many aspects of protein homeostasis. In the present study, a full-length cDNA, encoding the constitutively expressed 70-kDa heat shock cognate protein (Hsc70), was isolated from swordtail fish ( Xiphophorus helleri) and designated as XheHsc70. The Xhehsc70 cDNA was 2 104 bp long with an open reading frame of 1 941 bp, and it encoded a protein of 646 amino acids with a theoretical molecular weight of 70.77 kDa and an isoelectric point of 5.04. The deduced amino acid sequence shared 94.1%-98.6% identities with the Hsc70s from a number of other fish species. Tissue distribution results show that the Xhehsc70 mRNA was expressed in brain, heart, head kidney, kidney, spleen, liver, muscle, gill, and peripheral blood. After immunization with formalin-killed Vibrio alginolyticus cells there was a significant increase in the Xhehsc70 mRNA transcriptional level in the head kidney of the vaccinated fish compared with in the control at 6, 12, 24, and 48 h as shown by quantitative real time RT-PCR. Based on an analysis of the amino acid sequence of XheHsc70, its phylogeny, and Xhehsc70 mRNA expression, XheHsc70 was identified as a member of the cytoplasmic Hsc70 (constitutive) subfamily of the Hsp70 family of heat shock proteins, suggesting that it may play a role in the immune response. The Xhehsc70 cDNA sequence reported in this study was submitted to GenBank under the accession number JF739182.

  6. Human pathogenic Borrelia spielmanii sp. nov. resists complement-mediated killing by direct binding of immune regulators factor H and factor H-like protein 1.

    Science.gov (United States)

    Herzberger, Pia; Siegel, Corinna; Skerka, Christine; Fingerle, Volker; Schulte-Spechtel, Ulrike; van Dam, Alje; Wilske, Bettina; Brade, Volker; Zipfel, Peter F; Wallich, Reinhard; Kraiczy, Peter

    2007-10-01

    Borrelia spielmanii sp. nov. has recently been shown to be a novel human pathogenic genospecies that causes Lyme disease in Europe. In order to elucidate the immune evasion mechanisms of B. spielmanii, we compared the abilities of isolates obtained from Lyme disease patients and tick isolate PC-Eq17 to escape from complement-mediated bacteriolysis. Using a growth inhibition assay, we show that four B. spielmanii isolates, including PC-Eq17, are serum resistant, whereas a single isolate, PMew, was more sensitive to complement-mediated lysis. All isolates activated complement in vitro, as demonstrated by covalent attachment of C3 fragments; however, deposition of the later activation products C6 and C5b-9 was restricted to the moderately serum-resistant isolate PMew and the serum-sensitive B. garinii isolate G1. Furthermore, serum adsorption experiments revealed that all B. spielmanii isolates acquired the host alternative pathway regulators factor H and factor H-like protein (FHL-1) from human serum. Both complement regulators retained their factor I-mediated C3b inactivation activities when bound to spirochetes. In addition, two distinct factor H and FHL-1 binding proteins, BsCRASP-1 and BsCRASP-2, were identified, which we estimated to be approximately 23 to 25 kDa in mass. A further factor H binding protein, BsCRASP-3, was found exclusively in the tick isolate, PC-Eq17. This is the first report describing an immune evasion mechanism utilized by B. spielmanii sp. nov., and it demonstrates the capture of human immune regulators to resist complement-mediated killing.

  7. Lexical and semantic representations in the acquisition of L2 cognate and non-cognate words: evidence from two learning methods in children.

    Science.gov (United States)

    Comesaña, Montserrat; Soares, Ana Paula; Sánchez-Casas, Rosa; Lima, Cátia

    2012-08-01

    How bilinguals represent words in two languages and which mechanisms are responsible for second language acquisition are important questions in the bilingual and vocabulary acquisition literature. This study aims to analyse the effect of two learning methods (picture- vs. word-based method) and two types of words (cognates and non-cognates) in early stages of children's L2 acquisition. Forty-eight native speakers of European Portuguese, all sixth graders (mean age = 10.87 years; SD= 0.85), participated in the study. None of them had prior knowledge of Basque (the L2 in this study). After a learning phase in which L2 words were learned either by a picture- or a word-based method, children were tested in a backward-word translation recognition task at two times (immediately vs. one week later). Results showed that the participants made more errors when rejecting semantically related than semantically unrelated words as correct translations (semantic interference effect). The magnitude of this effect was higher in the delayed test condition regardless of the learning method. Moreover, the overall performance of participants from the word-based method was better than the performance of participants from the picture-word method. Results were discussed concerning the most significant bilingual lexical processing models.

  8. English-Spanish Cognates and the Pura Belpré Children's Award Books: Reading the Word and the World

    Science.gov (United States)

    Montelongo, José A.; Hernández, Anita C.; Herter, Roberta J.

    2014-01-01

    English-Spanish cognates are an important subset of words in both the English and Spanish languages. Cognates are words that possess identical or nearly identical spellings and meanings in both languages as a result of being derived from Latin and Greek. Of major importance is the fact that many of the more than 20,000 cognates in English are…

  9. The Role of NF-κB Factor REL2 in the Aedes aegypti Immune Response

    OpenAIRE

    Antonova, Yevgeniya; Alvarez, Kanwal S.; Kim, Yu Jung; Kokoza, Vladimir; Raikhel, Alexander S.

    2009-01-01

    Mosquitoes transmit numerous diseases that continue to be an enormous burden on public health worldwide. Transgenic mosquitoes impervious to vector-borne pathogens, in concert with vector control and drug and vaccine development, comprise an arsenal of means anticipated to defeat mosquito-spread diseases in the future. Mosquito transgenesis allows tissue-specific manipulation of their major immune pathways and enhances the ability to study mosquito–pathogen interactions. Here, we report the g...

  10. The Role of NF-κB Factor REL2 in the Aedes aegypti Immune Response

    OpenAIRE

    Antonova, Yevgeniya; Alvarez, Kanwal S.; Kim, Yu Jung; Kokoza, Vladimir; Raikhel, Alexander S.

    2009-01-01

    Mosquitoes transmit numerous diseases that continue to be an enormous burden on public health worldwide. Transgenic mosquitoes impervious to vector-borne pathogens, in concert with vector control and drug and vaccine development, comprise an arsenal of means anticipated to defeat mosquito-spread diseases in the future. Mosquito transgenesis allows tissue-specific manipulation of their major immune pathways and enhances the ability to study mosquito–pathogen interactions. Here, we report the g...

  11. A photophysical study of two fluorogen-activating proteins bound to their cognate fluorogens

    Energy Technology Data Exchange (ETDEWEB)

    Gaiotto, Tiziano [Los Alamos National Laboratory; Nguyen, Hau B [Los Alamos National Laboratory; Jung, Jaemyeong [Los Alamos National Laboratory; Bradbury, Andrew M [Los Alamos National Laboratory; Gnanakaran, S. [Los Alamos National Laboratory; Schmidt, Jurgen G [Los Alamos National Laboratory; Waldo, Geoffrey S [Los Alamos National Laboratory; Goodwin, Peter M [Los Alamos National Laboratory

    2010-12-14

    We are exploring the feasibility of using recently developed flu orogen-activating proteins (FAPs) as reporters for single-molecule imaging. FAPs are single-chain antibodies choosen to specifically bind small chromophoric molecules termed f1uorogens. Upon binding to its cognate FAP the fluorescence quantum yield of the fluorogen can increase substantially giving rise to a fluorescent complex. Based on the seminal work of Szent-Gyorgyi et al. (Nature Biotechnology, Volume 26, Number 2, pp 235-240, 2008) we have chosen to study two fluorogen-activating single-chain antibodies, HL 1.0.1-TOI and H6-MG bound to their cognate fluorogens, thiazole orange and malachite green derivatives, respectively. Here we use fluorescence correlation spectroscopy study the photophysics of these fluorescent complexes.

  12. Asteroid Pond Mineralogy: View from a Cognate Clast in LL3 NWA 8330

    Science.gov (United States)

    Zolensky, M.; Le, L.

    2017-01-01

    All asteroids surfaces imaged at the cm-scale reveal the presence of pond deposits. These ponds are important because it is likely all asteroid sample return missions will sample them, being the safest (very flat) places to touch down. Therefore, it is essential to understand the differences between the material at the pond surfaces and the host asteroid. Fortunately, some fine-grained cognate lithologies in chondrites show sedimentary features indicating that they sample asteroid ponds.

  13. Migration inhibitory factor (MIF) released by macrophages upon recognition of immune complexes is critical to inflammation in Arthus reaction.

    Science.gov (United States)

    Paiva, Claudia N; Arras, Rosa H; Magalhães, Elisabeth S; Alves, Letícia S; Lessa, Luiz Paulo; Silva, Maria Helena; Ejzemberg, Regina; Canetti, Cláudio; Bozza, Marcelo T

    2009-05-01

    Deposition of immune complexes (IC) triggers Fc gamma R-dependent inflammation, leading to tissue damage in rheumatoid arthritis, systemic lupus erythematous, immune glomerulonephritis, and several immune vasculitides. Evidences support a role for macrophage migration inhibitory factor (MIF) in a number of inflammatory diseases, but the triggering of its secretion and its physiopathological role upon IC deposition remain elusive. Herein, we show that human macrophages secreted MIF after IC recognition, which in turn controlled the secretion of TNF. Macrophages from Mif-/- mice produced smaller amounts of TNF when stimulated with IgG-opsonized erythrocytes than wild-type (WT) cells. Using passive reverse Arthus reaction in the peritoneum and lungs as a model for IC-induced inflammation, we demonstrated that Mif-/- mice had a milder response, observed by reduced neutrophil recruitment, vascular leakage, and secretion of TNF, MIP-2, and keratinocyte-derived chemokine compared with WT controls. Adoptive transfer of alveolar macrophages from WT to Mif-/- mice rescued pulmonary neutrophil recruitment and TNF production upon passive reverse Arthus reaction. Our study indicates that Arthus inflammatory reaction is largely dependent on MIF and poses macrophages as a source of the MIF released upon IC recognition. These results give experimental support to the proposition that blockade of MIF might constitute an adjunctive, therapeutic approach to IC disease.

  14. The onset of adaptive immunity in the mouse model of tuberculosis and the factors that compromise its expression.

    Science.gov (United States)

    Robinson, Richard T; Orme, Ian M; Cooper, Andrea M

    2015-03-01

    Mycobacterium tuberculosis (Mtb) has been evolving with its human host for over 50 000 years and is an exquisite manipulator of the human immune response. It induces both a strong inflammatory and a strong acquired immune response, and Mtb then actively regulates these responses to create an infectious lesion in the lung while maintaining a relatively ambulatory host. The CD4(+) T cell plays a critical yet contradictory role in this process by both controlling disseminated disease while promoting the development of the lesion in the lung that mediates transmission. In light of this manipulative relationship between Mtb and the human immune response, it is not surprising that our ability to vaccinate against tuberculosis (TB) has not been totally successful. To overcome the current impasse in vaccine development, we need to define the phenotype of CD4(+) T cells that mediate protection and to determine those bacterial and host factors that regulate the effective function of these cells. In this review, we describe the initiation and expression of T cells during TB as well as the fulminant inflammatory response that can compromise T-cell function and survival.

  15. A pair of light signaling factors FHY3 and FAR1 regulates plant immunity by modulating chlorophyll biosynthesis.

    Science.gov (United States)

    Wang, Wanqing; Tang, Weijiang; Ma, Tingting; Niu, De; Jin, Jing Bo; Wang, Haiyang; Lin, Rongcheng

    2016-01-01

    Light and chloroplast function is known to affect the plant immune response; however, the underlying mechanism remains elusive. We previously demonstrated that two light signaling factors, FAR-RED ELONGATED HYPOCOTYL 3 (FHY3) and FAR-RED IMPAIRED RESPONSE 1 (FAR1), regulate chlorophyll biosynthesis and seedling growth via controlling HEMB1 expression in Arabidopsis thaliana. In this study, we reveal that FHY3 and FAR1 are involved in modulating plant immunity. We showed that the fhy3 far1 double null mutant displayed high levels of reactive oxygen species and salicylic acid (SA) and increased resistance to Pseudomonas syringae pathogen infection. Microarray analysis revealed that a large proportion of pathogen-related genes, particularly genes encoding nucleotide-binding and leucine-rich repeat domain resistant proteins, are highly induced in fhy3 far1. Genetic studies indicated that the defects of fhy3 far1 can be largely rescued by reducing SA signaling or blocking SA accumulation, and by overexpression of HEMB1, which encodes a 5-aminolevulinic acid dehydratase in the chlorophyll biosynthetic pathway. Furthermore, we found that transgenic plants with reduced expression of HEMB1 exhibit a phenotype similar to fhy3 far1. Taken together, this study demonstrates an important role of FHY3 and FAR1 in regulating plant immunity, through integrating chlorophyll biosynthesis and the SA signaling pathway.

  16. The innate immune response transcription factor relish is necessary for neurodegeneration in a Drosophila model of ataxia-telangiectasia.

    Science.gov (United States)

    Petersen, Andrew J; Katzenberger, Rebeccah J; Wassarman, David A

    2013-05-01

    Neurodegeneration is a hallmark of the human disease ataxia-telangiectasia (A-T) that is caused by mutation of the A-T mutated (ATM) gene. We have analyzed Drosophila melanogaster ATM mutants to determine the molecular mechanisms underlying neurodegeneration in A-T. Previously, we found that ATM mutants upregulate the expression of innate immune response (IIR) genes and undergo neurodegeneration in the central nervous system. Here, we present evidence that activation of the IIR is a cause of neurodegeneration in ATM mutants. Three lines of evidence indicate that ATM mutations cause neurodegeneration by activating the Nuclear Factor-κB (NF-κB) transcription factor Relish, a key regulator of the Immune deficiency (Imd) IIR signaling pathway. First, the level of upregulation of IIR genes, including Relish target genes, was directly correlated with the level of neurodegeneration in ATM mutants. Second, Relish mutations inhibited upregulation of IIR genes and neurodegeneration in ATM mutants. Third, overexpression of constitutively active Relish in glial cells activated the IIR and caused neurodegeneration. In contrast, we found that Imd and Dif mutations did not affect neurodegeneration in ATM mutants. Imd encodes an activator of Relish in the response to gram-negative bacteria, and Dif encodes an immune responsive NF-κB transcription factor in the Toll signaling pathway. These data indicate that the signal that causes neurodegeneration in ATM mutants activates a specific NF-κB protein and does so through an unknown activator. In summary, these findings suggest that neurodegeneration in human A-T is caused by activation of a specific NF-κB protein in glial cells.

  17. Dietary Supplementation of Astragalus Polysaccharides Enhanced Immune Components and Growth Factors EGF and IGF-1 in Sow Colostrum.

    Science.gov (United States)

    Tan, Lunbo; Wei, Ting; Yuan, Anwen; He, Jun; Liu, Jinhui; Xu, Daojun; Yang, Qing

    2017-01-01

    Colostrum is the main external resource providing piglets with nutrients and maternal immune molecules. Astragalus polysaccharides (APS) have been used as immunopotentiators in vitro and several animal models. This study aimed to determine the effects of APS on immune factors in sow colostrum and milk. The sow diet was supplemented with APS one week before the expected delivery date. Colostrum and milk were collected and designated as 0 h- (onset of parturition), 12 h-, and 24 h-colostrum and 36 h-milk postpartum. Samples were measured using porcine immunoglobulin (Ig) G, IgM, classical swine fever virus antibody (CSFV Ab), epidermal growth factor (EGF), and insulin-like growth factor- (IGF-) 1 ELISA Quantitation Kits. Dietary supplementation of APS significantly enhanced the presence of IgG, IgM, EGF, and IGF-1 in 0 h-colostrum (P colostrum and/or milk; and status of some specific vaccination could be determined through using colostrum or early milk in sow.

  18. Risk factors and immunity in a nationally representative population following the 2009 influenza A(H1N1 pandemic.

    Directory of Open Access Journals (Sweden)

    Don Bandaranayake

    Full Text Available BACKGROUND: Understanding immunity, incidence and risk factors of the 2009 influenza A(H1N1 pandemic (2009 H1N1 through a national seroprevalence study is necessary for informing public health interventions and disease modelling. METHODS AND FINDINGS: We collected 1687 serum samples and individual risk factor data between November-2009 to March-2010, three months after the end of the 2009 H1N1 wave in New Zealand. Participants were randomly sampled from selected general practices countrywide and hospitals in the Auckland region. Baseline immunity was measured from 521 sera collected during 2004 to April-2009. Haemagglutination inhibition (HI antibody titres of ≥1:40 against 2009 H1N1 were considered seroprotective as well as seropositive. The overall community seroprevalence was 26.7% (CI:22.6-29.4. The seroprevalence varied across age and ethnicity. Children aged 5-19 years had the highest seroprevalence (46.7%;CI:38.3-55.0, a significant increase from the baseline (14%;CI:7.2-20.8. Older adults aged ≥60 had no significant difference in seroprevalence between the serosurvey (24.8%;CI:18.7-30.9 and baseline (22.6%;CI:15.3-30.0. Pacific peoples had the highest seroprevalence (49.5%;CI:35.1-64.0. There was no significant difference in seroprevalence between both primary (29.6%;CI:22.6-36.5 and secondary healthcare workers (25.3%;CI:20.8-29.8 and community participants. No significant regional variation was observed. Multivariate analysis indicated age as the most important risk factor followed by ethnicity. Previous seasonal influenza vaccination was associated with higher HI titres. Approximately 45.2% of seropositive individuals reported no symptoms. CONCLUSIONS: Based on age and ethnicity standardisation to the New Zealand Population, about 29.5% of New Zealanders had antibody titers at a level consistent with immunity to 2009 H1N1. Around 18.3% of New Zealanders were infected with the virus during the first wave including about one child

  19. Barrier to Autointegration Factor (BANF1): interwoven roles in nuclear structure, genome integrity, innate immunity, stress responses and progeria.

    Science.gov (United States)

    Jamin, Augusta; Wiebe, Matthew S

    2015-06-01

    The Barrier to Autointegration Factor (BAF or BANF1) is an abundant, highly conserved DNA binding protein. BAF is involved in multiple pathways including mitosis, nuclear assembly, viral infection, chromatin and gene regulation and the DNA damage response. BAF is also essential for early development in metazoans and relevant to human physiology; BANF1 mutations cause a progeroid syndrome, placing BAF within the laminopathy disease spectrum. This review summarizes previous knowledge about BAF in the context of recent discoveries about its protein partners, posttranslational regulation, dynamic subcellular localizations and roles in disease, innate immunity, transposable elements and genome integrity.

  20. Genomic analysis of host - Peste des petits ruminants vaccine viral transcriptome uncovers transcription factors modulating immune regulatory pathways.

    Science.gov (United States)

    Manjunath, Siddappa; Kumar, Gandham Ravi; Mishra, Bishnu Prasad; Mishra, Bina; Sahoo, Aditya Prasad; Joshi, Chaitanya G; Tiwari, Ashok K; Rajak, Kaushal Kishore; Janga, Sarath Chandra

    2015-02-24

    Peste des petits ruminants (PPR), is an acute transboundary viral disease of economic importance, affecting goats and sheep. Mass vaccination programs around the world resulted in the decline of PPR outbreaks. Sungri 96 is a live attenuated vaccine, widely used in Northern India against PPR. This vaccine virus, isolated from goat works efficiently both in sheep and goat. Global gene expression changes under PPR vaccine virus infection are not yet well defined. Therefore, in this study we investigated the host-vaccine virus interactions by infecting the peripheral blood mononuclear cells isolated from goat with PPRV (Sungri 96 vaccine virus), to quantify the global changes in the transcriptomic signature by RNA-sequencing. Viral genome of Sungri 96 vaccine virus was assembled from the PPRV infected transcriptome confirming the infection and demonstrating the feasibility of building a complete non-host genome from the blood transcriptome. Comparison of infected transcriptome with control transcriptome revealed 985 differentially expressed genes. Functional analysis showed enrichment of immune regulatory pathways under PPRV infection. Key genes involved in immune system regulation, spliceosomal and apoptotic pathways were identified to be dysregulated. Network analysis revealed that the protein - protein interaction network among differentially expressed genes is significantly disrupted in infected state. Several genes encoding TFs that govern immune regulatory pathways were identified to co-regulate the differentially expressed genes. These data provide insights into the host - PPRV vaccine virus interactome for the first time. Our findings suggested dysregulation of immune regulatory pathways and genes encoding Transcription Factors (TFs) that govern these pathways in response to viral infection.

  1. [Justifying genetic and immune markers of efficiency and sensitivity under combined exposure to risk factors in mining industry workers].

    Science.gov (United States)

    Dolgikh, O V; Zaitseva, N V; Krivtsov, A V; Gorshkova, K G; Lanin, D V; Bubnova, O A; Dianova, D G; Lykhina, T S; Vdovina, N A

    2014-01-01

    The authors evaluated and justified immunologic and genetic markers under combined exposure to risk factors in mining industry workers. Analysis covered polymorphism features of 29 genes with variant alleles possibly participating in occupationally conditioned diseases formation and serving as sensitivity markers of these diseases risk. The genes association selected demonstrates reliably changed polymorphism vs. the reference group (SOD2 superoxidedismutase gene, ANKK1 dophamine receptor gene, SULT1A1 sulphtransaminase gene, MTHFR methylene tetrahydrofolate reductase gene, VEGF endothelial growth factor gene, TNF-alpha tumor necrosis factor gene). Under combined exposure to occupational hazards (sylvinite dust, noise) in mining industry, this association can serve as adequate marking complex of sensitivity to development of occupationally conditioned diseases. Increased-production of immune cytokine regulation markers: tumor necrosis factor and vascular endothelial growth factor. Genes SOD2, ANKK1, SULT1A1, VEGF, TNFalpha are recommended as sensitivity markers, and the coded cytokines (tumor necrosis factor and endothelial growth factor) are proposed as effect markers in evaluation of health risk for workers in mining industry.

  2. Gene Expression and Localization of NGF and Its Cognate Receptors NTRK1 and NGFR in the Sex Organs of Male Rabbits.

    Science.gov (United States)

    Maranesi, M; Zerani, M; Leonardi, L; Pistilli, A; Arruda-Alencar, J; Stabile, A M; Rende, M; Castellini, C; Petrucci, L; Parillo, F; Moura, A; Boiti, C

    2015-12-01

    Experiments were devised to characterize the expression of nerve growth factor, beta polypeptide (NGF), and its cognate receptors neurotrophic tyrosine kinase receptor type 1 (NTRK1) and nerve growth factor receptor (NGFR) in rabbit male sex organs, as well as the concentrations of NGF in both seminal and blood plasma of sexually mature male rabbits. Immunoreactivity and gene expression for NGF and cognate receptors were detected in testis, prostate gland and seminal vesicle. The highest levels of NGF and NTRK1 transcripts were found in the prostate, while intermediate expressions were found in the testis. NGFR transcripts were expressed at the same levels in both testis and prostate and were more abundant than in seminal vesicles. The widespread distribution of NGF in all prostate glandular cells, together with its relative high mRNA abundance, confirms that the prostate of rabbits is the main source of this neurotrophin. In conclusion, the present data suggest that the NGF system is involved in the testicular development and spermatogenesis of rabbits and that NGF may act as a potential ovulation-inducing factor being abundantly present in the seminal plasma.

  3. Geometrical Configuration of Cabling as Factor Influencing the Reproducibility of EMC Immunity Tests

    Directory of Open Access Journals (Sweden)

    I. Szolik

    2006-12-01

    Full Text Available The paper deals with analysis of the influence of geometrical configuration of device cabling upon voltages induced in cable interfaces. The analyzed properties are the cable height and the cable length for common mode disturbance, and the loop width for differential mode disturbance. The analysis is solved both by analytical calculation and by numerical simulation. Achieved results are compared mutually as well as with results obtained by measurements performed according to standardized procedures. Finally the analyzed parameters are ordered in correspondence of their importance for objectivity and reproducibility of immunity tests against electromagnetic field.

  4. Factors of Suppression of Immune Response in Patients with Pulmonary Tuberculosis and Eosinophilia.

    Science.gov (United States)

    Urazova, O I; Novitskii, V V; Kolobovnikova, Yu V; Churina, E G

    2015-07-01

    We studied possible mechanisms of immunosuppression mediated by regulatory T cells that promotes suppression of antigen-specific immune response to Mycobacterium tuberculosis in patients with pulmonary tuberculosis and eosinophilia. It was shown that the number of CD4(+)CD25(+)Foxp3(+) regulatory T cells with immunosuppressive activity (Treg) increased in the peripheral blood of patients with disseminated destructive forms of pulmonary tuberculosis with multiple resistance of the causative agent to antituberculosis substances and eosinophilia. These changes were accompanied by imbalance in secretion of Treg-associated cytokines (in vitro) manifested in hyperproduction of TGFβ and IL-10 and decreased production of IL-2.

  5. Immune regulatory gene polymorphisms as predisposing risk factors for the development of factor VIII inhibitors in Indian severe haemophilia A patients.

    Science.gov (United States)

    Pinto, P; Ghosh, K; Shetty, S

    2012-09-01

    Development of inhibitors to factor VIII, a serious complication of replacement therapy in haemophilia A patients, leads to increased bleeding, morbidity and mortality. There is no data on the risk factors for inhibitor development in Indian patients with severe haemophilia A. Our aim was to study the role of immune regulatory gene polymorphisms in the development of inhibitors. Fourteen immune regulatory gene polymorphisms (IL1β, IL4, IL10, TNFA and CTLA4) were analysed in 120 patients with severe haemophilia A, i.e. 50 inhibitor positive patients, and 70 inhibitor negative control patients, by PCR-RFLP, DNA sequencing and allele-specific PCRs. The IL10 promoter 'GCC' haplotypes overall (P: 0.002, OR: 3.452, 95% CI: 1.607-7.416), and 'GCC/ATA' (P: 0.011, OR: 3.492, 95% CI: 1.402-8.696) haplotype, associated with high and intermediate IL10 production, respectively, were significantly higher in inhibitor positive patients, whereas the 'non-GCC' haplotypes overall (P: 0.002,OR: 0.290, 95% CI 0.135-0.622) and 'ATA/ATA' haplotype (P: 0.025, OR: 0.278, 95% CI: 0.096-0.802), associated with low IL10 synthesis, were significantly higher among inhibitor negative patients. The TNFA rs1799724 C/T heterozygote prevalence was significantly higher in the inhibitor positive group (P: 0.021, OR: 3.190, 95% CI: 1.273-7.990), whereas the other polymorphisms showed no statistically significant association with the presence of inhibitors. Different immune regulatory gene polymorphisms play a significant role as possible risk factors for the development of inhibitors in severe haemophilia A patients. © 2012 Blackwell Publishing Ltd.

  6. The Nuclear Factor kappaB Pathway: A Link to the Immune System in the Radiation Response

    Science.gov (United States)

    Hellweg, Christine; Baumstark-Khan, Christa; Reitz, Guenther; Chishti, Arif Ali; Koch, Kristina; Manchanda, Kashish

    Understanding the cellular radiation response is an essential prerequisite for the risk assessment of astronauts’ space radiation exposure during long-term space missions and for effective countermeasure development. In addition to the space radiation effects, other environmental factors during space missions such as microgravity have profound effects on the body, e.g. suppression of the innate and acquired immune response. Exposure to ionizing radiation modulates immune responses in a complex dose-dependent pattern, with possible anti-inflammatory effects in the low dose range, expression of pro-inflammatory cytokines at moderate doses and immunosuppression after exposure to higher doses due to precursor cell death together with concomitant exacerbated innate immune responses. A central regulator in the immune system is the transcription factor Nuclear Factor kB (NF-kappaB). In this work, the role of NF-kappaB in the cellular response to space relevant radiation qualities was analyzed. It was shown with a recombinant human NF-kappaB reporter cell line that heavy ions with a linear energy transfer (LET) of 100-300 keV/µm have a nine times higher potential to activate the NF-kappaB pathway compared to X-rays (150 kV). ATM was essential for NF-kappaB activation in response to X-rays and heavy ions. Knockdown of the NF-kappaB subunit RelA (p65) resulted in higher sensitivity towards X-rays. Reverse Transcriptase real-time quantitative PCR (RT-qPCR) experiments showed that after exposure to radiation, NF-kappaB predominantly upregulates genes involved in intercellular communication processes, especially genes coding for chemokines, suggesting an important contribution of NF-kappaB in the molecular profile of the reaction to radiation, which can comprise features of inflammation and wound healing processes. This is process is strictly NF-kappaB dependent as this response is completely absent in RelA knockdown cells. These results show that the role of NF-kappaB in

  7. First prospective report on immune tolerance in poor risk haemophilia A inhibitor patients with a single factor VIII/von Willebrand factor concentrate in an observational immune tolerance induction study.

    Science.gov (United States)

    Kreuz, W; Escuriola Ettingshausen, C; Vdovin, V; Zozulya, N; Plyushch, O; Svirin, P; Andreeva, T; Bubanská, E; Campos, M; Benedik-Dolničar, M; Jiménez-Yuste, V; Kitanovski, L; Klukowska, A; Momot, A; Osmulskaya, N; Prieto, M; Šalek, S Z; Velasco, F; Pavlova, A; Oldenburg, J; Knaub, S; Jansen, M; Belyanskaya, L; Walter, O

    2016-01-01

    Development of neutralizing inhibitors against factor VIII (FVIII) is a major complication of haemophilia A treatment. The ongoing, international, open-label, uncontrolled, observational immune tolerance induction (ObsITI) study evaluates ITI, the standard of care in patients with inhibitors. Forty-eight prospective patients in this interim analysis received a single plasma-derived, von Willebrand factor-stabilized, FVIII concentrate (pdFVIII/VWF) for ITI. According to recommended Bonn protocol, 'low responders' at ITI start (2 years since inhibitor diagnosis, inhibitor titre ≥10 BU at the start of ITI, or prior ITI failure). Nonetheless, 34 patients (70.8%) achieved complete success, 3 (6.3%) partial success, 1 (2.1%) partial response; ITI failed in 10 patients (20.8%), all with poor prognosis factors. All six low responders achieved complete success. ITI outcome was significantly associated with inhibitor titre level at ITI start (P = 0.0068), number of poor prognosis factors for ITI success (P = 0.0187), monthly bleeding rate during ITI (P = 0.0005) and peak inhibitor titre during ITI (P = 0.0007). Twenty-two of 35 high responder patients (62.9%) with ≥1 poor prognosis factor achieved complete success. Treatment with a single pdFVIII/VWF concentrate, mainly according to the Bonn protocol, resulted in a high ITI success rate in haemophilia A patients with inhibitors and poor prognosis for ITI success. © 2015 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

  8. Alternative splicing in the fiddler crab cognate ecdysteroid receptor: variation in receptor isoform expression and DNA binding properties in response to hormone.

    Science.gov (United States)

    Durica, David S; Das, Sunetra; Najar, Fares; Roe, Bruce; Phillips, Barret; Kappalli, Sudha; Anilkumar, Gopinathan

    2014-09-15

    RXR cDNA cloning from three Uca species led to the identification of 4 conserved isoforms, indicative of alternative splicing in the hinge and ligand binding domains (LBD). Sequencing of overlapping clones from a Ucapugilator genomic library identified EcR isoforms matching previously identified cDNA variants; in addition, a cryptic exon in the LBD was detected and evidence for expression of this new isoform was obtained from next-generation sequencing. RNA-seq analysis also identified a new amino terminal EcR variant. EcR and RXR transcript abundance increases throughout ovarian maturation in U. pugilator, while cognate receptor transcript abundance remains constant in a related Indo-Pacific species with a different reproductive strategy. To examine if crab RXR LBD isoforms have different physical properties in vitro, electromobility shift assays were performed with different EcR isoforms. The cognate crab and fruit fly receptors differ in their responses to hormone. Ecdysteroids did not increase DNA binding for the crab heterodimers, while ecdysteroids stimulate binding for Drosophilamelanogaster EcR/USP heterodimers. In swapping experiments, UpEcR/USP heterodimers did not show ligand-responsive differences in DNA binding; both crab RXR LBD isoforms, however, conferred ligand-responsive increases in DNA binding with DmEcRs. These data indicate that both UpRXR LBD isoforms can heterodimerize with the heterologous DmEcR receptors and promote ligand and DNA binding. Unresponsiveness of the cognate receptors to ecdysteroid, however, suggest additional factors may be required to mediate endogenous, perhaps isoform-specific, differences in EcR conformation, consistent with previously reported effects of UpRXR isoforms on UpEcR ligand-binding affinities.

  9. Cancer Stem Cell-Secreted Macrophage Migration Inhibitory Factor Stimulates Myeloid Derived Suppressor Cell Function and Facilitates Glioblastoma Immune Evasion

    DEFF Research Database (Denmark)

    Otvos, Balint; Silver, Daniel J; Mulkearns-Hubert, Erin E

    2016-01-01

    Shifting the balance away from tumor-mediated immune suppression toward tumor immune rejection is the conceptual foundation for a variety of immunotherapy efforts currently being tested. These efforts largely focus on activating antitumor immune responses but are confounded by multiple immune cel...

  10. Exogenous heat shock cognate protein 70 pretreatment attenuates cardiac and hepatic dysfunction with associated anti-inflammatory responses in experimental septic shock.

    Science.gov (United States)

    Hsu, Jong-Hau; Yang, Rei-Cheng; Lin, Shih-Jen; Liou, Shu-Fen; Dai, Zen-Kong; Yeh, Jwu-Lai; Wu, Jiunn-Ren

    2014-12-01

    It has been recently demonstrated that intracellular heat shock cognate protein 70 (HSC70) can be released into extracellular space with physiologic effects. However, its extracellular function in sepsis is not clear. In this study, we hypothesize that extracellular HSC70 can protect against lipopolysaccharide (LPS)-induced myocardial and hepatic dysfunction because of its anti-inflammatory actions. In Wistar rats, septic shock developed with hypotension, tachycardia, and myocardial and hepatic dysfunction at 4 h following LPS administration (10 mg/kg, i.v.). Pretreatment with recombinant bovine HSC70 (20 μg/kg, i.v.) attenuated LPS-induced hypotension and tachycardia by 21% and 23%, respectively (P shock cognate protein 70 also prevented LPS-induced hypoglycemia (217 vs. 59 mg/dL, P shock, extracellular HSC70 conveys pleiotropic protection on myocardial, hepatic, and systemic derangements, with associated inhibition of proinflammatory mediators including tumor necrosis factor α, nitric oxide, cyclooxygenase 2, and matrix metalloproteinase 9, through mitogen-activated protein kinase/nuclear factor κB signaling pathways. Therefore, extracellular HSC70 may have a promising role in the prophylactic treatment of sepsis.

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

    Science.gov (United States)

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

    2015-12-01

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

  12. Ataluren stimulates ribosomal selection of near-cognate tRNAs to promote nonsense suppression.

    Science.gov (United States)

    Roy, Bijoyita; Friesen, Westley J; Tomizawa, Yuki; Leszyk, John D; Zhuo, Jin; Johnson, Briana; Dakka, Jumana; Trotta, Christopher R; Xue, Xiaojiao; Mutyam, Venkateshwar; Keeling, Kim M; Mobley, James A; Rowe, Steven M; Bedwell, David M; Welch, Ellen M; Jacobson, Allan

    2016-11-01

    A premature termination codon (PTC) in the ORF of an mRNA generally leads to production of a truncated polypeptide, accelerated degradation of the mRNA, and depression of overall mRNA expression. Accordingly, nonsense mutations cause some of the most severe forms of inherited disorders. The small-molecule drug ataluren promotes therapeutic nonsense suppression and has been thought to mediate the insertion of near-cognate tRNAs at PTCs. However, direct evidence for this activity has been lacking. Here, we expressed multiple nonsense mutation reporters in human cells and yeast and identified the amino acids inserted when a PTC occupies the ribosomal A site in control, ataluren-treated, and aminoglycoside-treated cells. We find that ataluren's likely target is the ribosome and that it produces full-length protein by promoting insertion of near-cognate tRNAs at the site of the nonsense codon without apparent effects on transcription, mRNA processing, mRNA stability, or protein stability. The resulting readthrough proteins retain function and contain amino acid replacements similar to those derived from endogenous readthrough, namely Gln, Lys, or Tyr at UAA or UAG PTCs and Trp, Arg, or Cys at UGA PTCs. These insertion biases arise primarily from mRNA:tRNA mispairing at codon positions 1 and 3 and reflect, in part, the preferred use of certain nonstandard base pairs, e.g., U-G. Ataluren's retention of similar specificity of near-cognate tRNA insertion as occurs endogenously has important implications for its general use in therapeutic nonsense suppression.

  13. Cholesterol Accumulation in CD11c(+) Immune Cells Is a Causal and Targetable Factor in Autoimmune Disease.

    Science.gov (United States)

    Ito, Ayaka; Hong, Cynthia; Oka, Kazuhiro; Salazar, Jon V; Diehl, Cody; Witztum, Joseph L; Diaz, Mercedes; Castrillo, Antonio; Bensinger, Steven J; Chan, Lawrence; Tontonoz, Peter

    2016-12-20

    Liver X receptors (LXRs) are regulators of cholesterol metabolism that also modulate immune responses. Inactivation of LXR α and β in mice leads to autoimmunity; however, how the regulation of cholesterol metabolism contributes to autoimmunity is unclear. Here we found that cholesterol loading of CD11c(+) cells triggered the development of autoimmunity, whereas preventing excess lipid accumulation by promoting cholesterol efflux was therapeutic. LXRβ-deficient mice crossed to the hyperlipidemic ApoE-deficient background or challenged with a high-cholesterol diet developed autoantibodies. Cholesterol accumulation in lymphoid organs promoted T cell priming and stimulated the production of the B cell growth factors Baff and April. Conversely, B cell expansion and the development of autoantibodies in ApoE/LXR-β-deficient mice was reversed by ApoA-I expression. These findings implicate cholesterol imbalance as a contributor to immune dysfunction and suggest that stimulating HDL-dependent reverse cholesterol transport could be beneficial in the setting of autoimmune disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Enhancement of innate immune system in monocot rice by transferring the dicotyledonous elongation factor Tu receptor EFR

    Institute of Scientific and Technical Information of China (English)

    Fen Lu; Huiqin Wang; Shanzhi Wang; Wendi Jiang; Changlin Shan; Bin Li; Jun Yang; Shiyong Zhang; Wenxian Sun

    2015-01-01

    The elongation factor Tu (EF-Tu) receptor (EFR) in cruciferous plants specifical y recognizes the N-terminal acetylated elf18 region of bacterial EF-Tu and thereby activates plant immunity. It has been demonstrated that Arabidopsis EFR confers broad-spectrum bacterial resistance in the EFR transgenic solanaceous plants. Here, the transgenic rice plants (Oryza sativa L. ssp. japonica cv. Zhonghua 17) and cel cultures with constitutive expression of AtEFR were developed to investigate whether AtEFR senses EF-Tu and thus enhances bacterial resistance in the monocot plants. We demonstrated that the Xanthomonas oryzae-derived elf18 peptide induced oxidative burst and mitogen-activated protein kinase activa-tion in the AtEFR transgenic rice cel s and plants, respectively. Pathogenesis-related genes, such as OsPBZ1, were upregulated dramatical y in transgenic rice plant and cel lines in response to elf18 stimulation. Importantly, pretreatment with elf18 trig-gered strong resistance to X. oryzae pv. oryzae in the transgenic plants, which was largely dependent on the AtEFR expression level. These plants also exhibited enhanced resistance to rice bacterial brown stripe, but not to rice fungal blast. Col ectively, the results indicate that the rice plants with heterologous expression of AtEFR recognize bacterial EF-Tu and exhibit enhanced broad-spectrum bacterial disease resistance and that pattern recognition receptor-mediated immunity may be manipulated across the two plant classes, dicots and monocots.

  15. Transforming Growth Factor Beta-Based Therapies, a Potential Modulator of the Immune Response in Type 1 Diabetes?

    Directory of Open Access Journals (Sweden)

    E. Allison Green

    2015-11-01

    Full Text Available Immunobiological interventions are proving to be an exciting new area for mobilising the immune response towards certain tumours. In contrast, classical immunotherapeutic interventions aimed at dampening the autoimmune response to host tissue have been less successful; this is particularly evident for Type 1 diabetes (T1D. In part, the failure to control autoimmunity in T1D relates to the complexity of the immune response to β cells. To resolve this dilemma, immunologists are turning to immunobiological agents that were initially deemed too high risk for therapeutic use due to their potential to inadvertently promote autoimmunity or induce deleterious side effects. Two of these immunobiological mediators under consideration are transforming growth factor β (TGFβ and tolerogenic dendritic cells (DCs, both of which have shown robust control of the anti-islet response in animal models of T1D, the latter also recently documented to be acceptable for trialling in patients with T1D. In this review, both the challenges of translating immunobiological therapies discovered in animal models of T1D to man and the potential of TGFβ and tolerogenic DCs in the T1D setting will be discussed.

  16. Porcine models for the study of local and systemic regulation of innate immune factors in obesity

    DEFF Research Database (Denmark)

    Højbøge, Tina Rødgaard

    the number of animals to be used in a trial to obtain statistical power. For the gene regulation analysis, two platforms for quantitative real-time PCR (qPCR) were employed: The Rotor-Gene Q instrument and the microfluidics-based high-throughput Bio-Mark. For the serum protein concentrations analysis several...... enzyme-linked immunosorbent assays (ELISAs) were used on the blood. In the clones, both cloning and obesity changed the response of the innate immune genes in the tissues and in the blood, as fewer genes were differentially regulated in the clones and in the obese, than in the controls and lean pigs...... in gene expression in the tissues as nine genes in the liver (out of 35), 12 genes in the VAT, 11 in the RPAT and eight genes in the neck SAT (out of 33) were significantly differentially regulated in the obese Göttingen minipigs compared to lean. Three genes were differentially expressed in all three...

  17. TCTP is a critical factor in shrimp immune response to virus infection.

    Directory of Open Access Journals (Sweden)

    Wenlin Wu

    Full Text Available The translationally controlled tumor protein (TCTP is an abundant, ubiquitous, and conserved protein which plays important roles in a number of biological processes. In the present study, the TCTP in shrimp Litopenaeus vannamei was analyzed. The TCTP of L.vannamei, a 168-amino-acid polypeptide, shares a high degree of similarity with TCTPs from other species, having two TCTP protein signatures at the 45-55 aa and 123-145 aa motif. The mRNA and protein levels from different tissues were detected with the highest in muscle and the lowest in heart among all examined tissues. In addition, temporal TCTP expression was significantly up-regulated at 16 h and 48 h following infection with white spot syndrome virus (WSSV. Lastly, silencing of TCTP with dsRNA led to a significant increase of WSSV loads. These results provide new insights into the importance of TCTP as an evolutionarily conserved molecule for shrimp innate immunity against virus infection.

  18. Modern View on Microbiocenosis, Immune Response and Factors Influencing on Their Formation. Fundamental and Applied Aspects

    Directory of Open Access Journals (Sweden)

    N. M. Bogdanova

    2013-01-01

    Full Text Available This review of current literature summarizes results of scientific studies on the structure of the intestinal microbiota both of adults and infants. It is shown, that all intestinal microbiota of an adult consists of 395 phylogenetically isolated groups of microorganisms, among them 244 are absolutely new. Based on the RNA-sequencing of genes the most common among Caucasians enterotypes were detected. It was demonstrated, that specific structure of intestinal microbiota of an adult individual is unique and stable and that genetic background of the macroorganism is a base of intestinal microbiome formation. The article covers the issues of special characteristics of microbiocenosis development at the early stages of ontogenesis. It is emphasized, that prevalence of «infantile» species of bifidobacteria in the structure of intestinal microbiota of breast-fed infants is due to the presence of certain nutritive substances in the milk: oligosaccharides of the breast milk, which are natural prebiotics. The authors give criteria for including the nutrients into the group of prebiotics and show new experimental and clinical data on influence of prebiotics on different levels of immunological defense system.Key words: intestinal microbiota, enterotypes, prebiotics, oligosaccharides, inulin, immune response.

  19. The Serratia LuxR family regulator CarR 39006 activates transcription independently of cognate quorum sensing signals.

    Science.gov (United States)

    Poulter, Simon; Carlton, Timothy M; Spring, David R; Salmond, George P C

    2011-05-01

    In Gram-negative bacteria, quorum sensing control of gene expression is mediated by transcription factors of the LuxR family, whose DNA-binding affinity is modulated by diffusible N-acyl homoserine lactone (AHL) signalling molecules. In Serratia sp. ATCC 39006 and the plant pathogen Erwinia carotovora ssp. carotovora (Ecc), the biosynthesis of the β-lactam antibiotic 1-carbapen-2-em-3-carboxylic acid (Car) is under quorum sensing control. This study has revealed that, uniquely, the LuxR family transcriptional activator CarR(39006) from Serratia 39006 has no detectable affinity for cognate AHL molecules. Furthermore, CarR(39006) was shown to be naturally competent to bind to its target promoter with high affinity, activate transcription and resist cellular proteolysis, and was unaffected by AHL signals. Experiments with chimeric proteins suggest that the C-terminal DNA-binding domain of CarR(39006) may be responsible for conferring AHL independence. In contrast, we show that the homologous CarR(Ecc) protein binds to its 3O-C6-HSL ligand with high affinity, and that the highly conserved Trp-44 residue is critical for this interaction. Unlike TraR from Agrobacterium tumefaciens, CarR(Ecc) is not directly protected from cellular proteolysis by AHL binding, but via AHL-induced DNA binding. At physiological protein concentrations, AHL binding induces CarR(Ecc) to bind to its target promoter with higher affinity and activate transcription. © 2011 Blackwell Publishing Ltd.

  20. Generation of T-follicular helper cells in vitro: requirement for BCR cross-linking and cognate B- and T-cell interaction.

    Science.gov (United States)

    Kolenbrander, Anne; Grewe, Bastian; Nemazee, David; Überla, Klaus; Temchura, Vladimir

    2017-09-07

    The minimal requirements for in vitro modeling of the natural CD4(+) T-cell differentiation into T follicular helper (TFH) cells are still under investigation. We co-cultured wild type and TCR-transgenic CD4(+) T-cells from naïve mice with dendritic cells and BCR-transgenic B-cells in the presence of HIV-derived virus-like particles containing matched B- and T-cell epitopes. This co-culturing induced co-expression of TFH-master regulator transcription factor BCL-6 and CXCR5 in up to 10% of the wild type and up to 40% of the TCR-transgenic CD4(+) T-cells. Phenotypic markers, production of IL-21 and isotype switching of the B-cells to IgG1 further indicated a helper function of the induced TFH-cells in vitro. Dendritic cells supported the generation of functional TFH-cells, but were unable to induce them without cognate B-cells. Thus, our study presents a robust experimental system for efficient generation of functionally active TFH-cells in vitro and confirms the importance of cognate B- and T-cell cross-talk for the TFH differentiation process. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. Interferon-¿- and tumour necrosis factor-a-producing cells in humans who are immune to cutaneous leishmaniasis

    DEFF Research Database (Denmark)

    Kemp, K; Theander, T G; Hviid, L

    1999-01-01

    living in an area without the disease. The production of interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and interleukin (IL)-10 was investigated in culture supernatants, and the cellular sources of IFN-gamma and TNF-alpha were identified. Cells from individuals with a history of cutaneous...... leishmaniasis produced significantly higher levels of IFN-gamma and TNF-alpha than cells from individuals without a history of the disease. Similar levels of IL-10 were found in the two groups. Flow cytometric analysis revealed high numbers of CD3+ cells producing IFN-gamma and TNF-alpha, and only a few CD3......+ cells containing IL-10, in the PBMC cultures from the individuals with a history of cutaneous leishmaniasis. Interferon-gamma and TNF-alpha were predominantly produced by CD4+ T cells rather than CD8+ T cells. The results suggest that cellular immunity against cutaneous leishmaniasis is mediated...

  2. Immune recognition and processing of blood coagulation factor VIII by antigen-presenting cells

    NARCIS (Netherlands)

    van Haren, S.D.

    2011-01-01

    Hemophilia A is an X chromosome-linked bleeding disorder caused by a reduction or com­plete absence of coagulation factor VIII (FVIII). The bleeding tendency in patients suffering from hemophilia A can be treated by regular intravenous administrations of FVIII. A severe complication that occurs in

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

    Science.gov (United States)

    Sulaiman, Azad A.; Zolnierczyk, Katarzyna; Japa, Ornampai; Owen, Jonathan P.; Maddison, Ben C.; Hodgkinson, Jane E.; Gough, Kevin C.

    2016-01-01

    The trematode Fasciola hepatica is responsible for chronic zoonotic infection globally. Despite causing a potent T-helper 2 response, it is believed that potent immunomodulation is responsible for rendering this host reactive non-protective host response thereby allowing the parasite to remain long-lived. We have previously identified a growth factor, FhTLM, belonging to the TGF superfamily can have developmental effects on the parasite. Herein we demonstrate that FhTLM can exert influence over host immune functions in a host receptor specific fashion. FhTLM can bind to receptor members of the Transforming Growth Factor (TGF) superfamily, with a greater affinity for TGF-β RII. Upon ligation FhTLM initiates the Smad2/3 pathway resulting in phenotypic changes in both fibroblasts and macrophages. The formation of fibroblast CFUs is reduced when cells are cultured with FhTLM, as a result of TGF-β RI kinase activity. In parallel the wound closure response of fibroblasts is also delayed in the presence of FhTLM. When stimulated with FhTLM blood monocyte derived macrophages adopt an alternative or regulatory phenotype. They express high levels interleukin (IL)-10 and arginase-1 while displaying low levels of IL-12 and nitric oxide. Moreover they also undergo significant upregulation of the inhibitory receptor PD-L1 and the mannose receptor. Use of RNAi demonstrates that this effect is dependent on TGF-β RII and mRNA knock-down leads to a loss of IL-10 and PD-L1. Finally, we demonstrate that FhTLM aids newly excysted juveniles (NEJs) in their evasion of antibody-dependent cell cytotoxicity (ADCC) by reducing the NO response of macrophages—again dependent on TGF-β RI kinase. FhTLM displays restricted expression to the F. hepatica gut resident NEJ stages. The altered fibroblast responses would suggest a role for dampened tissue repair responses in facilitating parasite migration. Furthermore, the adoption of a regulatory macrophage phenotype would allow for a reduced

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

    Directory of Open Access Journals (Sweden)

    Azad A Sulaiman

    2016-11-01

    Full Text Available The trematode Fasciola hepatica is responsible for chronic zoonotic infection globally. Despite causing a potent T-helper 2 response, it is believed that potent immunomodulation is responsible for rendering this host reactive non-protective host response thereby allowing the parasite to remain long-lived. We have previously identified a growth factor, FhTLM, belonging to the TGF superfamily can have developmental effects on the parasite. Herein we demonstrate that FhTLM can exert influence over host immune functions in a host receptor specific fashion. FhTLM can bind to receptor members of the Transforming Growth Factor (TGF superfamily, with a greater affinity for TGF-β RII. Upon ligation FhTLM initiates the Smad2/3 pathway resulting in phenotypic changes in both fibroblasts and macrophages. The formation of fibroblast CFUs is reduced when cells are cultured with FhTLM, as a result of TGF-β RI kinase activity. In parallel the wound closure response of fibroblasts is also delayed in the presence of FhTLM. When stimulated with FhTLM blood monocyte derived macrophages adopt an alternative or regulatory phenotype. They express high levels interleukin (IL-10 and arginase-1 while displaying low levels of IL-12 and nitric oxide. Moreover they also undergo significant upregulation of the inhibitory receptor PD-L1 and the mannose receptor. Use of RNAi demonstrates that this effect is dependent on TGF-β RII and mRNA knock-down leads to a loss of IL-10 and PD-L1. Finally, we demonstrate that FhTLM aids newly excysted juveniles (NEJs in their evasion of antibody-dependent cell cytotoxicity (ADCC by reducing the NO response of macrophages-again dependent on TGF-β RI kinase. FhTLM displays restricted expression to the F. hepatica gut resident NEJ stages. The altered fibroblast responses would suggest a role for dampened tissue repair responses in facilitating parasite migration. Furthermore, the adoption of a regulatory macrophage phenotype would allow

  5. Identification of immunity-related genes in prostate cancer and potential role of the ETS family of transcription factors in their regulation.

    Science.gov (United States)

    Shaikhibrahim, Zaki; Lindstrot, Andreas; Ellinger, Jörg; Rogenhofer, Sebastian; Buettner, Reinhard; Wernert, Nicolas

    2011-11-01

    The role of the immune response in tumor progression, and disease outcome is still debated, and a lack of knowledge of the immune defenses in prostate cancer still exists. In addition, the ETS family of transcription factors which is involved in translocations frequently found in prostate cancer is reported to be essential for the regulation of immunity-related genes. In order to identify immunity-related genes in prostate cancer, we performed two microarrays using RNA extracted from laser microdissected glands of the normal prostate proper (or the peripheral zone) and moderately and poorly differentiated prostate carcinomas from patients who had undergone radical prostatectomy. Many differentially expressed genes were found, however, only immunity-related genes (B cell, innate, and T cell immunity) with an expression of more than 10-fold increase or decrease and a Pimmunity-related genes in prostate cancer, and provided insights into their potential regulation, which may lead to a better early detection, immunotherapy, and therapeutic drug treatment of this disease. Unraveling the dynamics of the ETS-immunity-related genes will provide an invaluable insight into understanding prostate cancer immunology.

  6. Staphylococcus aureus surface protein SdrE binds complement regulator factor H as an immune evasion tactic.

    Directory of Open Access Journals (Sweden)

    Julia A Sharp

    Full Text Available Similar to other highly successful invasive bacterial pathogens, Staphylococcus aureus recruits the complement regulatory protein factor H (fH to its surface to inhibit the alternative pathway of complement. Here, we report the identification of the surface-associated protein SdrE as a fH-binding protein using purified fH overlay of S. aureus fractionated cell wall proteins and fH cross-linking to S. aureus followed by mass spectrometry. Studies using recombinant SdrE revealed that rSdrE bound significant fH whether from serum or as a purified form, in both a time- and dose-dependent manner. Furthermore, rSdrE-bound fH exhibited cofactor functionality for factor I (fI-mediated cleavage of C3b to iC3b which correlated positively with increasing amounts of fH. Expression of SdrE on the surface of the surrogate bacterium Lactococcus lactis enhanced recruitment of fH which resulted in increased iC3b generation. Moreover, surface expression of SdrE led to a reduction in C3-fragment deposition, less C5a generation, and reduced killing by polymorphonuclear cells. Thus, we report the first identification of a S. aureus protein associated with the staphylococcal surface that binds factor H as an immune evasion mechanism.

  7. Orthographic processing in balanced bilingual children: Cross-language evidence from cognates and false friends.

    Science.gov (United States)

    Schröter, Pauline; Schroeder, Sascha

    2016-01-01

    We investigated whether beginning bilingual readers activate orthographic as well as semantic representations in both of their languages while reading in one of them. Balanced bilingual third graders who were learning to read concurrently in German and English completed two lexical decision tasks, one in each language, including cognates, false friends, and matched control words. Results showed a processing advantage for cognates over controls in both languages, indicating that the facilitation effect is driven by the level of balanced language proficiency rather than by experience with print. Except for lower accuracy scores in German, false friends did not differ in their processing from controls, pointing to the presence of semantic-to-orthographic feedback already in the beginning of reading acquisition. Confirming assumptions by the bilingual interactive activation plus (BIA+) model as well as the revised hierarchical model (RHM), findings suggest that in their strategy to resolve orthographic ambiguity, balanced bilingual children are more comparable to bilingual adults than to child second-language (L2) learners. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Dynamic Patterns of Systemic Innate Immunity and Inflammatory Associated Factors in Experimental Caprine Coccidiosis.

    Science.gov (United States)

    Tadayon, Shabnam; Razavi, Seyed Mostafa; Nazifi, Saeed

    2016-12-01

    The present study was designed to assess the dynamic patterns of pro-inflammatory cytokines, including IFN-γ, TNF-α, IL-4, IL-6, acute phase protein (α1-acid-glycoprotein, AGP), and an inflammation associated factor (adenosine deaminase; ADA) following experimental caprine coccidiosis. Ten kids aging from 2 to 4 months were infected orally with 5×10(4) sporulated oocysts and 10 animals served as controls. Blood samples were collected in both groups before infection and at days 3, 7, 14, 21, 28, and 35 post-infection (PI), and the levels of above-mentioned factors were measured. IFN-γ, TNF-α, IL-4, IL-6, AGP, and ADA activities were significantly higher in infected animals from day 7 PI (Pcoccidiosis.

  9. Tumor and Host Factors Controlling Antitumor Immunity and Efficacy of Cancer Immunotherapy.

    Science.gov (United States)

    Spranger, Stefani; Sivan, Ayelet; Corrales, Leticia; Gajewski, Thomas F

    2016-01-01

    Despite recent clinical advances in immunotherapy, a fraction of cancer patients fails to respond to these interventions. Evidence from preclinical mouse models as well as clinical samples has provided evidence that the extent of activated T cell infiltration within the tumor microenvironment is associated with clinical response to immunotherapies including checkpoint blockade. Therefore, understanding the molecular mechanisms mediating the lack of T cell infiltration into the tumor microenvironment will be instrumental for the development of new therapeutic strategies to render those patients immunotherapy responsive. Recent data have suggested that major sources of intersubject heterogeneity include differences in somatic mutations in specific oncogene pathways between cancers of individual subjects and also environmental factors including commensal microbial composition. Successful identification of such causal factors should lead to new therapeutic approaches that may facilitate T cell entry into noninflamed tumors and expand the fraction of patients capable of responding to novel immunotherapies.

  10. Receptor-like kinase complexes in plant innate immunity.

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    Christiaan eGreeff

    2012-08-01

    Full Text Available Receptor-like kinases (RLKs are surface localized, transmembrane receptors comprising a large family of well-studied kinases. RLKs signal through their transmembrane and juxtamembrane domains with the aid of various interacting partners and downstream components. The N-terminal extracellular domain defines ligand specificity, and RLK families are sub-classed according to this domain. The most studied of these subfamilies include those with 1 leucine rich repeat (LRR domains, 2 LysM domains (LYM and 3 the Catharanthus roseus RLK1-like (CrRLK1L domain. These proteins recognize distinct ligands of microbial origin or ligands derived from intracellular protein/carbohydrate signals. For example, the pattern recognition receptor (PRR AtFLS2 recognizes flg22 from flagellin, and the PRR AtEFR recognizes elf18 from elongation factor (EF-Tu. Upon binding of their cognate ligands, the aforementioned RLKs activate generic immune responses termed pattern triggered immunity (PTI. RLKs can form complexes with other family members and engage a variety of intracellular signaling components and regulatory pathways upon stimulation. This review focuses on interesting new data about how these receptors form protein complexes to exert their function.

  11. Dynamic Patterns of Systemic Innate Immunity and Inflammatory Associated Factors in Experimental Caprine Coccidiosis

    Science.gov (United States)

    Tadayon, Shabnam; Razavi, Seyed Mostafa; Nazifi, Saeed

    2016-01-01

    The present study was designed to assess the dynamic patterns of pro-inflammatory cytokines, including IFN-γ, TNF-α, IL-4, IL-6, acute phase protein (α1-acid-glycoprotein, AGP), and an inflammation associated factor (adenosine deaminase; ADA) following experimental caprine coccidiosis. Ten kids aging from 2 to 4 months were infected orally with 5×104 sporulated oocysts and 10 animals served as controls. Blood samples were collected in both groups before infection and at days 3, 7, 14, 21, 28, and 35 post-infection (PI), and the levels of above-mentioned factors were measured. IFN-γ, TNF-α, IL-4, IL-6, AGP, and ADA activities were significantly higher in infected animals from day 7 PI (P<0.05). In conclusion, the circulatory levels of most systemic inflammatory markers, including pro-inflammatory cytokines (IFN-γ, TNF-α, IL-4, IL-6), AGP, and ADA increased significantly starting from day 3 to day 7 PI in caprine coccidiosis. PMID:28095656

  12. Skin innate immune system

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    Berna Aksoy

    2013-06-01

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

  13. Streptococcal 5'-Nucleotidase A (S5nA), a Novel Streptococcus pyogenes Virulence Factor That Facilitates Immune Evasion.

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    Zheng, Lisa; Khemlani, Adrina; Lorenz, Natalie; Loh, Jacelyn M S; Langley, Ries J; Proft, Thomas

    2015-12-25

    Streptococcus pyogenes is an important human pathogen that causes a wide range of diseases. Using bioinformatics analysis of the complete S. pyogenes strain SF370 genome, we have identified a novel S. pyogenes virulence factor, which we termed streptococcal 5'-nucleotidase A (S5nA). A recombinant form of S5nA hydrolyzed AMP and ADP, but not ATP, to generate the immunomodulatory molecule adenosine. Michaelis-Menten kinetics revealed a Km of 169 μm and a Vmax of 7550 nmol/mg/min for the substrate AMP. Furthermore, recombinant S5nA acted synergistically with S. pyogenes nuclease A to generate macrophage-toxic deoxyadenosine from DNA. The enzyme showed optimal activity between pH 5 and pH 6.5 and between 37 and 47 °C. Like other 5'-nucleotidases, S5nA requires divalent cations and was active in the presence of Mg(2+), Ca(2+), or Mn(2+). However, Zn(2+) inhibited the enzymatic activity. Structural modeling combined with mutational analysis revealed a highly conserved catalytic dyad as well as conserved substrate and cation-binding sites. Recombinant S5nA significantly increased the survival of the non-pathogenic bacterium Lactococcus lactis during a human whole blood killing assay in a dose-dependent manner, suggesting a role as an S. pyogenes virulence factor. In conclusion, we have identified a novel S. pyogenes enzyme with 5'-nucleotidase activity and immune evasion properties.

  14. [Changes of acquired immune deficiency syndrome related knowledge, attitudes, behaviors and their influencing factors among college students in Beijing].

    Science.gov (United States)

    2017-06-18

    To compare acquired immune deficiency syndrome (AIDS) related knowledge, attitudes, behaviors and their influencing factors among college students in different years in Beijing, and to provide evidence for targeted health education among college students in future. College students were selected by the stratified cluster sampling method, and a questionnaire survey was conducted among college students in year 2006 and 2016 in Beijing. The sample sizes were 1 800 and 3 001 college students, respectively. The contents of the questionnaire included: socio-demographic characteristics, AIDS related knowledge, AIDS related attitude, sex intercourse and its related risk behaviors, condom use intension, and AIDS related health education. Compared with the year 2006, the average AIDS knowledge scores of college students in year 2016 dropped from 12.78±1.95 to 11.90±2.56 (t=12.91, Pinfluencing factors of intention on condom use were male (OR=0.713), self-efficacy of condom purchase (OR=0.876), never received sex education before college (OR=0.752), self-efficacy of condom use (OR=1.135), belief of condom use (OR=1.775), and attitude towards AIDS patients (OR=1.136). AIDS related knowledge, attitudes and behaviors among college students have been changed, AIDS related health education should be designed and improved based on new characteristics of college students. AIDS health education in colleges should pay more attention to sex attitude and sex responsibility and self-protection awareness among college students as well.

  15. PD98059 Influences Immune Factors and Enhances Opioid Analgesia in Model of Neuropathy.

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    Ewelina Rojewska

    Full Text Available Neuropathic pain treatment remains challenging due to ineffective therapy and resistance to opioid analgesia. Mitogen-activated protein kinase kinase (MAPKK have been identified as the crucial regulators of pro- and antinociceptive factors. We used PD98059, an inhibitor of the MAPKK family members MEK1/2. The aim of study was to examine the influence of single and/or repeated PD98059 on nociception and opioid effectiveness in neuropathy. Moreover, we examined how PD98059 influences selected members of cellular pathways and cytokines. The PD98059 (2.5 mcg was intrathecally preemptively administered before chronic constriction injury (CCI, and then once daily for 7 days. Additionally, at day 7 after CCI the PD98059-treated rats received a single injection of opioids. Using Western blot and qRT-PCR techniques in PD98059-treated rats we analyzed the mRNA and/or protein level of p38, ERK1/2, JNK, NF-kappaB, IL-1beta, IL-6, iNOS and IL-10 in the lumbar spinal cord. Our results indicate that PD98059 has an analgesic effects and potentiates morphine and/or buprenorphine analgesia. Parallel we observed that PD98059 inhibit upregulation of the CCI-elevated p38, ERK1/2, JNK and NF-kappaB protein levels. Moreover, PD98059 also prevented increase of pro- (IL-1beta, IL-6, and iNOS but enhances anti-nociceptive (IL-10 factors. Summing up, PD98059 diminished pain and increased the effectiveness of opioids in neuropathy. The inhibition of MEKs might inactivate a variety of cell signaling pathways that are implicated in nociception.

  16. PD98059 Influences Immune Factors and Enhances Opioid Analgesia in Model of Neuropathy.

    Science.gov (United States)

    Rojewska, Ewelina; Popiolek-Barczyk, Katarzyna; Kolosowska, Natalia; Piotrowska, Anna; Zychowska, Magdalena; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

    2015-01-01

    Neuropathic pain treatment remains challenging due to ineffective therapy and resistance to opioid analgesia. Mitogen-activated protein kinase kinase (MAPKK) have been identified as the crucial regulators of pro- and antinociceptive factors. We used PD98059, an inhibitor of the MAPKK family members MEK1/2. The aim of study was to examine the influence of single and/or repeated PD98059 on nociception and opioid effectiveness in neuropathy. Moreover, we examined how PD98059 influences selected members of cellular pathways and cytokines. The PD98059 (2.5 mcg) was intrathecally preemptively administered before chronic constriction injury (CCI), and then once daily for 7 days. Additionally, at day 7 after CCI the PD98059-treated rats received a single injection of opioids. Using Western blot and qRT-PCR techniques in PD98059-treated rats we analyzed the mRNA and/or protein level of p38, ERK1/2, JNK, NF-kappaB, IL-1beta, IL-6, iNOS and IL-10 in the lumbar spinal cord. Our results indicate that PD98059 has an analgesic effects and potentiates morphine and/or buprenorphine analgesia. Parallel we observed that PD98059 inhibit upregulation of the CCI-elevated p38, ERK1/2, JNK and NF-kappaB protein levels. Moreover, PD98059 also prevented increase of pro- (IL-1beta, IL-6, and iNOS) but enhances anti-nociceptive (IL-10) factors. Summing up, PD98059 diminished pain and increased the effectiveness of opioids in neuropathy. The inhibition of MEKs might inactivate a variety of cell signaling pathways that are implicated in nociception.

  17. PD98059 Influences Immune Factors and Enhances Opioid Analgesia in Model of Neuropathy

    Science.gov (United States)

    Rojewska, Ewelina; Popiolek-Barczyk, Katarzyna; Kolosowska, Natalia; Piotrowska, Anna; Zychowska, Magdalena; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

    2015-01-01

    Neuropathic pain treatment remains challenging due to ineffective therapy and resistance to opioid analgesia. Mitogen-activated protein kinase kinase (MAPKK) have been identified as the crucial regulators of pro- and antinociceptive factors. We used PD98059, an inhibitor of the MAPKK family members MEK1/2. The aim of study was to examine the influence of single and/or repeated PD98059 on nociception and opioid effectiveness in neuropathy. Moreover, we examined how PD98059 influences selected members of cellular pathways and cytokines. The PD98059 (2.5 mcg) was intrathecally preemptively administered before chronic constriction injury (CCI), and then once daily for 7 days. Additionally, at day 7 after CCI the PD98059-treated rats received a single injection of opioids. Using Western blot and qRT-PCR techniques in PD98059-treated rats we analyzed the mRNA and/or protein level of p38, ERK1/2, JNK, NF-kappaB, IL-1beta, IL-6, iNOS and IL-10 in the lumbar spinal cord. Our results indicate that PD98059 has an analgesic effects and potentiates morphine and/or buprenorphine analgesia. Parallel we observed that PD98059 inhibit upregulation of the CCI-elevated p38, ERK1/2, JNK and NF-kappaB protein levels. Moreover, PD98059 also prevented increase of pro- (IL-1beta, IL-6, and iNOS) but enhances anti-nociceptive (IL-10) factors. Summing up, PD98059 diminished pain and increased the effectiveness of opioids in neuropathy. The inhibition of MEKs might inactivate a variety of cell signaling pathways that are implicated in nociception. PMID:26426693

  18. Cysteine proteinase from Streptococcus pyogenes enables evasion of innate immunity via degradation of complement factors.

    Science.gov (United States)

    Honda-Ogawa, Mariko; Ogawa, Taiji; Terao, Yutaka; Sumitomo, Tomoko; Nakata, Masanobu; Ikebe, Kazunori; Maeda, Yoshinobu; Kawabata, Shigetada

    2013-05-31

    Streptococcus pyogenes is an important human pathogen that causes invasive diseases such as necrotizing fasciitis, sepsis, and streptococcal toxic shock syndrome. We investigated the function of a major cysteine protease from S. pyogenes that affects the amount of C1-esterase inhibitor (C1-INH) and other complement factors and aimed to elucidate the mechanism involved in occurrence of streptococcal toxic shock syndrome from the aspect of the complement system. First, we revealed that culture supernatant of a given S. pyogenes strain and recombinant SpeB degraded the C1-INH. Then, we determined the N-terminal sequence of the C1-INH fragment degraded by recombinant SpeB. Interestingly, the region containing one of the identified cleavage sites is not present in patients with C1-INH deficiency. Scanning electron microscopy of the speB mutant incubated in human serum showed the abnormal superficial architecture and irregular oval structure. Furthermore, unlike the wild-type strain, that mutant strain showed lower survival capacity than normal as compared with heat-inactivated serum, whereas it had a significantly higher survival rate in serum without the C1-INH than in normal serum. Also, SpeB degraded multiple complement factors and the membrane attack complex. Flow cytometric analyses revealed deposition of C9, one of the components of membrane the attack complex, in greater amounts on the surface of the speB mutant, whereas lower amounts of C9 were bound to the wild-type strain surface. These results suggest that SpeB can interrupt the human complement system via degrading the C1-INH, thus enabling S. pyogenes to evade eradication in a hostile environment.

  19. Immune tolerance induced by platelet-targeted factor VIII gene therapy in hemophilia A mice is CD4 T cell mediated.

    Science.gov (United States)

    Chen, Y; Luo, X; Schroeder, J A; Chen, J; Baumgartner, C K; Hu, J; Shi, Q

    2017-10-01

    Essentials The immune response is a significant concern in gene therapy. Platelet-targeted gene therapy can restore hemostasis and induce immune tolerance. CD4 T cell compartment is tolerized after platelet gene therapy. Preconditioning regimen affects immune tolerance induction in platelet gene therapy. Background Immune responses are a major concern in gene therapy. Our previous studies demonstrated that platelet-targeted factor VIII (FVIII) (2bF8) gene therapy together with in vivo drug selection of transduced cells can rescue the bleeding diathesis and induce immune tolerance in FVIII(null) mice. Objective To investigate whether non-selectable 2bF8 lentiviral vector (LV) for the induction of platelet-FVIII expression is sufficient to induce immune tolerance and how immune tolerance is induced after 2bF8LV gene therapy. Methods Platelet-FVIII expression was introduced by 2bF8LV transduction and transplantation. FVIII assays and tail bleeding tests were used to confirm the success of platelet gene therapy. Animals were challenged with rhF8 to explore if immune tolerance was induced after gene therapy. Treg cell analysis, T-cell proliferation assay and memory B-cell-mediated ELISPOT assay were used to investigate the potential mechanisms of immune tolerance. Results We showed that platelet-FVIII expression was sustained and the bleeding diathesis was restored in FVIII(null) mice after 2bF8LV gene therapy. None of the transduced recipients developed anti-FVIII inhibitory antibodies in the groups preconditioned with 660 cGy irradiation or busulfan plus ATG treatment even after rhF8 challenge. Treg cells significantly increased in 2bF8LV-transduced recipients and the immune tolerance developed was transferable. CD4(+) T cells from treated animals failed to proliferate in response to rhF8 re-stimulation, but memory B cells could differentiate into antibody secreting cells in 2bF8LV-transduced recipients. Conclusion 2bF8LV gene transfer without in vivo selection of

  20. Cross-linguistic transfer effects after phonologically based cognate therapy in a case of multilingual specific language impairment (SLI).

    Science.gov (United States)

    Kambanaros, Maria; Michaelides, Michalis; Grohmann, Kleanthes K

    2017-05-01

    Clinicians globally recognize as exceptionally challenging the development of effective intervention practices for bi- or multilingual children with specific language impairment (SLI). Therapy in both or all of an impaired child's languages is rarely possible. An alternative is to develop treatment protocols that facilitate the transfer of therapy effects from a treated language to an untreated language. To explore whether cognates, words that share meaning and phonological features across languages, could be used to boost lexical retrieval in the context of multilingual SLI. This is dependent on exploiting the phonological information in the one, trained language as a mechanism for (phonological) language transfer to the other, untrained languages. The participant is an 8.5-year-old girl diagnosed with SLI who showed a severe naming deficit in her three spoken languages (Bulgarian, English and Greek). She received training on cognates (n = 20) using a picture-based naming task in English only, three times a week, over a 4-week period for 20 min each time. Phonological-based naming therapy was carried out using form-based strategies. There was a significant improvement during therapy and immediately after intervention on cognate performance in English which was maintained 1 month after intervention. Cognate production in Bulgarian and Greek also improved during all stages of the intervention. Improvement in the non-treated languages was slightly more than half of the improvement recorded in English. The findings reflected some degree of cross-linguistic transfer effects. Cross-linguistic transfer effects were evident during therapy and after therapy had finished and the effects were maintained 1 month post-treatment. Both the native language (Bulgarian) and the dominant language (Greek) benefitted equally from the treatment of cognates in English. Generalization to non-treatment words was evident, predominantly for English. The results suggest that cognates can

  1. The DAF-16/FOXO transcription factor functions as a regulator of epidermal innate immunity.

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    Cheng-Gang Zou

    Full Text Available The Caenorhabditis elegans DAF-16 transcription factor is critical for diverse biological processes, particularly longevity and stress resistance. Disruption of the DAF-2 signaling cascade promotes DAF-16 activation, and confers resistance to killing by pathogenic bacteria, such as Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. However, daf-16 mutants exhibit similar sensitivity to these bacteria as wild-type animals, suggesting that DAF-16 is not normally activated by these bacterial pathogens. In this report, we demonstrate that DAF-16 can be directly activated by fungal infection and wounding in wild-type animals, which is independent of the DAF-2 pathway. Fungal infection and wounding initiate the Gαq signaling cascade, leading to Ca(2+ release. Ca(2+ mediates the activation of BLI-3, a dual-oxidase, resulting in the production of reactive oxygen species (ROS. ROS then activate DAF-16 through a Ste20-like kinase-1/CST-1. Our results indicate that DAF-16 in the epidermis is required for survival after fungal infection and wounding. Thus, the EGL-30-Ca(2+-BLI-3-CST-1-DAF-16 signaling represents a previously unknown pathway to regulate epidermal damage response.

  2. Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection.

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    Yee Suan Poo

    2014-12-01

    Full Text Available The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. Herein we highlight the propensity of CHIKV infections to persist long term, both as persistent, steady-state, viraemias in multiple B cell deficient mouse strains, and as persistent RNA (including negative-strand RNA in wild-type mice. The knockout mouse studies provided evidence for a role for T cells (but not NK cells in viraemia suppression, and confirmed the role of T cells in arthritis promotion, with vaccine-induced T cells also shown to be arthritogenic in the absence of antibody responses. However, MHC class II-restricted T cells were not required for production of anti-viral IgG2c responses post CHIKV infection. The anti-viral cytokines, TNF and IFNγ, were persistently elevated in persistently infected B and T cell deficient mice, with adoptive transfer of anti-CHIKV antibodies unable to clear permanently the viraemia from these, or B cell deficient, mice. The NOD background increased viraemia and promoted arthritis, with B, T and NK deficient NOD mice showing high-levels of persistent viraemia and ultimately succumbing to encephalitic disease. In wild-type mice persistent CHIKV RNA and negative strand RNA (detected for up to 100 days post infection was associated with persistence of cellular infiltrates, CHIKV antigen and stimulation of IFNα/β and T cell responses. These studies highlight that, secondary to antibodies, several factors are involved in virus control, and suggest that chronic arthritic disease is a consequence of persistent, replicating and transcriptionally active CHIKV RNA.

  3. Bioinformatics analysis of the factors controlling type I IFN gene expression in autoimmune disease and virus-induced immunity

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    Di eFeng

    2013-09-01

    Full Text Available Patients with systemic lupus erythematosus (SLE and Sjögren's syndrome (SS display increased levels of type I IFN-induced genes. Plasmacytoid dendritic cells (PDCs are natural interferon producing cells and considered to be a primary source of IFN-α in these two diseases. Differential expression patterns of type I IFN inducible transcripts can be found in different immune cell subsets and in patients with both active and inactive autoimmune disease. A type I IFN gene signature generally consists of three groups of IFN-induced genes - those regulated in response to virus-induced type I IFN, those regulated by the IFN-induced mitogen-activated protein kinase/extracellular-regulated kinase (MAPK/ERK pathway, and those by the IFN-induced phosphoinositide-3 kinase (PI-3K pathway. These three groups of type I IFN-regulated genes control important cellular processes such as apoptosis, survival, adhesion, and chemotaxis, that when dysregulated, contribute to autoimmunity. With the recent generation of large datasets in the public domain from next-generation sequencing and DNA microarray experiments, one can perform detailed analyses of cell type-specific gene signatures as well as identify distinct transcription factors that differentially regulate these gene signatures. We have performed bioinformatics analysis of data in the public domain and experimental data from our lab to gain insight into the regulation of type I IFN gene expression. We have found that the genetic landscape of the IFNA and IFNB genes are occupied by transcription factors, such as insulators CTCF and cohesin, that negatively regulate transcription, as well as IRF5 and IRF7, that positively and distinctly regulate IFNA subtypes. A detailed understanding of the factors controlling type I IFN gene transcription will significantly aid in the identification and development of new therapeutic strategies targeting the IFN pathway in autoimmune disease.

  4. Decidual soluble factors, through modulation of dendritic cells functions, determine the immune response patterns at the feto-maternal interface.

    Science.gov (United States)

    Ahmadabad, Hasan Namdar; Salehnia, Mojdeh; Saito, Shigeru; Moazzeni, Seyed Mohammad

    2016-04-01

    Dendritic cells (DCs) can acquire immunogenic or tolerogenic properties depending on intrinsic and tissue environmental factors. We aimed to determine the immunomodulatory effects of decidual soluble factors from abortion- and non-abortion-prone mice on DC functions. The decidual cell supernatants (DS) were obtained from abortion-prone and non-abortion-prone mice. Splenic DCs were treated with DS and conalbumin (as an antigen) and injected into the palms of the mice. After five days, regional lymph node cells were collected and cultured in the presence and absence of conalbumin. The proliferation of lymphocyte cells, the frequency of regulatory T cells (Tregs), and the production of IL-4 and IFN-γ were measured by [(3)H]thymidine incorporation, flow cytometry, and ELISA respectively. Our results indicated that DS from both abortion- and non-abortion-prone mice decreased the ability of DCs to induce lymphocyte proliferation and IFN-γ production, while enhanced their capacity to induce Tregs compared with non-treated DCs. Another important finding was that the immunosuppressive effects of DS from abortion-prone mice on DCs for inducing proliferative responses, developing Tregs, and producing IFN-γ by primed lymphocytes was less than DS from non-abortion-prone mice. We also found that only DS from non-abortion-prone mice could enhance the capacity of DCs to induce IL-4 production by primed lymphocytes. It can be concluded that decidua-secreted factors, by altering DC functions, can determine the pattern of immune responses at the fetomaternal interface and, subsequently, pregnancy outcome. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. An exploratory qualitative assessment of factors influencing childhood vaccine providers' intention to recommend immunization in the Netherlands

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    Mollema Liesbeth

    2012-02-01

    Full Text Available Abstract Background Under the Dutch national immunization program (NIP, childhood vaccination is not mandatory, but its recommendation by childhood vaccine providers (CVP is important for maintaining high vaccination coverage. We therefore examined factors related to providers' intentions to recommend vaccinations to parents of young children. Methods We conducted four focus group discussions with nurses and physicians who provide vaccines to children 0-4 years old in diverse regions of the Netherlands. Three groups represented CVPs at child welfare centers (CWCs serving the general population, with the fourth representing anthroposophical CWCs. Elements of the Theory of Planned Behaviour (TPB were used to design the groups; thematic analysis was used to structure and analyze the dataset. Results Four main themes emerged, including 1 perceived responsibility: to promote vaccines and discuss pros and cons with parents (although this was usually not done if parents readily accepted the vaccination; 2 attitudes toward the NIP: mainly positive, but doubts as to NIP plans to vaccinate against diseases with a low perceived burden; 3 organizational factors: limited time and information can hamper discussions with parents; 4 relationship with parents: crucial and based mainly on communication to establish trust. Compared to CVPs at standard CWCs, the anthroposophical CWCs spent more time communicating and were more willing to adapt the NIP to individual cases. Conclusions Our qualitative assessment provides an overview of beliefs associated with providers' intention to recommend vaccinations. They were motivated to support the NIP, but their intentions to recommend vaccinations were affected by the perceived relevance of the vaccines, practical issues like limited time and by certain types of resistant parents. These results will inform future studies to test the magnitude and relative impact of these factors.

  6. related Factors of complete basic Immunization on children and Vaccine Management at Primary Health care and Health Post in X Subdistrict Depok city

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    Tri Afriani

    2015-01-01

    Full Text Available background:Immunization is an effective primary prevention against infectious diseases on children. The purpose of this study was to determine the related factors to the completeness of basic immunization on children and vaccine management at primary health care and posyandu in X Subdistric, Depok City. Methods:The study used a cross-sectional design with a sample of 140 mothers of children aged at least 11 months, and qualitatif study about vaccines management. Mother and child data collection using questionnaires and child health card (Kartu Menuju Sehat in December 2012–May 2013. Vaccine management data was collected at 2 primary health care and 2 posyandu with interview and observation. Data analysis was performed with Chi-square test. result:The largest percentage of mothers who have children under the age of at least 11 months of age <30 years, at least graduated from junior high school education, no work, have a low knowledge about immunization. Vaccine management in clinics and neighborhood health center for storage after use of vaccines in posyandu not be returned to the community health center, recording and reporting is not done on the book of the records so that the possibility of scattered or lost, and the person in charge of managing the vaccine instead of pharmacy personnel. Residual use of the vaccine in posyandu not directly returned to the health center. Recording the use of vaccines in posyandu not carried on the books, so it is probable scattered or lost. Manager vaccine at primary health care should a technical pharmacy in accordance with Government Regulation No. 51 of 2009 conclusion: Completeness of basic immunization of children under one years old (82,9%, incomplete biggest measles immunization (15,0%. Factors parental characteristics (age, education, occupation, knowledge and the availability of the vaccine were not significantly associated with children complete basic immunization. recommendation: Improving health

  7. Structurally well-defined macrophage activating factor derived from vitamin D3-binding protein has a potent adjuvant activity for immunization.

    Science.gov (United States)

    Yamamoto, N; Naraparaju, V R

    1998-06-01

    Freund's adjuvant produced severe inflammation that augments development of antibodies. Thus, mixed administration of antigens with adjuvant was not required as long as inflammation was induced in the hosts. Since macrophage activation for phagocytosis and antigen processing is the first step of antibody development, inflammation-primed macrophage activation plays a major role in immune development. Therefore, macrophage activating factor should act as an adjuvant for immunization. The inflammation-primed macrophage activation process is the major macrophage activating cascade that requires participation of serum vitamin D3-binding protein (DBP; human DBP is known as Gc protein) and glycosidases of B and T lymphocytes. Stepwise incubation of Gc protein with immobilized beta-galactosidase and sialidase efficiently generated the most potent macrophage activating factor (designated GcMAF) we have ever encountered. Administration of GcMAF (20 or 100 pg/mouse) resulted in stimulation of the progenitor cells for extensive mitogenesis and activation of macrophages. Administration of GcMAF (100 pg/mouse) along with immunization of mice with sheep red blood cells (SRBC) produced a large number of anti-SRBC antibody secreting splenic cells in 2-4 days. Thus, GcMAF has a potent adjuvant activity for immunization. Although malignant tumours are poorly immunogenic, 4 days after GcMAF-primed immunization of mice with heat-killed Ehrlich ascites tumour cells, the ascites tumour was no longer transplantable in these mice.

  8. Homologous and cross-reactive immune responses to enterotoxigenic Escherichia coli colonization factors in Bangladeshi children.

    Science.gov (United States)

    Qadri, Firdausi; Ahmed, Firoz; Ahmed, Tanvir; Svennerholm, Ann-Mari

    2006-08-01

    We have studied homologous (HoM) and cross-reacting (CR) immunoglobulin A (IgA) antibody responses to colonization factors (CFs) in Bangladeshi children with diarrhea due to enterotoxigenic E. coli (ETEC) strains of the CF antigen I (CFA/I) group (CFA/I, n = 25; coli surface antigen 4 [CS4], n = 8; CS14, n = 11) and the CS5 group (CS5, n = 15; CS7, n = 8), respectively. The responses to the HoM, CR, and heterologous (HeT) CF antigens in each group of patient were studied and compared to that seen in healthy children (n = 20). In the CFA/I group (CFA/I and CS14), patients responded with antibody-secreting cell (ASC) responses to HoM CFs (geometric mean, 156 to 329 ASCs/10(6) peripheral blood mononuclear cells [PBMCs]) and to CR CFs ( approximately 15 to 38 ASCs/10(6) PBMCs) but least of all to the HeT CS5 antigen (2 to 4 ASCs/10(6) PBMCs). For the CS5 group of patients with ETEC (CS5 and CS7), likewise, responses to HoM CFs (230 to 372 ASCs/10(6) PBMCs) and CR CFs (27 to 676 ASCs/10(6) PBMCs) were seen, along with lower responses to the HeT CFA/I antigen (9 to 38 ASCs/10(6) PBMCs). Both groups of patients responded with CF-specific IgA antibodies to HoM and CR antigens in plasma but responded less to the HeT CFs. The responses in patients were seen very soon after the onset of diarrhea and peaked around 1 week after onset. Vaccinees who had received two doses of the oral, killed whole-cell ETEC vaccine (CF-BS-ETEC) responded with plasma IgA antibodies to CFA/I, a component of the vaccine, but also to the CR CS14 antigen, which was not included in the vaccine, showing that antibody responses can be stimulated by a CFA/I-containing ETEC vaccine to a CR-reacting antigen in individuals in countries where ETEC is endemic.

  9. Risk factors for increased immune reconstitution in response to Mycobacterium tuberculosis antigens in tuberculosis HIV-infected, antiretroviral-naïve patients.

    Science.gov (United States)

    da Silva, Tatiana Pereira; Giacoia-Gripp, Carmem Beatriz Wagner; Schmaltz, Carolina A; Sant'Anna, Flavia Marinho; Saad, Maria Helena; Matos, Juliana Arruda de; de Lima E Silva, Julio Castro Alves; Rolla, Valeria Cavalcanti; Morgado, Mariza Gonçalves

    2017-09-06

    Little is known regarding the restoration of the specific immune response after combined antiretroviral therapy (cART) and anti-tuberculosis (TB) therapy introduction among TB-HIV patients. In this study, we examined the immune response of TB-HIV patients to Mycobacterium tuberculosis (Mtb) antigens to evaluate the response dynamics to different antigens over time. Moreover, we also evaluated the influence of two different doses of efavirenz and the factors associated with immune reconstitution. This is a longitudinal study nested in a clinical trial, where cART was initiated during the baseline visit (D0), which occurred 30 ± 10 days after the introduction of anti-TB therapy. Follow-up visits were performed at 30, 60, 90 and 180 days after cART initiation. The production of IFN-γ upon in vitro stimulation with Mtb antigens purified protein derivative (PPD), ESAT-6 and 38 kDa/CFP-10 using ELISpot was examined at baseline and follow-up visits. Sixty-one patients, all ART-naïve, were selected and included in the immune reconstitution analysis; seven (11.5%) developed Immune Reconstitution Inflammatory Syndrome (IRIS). The Mtb specific immune response was higher for the PPD antigen followed by 38 kDa/CFP-10 and increased in the first 60 days after cART initiation. In multivariate analysis, the variables independently associated with increased IFN-γ production in response to PPD antigen were CD4(+) T cell counts <200 cells/mm(3) at baseline, age, site of tuberculosis, 800 mg efavirenz dose and follow-up CD4(+) T cell counts. Moreover, the factors associated with the production of IFN-γ in response to 38 kDa/CFP-10 were detectable HIV viral load (VL) and CD4(+) T cell counts at follow-up visits of ≥200 cells/mm(3). These findings highlight the differences in immune response according to the specificity of the Mtb antigen, which contributes to a better understanding of TB-HIV immunopathogenesis. IFN-γ production elicited by PPD and 38 kDa/CFP-10

  10. T Cell Factor 1-Expressing Memory-like CD8(+) T Cells Sustain the Immune Response to Chronic Viral Infections.

    Science.gov (United States)

    Utzschneider, Daniel T; Charmoy, Mélanie; Chennupati, Vijaykumar; Pousse, Laurène; Ferreira, Daniela Pais; Calderon-Copete, Sandra; Danilo, Maxime; Alfei, Francesca; Hofmann, Maike; Wieland, Dominik; Pradervand, Sylvain; Thimme, Robert; Zehn, Dietmar; Held, Werner

    2016-08-16

    Chronic infections promote the terminal differentiation (or "exhaustion") of T cells and are thought to preclude the formation of memory T cells. In contrast, we discovered a small subpopulation of virus-specific CD8(+) T cells that sustained the T cell response during chronic infections. These cells were defined by, and depended on, the expression of the transcription factor Tcf1. Transcriptome analysis revealed that this population shared key characteristics of central memory cells but lacked an effector signature. Unlike conventional memory cells, Tcf1-expressing T cells displayed hallmarks of an "exhausted" phenotype, including the expression of inhibitory receptors such as PD-1 and Lag-3. This population was crucial for the T cell expansion that occurred in response to inhibitory receptor blockade during chronic infection. These findings identify a memory-like T cell population that sustains T cell responses and is a prime target for therapeutic interventions to improve the immune response in chronic infections. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. The expanding roles of the Sd(a)/Cad carbohydrate antigen and its cognate glycosyltransferase B4GALNT2.

    Science.gov (United States)

    Dall'Olio, Fabio; Malagolini, Nadia; Chiricolo, Mariella; Trinchera, Marco; Harduin-Lepers, Anne

    2014-01-01

    The histo-blood group antigens are carbohydrate structures present in tissues and body fluids, which contribute to the definition of the individual immunophenotype. One of these, the Sd(a) antigen, is expressed on the surface of erythrocytes and in secretions of the vast majority of the Caucasians and other ethnic groups. We describe the multiple and unsuspected aspects of the biology of the Sd(a) antigen and its biosynthetic enzyme β1,4-N-acetylgalactosaminyltransferase 2 (B4GALNT2) in various physiological and pathological settings. The immunodominant sugar of the Sd(a) antigen is a β1,4-linked N-acetylgalactosamine (GalNAc). Its cognate glycosyltransferase B4GALNT2 displays a restricted pattern of tissue expression, is regulated by unknown mechanisms - including promoter methylation, and encodes at least two different proteins, one of which with an unconventionally long cytoplasmic portion. In different settings, the Sd(a) antigen plays multiple and unsuspected roles. 1) In colon cancer, its dramatic down-regulation plays a potential role in the overexpression of sialyl Lewis antigens, increasing metastasis formation. 2) It is involved in the lytic function of murine cytotoxic T lymphocytes. 3) It prevents the development of muscular dystrophy in various dystrophic murine models, when overexpressed in muscular fibers. 4) It regulates the circulating half-life of the von Willebrand factor (vWf), determining the onset of a bleeding disorder in a murine model. The expression of the Sd(a) antigen has a wide impact on the physiology and the pathology of different biological systems. © 2013.

  12. Age-associated decrease in GDNF and its cognate receptor GFRα-1 protein expression in human skin.

    Science.gov (United States)

    Adly, Mohamed A; Assaf, Hanan A; Hussein, Mahmoud Rezk Abdelwahed

    2016-06-01

    Glial cell line-derived neurotrophic factor (GDNF) and its cognate receptor (GFRα-1) are expressed in normal human skin. They are involved in murine hair follicle morphogenesis and cycling control. We hypothesize that 'GDNF and GFRα-1 protein expression in human skin undergoes age-associated alterations. To test our hypothesis, the expression of these proteins was examined in human skin specimens obtained from 30 healthy individuals representing three age groups: children (5-18 years), adults (19-60 years) and the elderly (61-81 years). Immunofluorescent and light microscopic immunohistologic analyses were performed using tyramide signal amplification and avidin-biotin complex staining methods respectively. GDNF mRNA expression was examined by RT-PCR analysis. GDNF mRNA and protein as well as GFRα-1 protein expressions were detected in normal human skin. We found significantly reduced epidermal expression of these proteins with ageing. In the epidermis, the expression was strong in the skin of children and declined gradually with ageing, being moderate in adults and weak in the elderly. In children and adults, the expression of both GDNF and GFRα-1 proteins was strongest in the stratum basale and decreased gradually towards the surface layers where it was completely absent in the stratum corneum. In the elderly, GDNF and GFRα-1 protein expression was confined to the stratum basale. In the dermis, both GDNF and GFRα-1 proteins had strong expressions in the fibroblasts, sweat glands, sebaceous glands, hair follicles and blood vessels regardless of the age. Thus there is a decrease in epidermal GDNF and GFRα-1 protein expression in normal human skin with ageing. Our findings suggest that the consequences of this is that GFRα-1-mediated signalling is altered during the ageing process. The clinical and therapeutic ramifications of these observations mandate further investigations.

  13. Activating transcription factor 4 underlies the pathogenesis of arsenic trioxide-mediated impairment of macrophage innate immune functions.

    Science.gov (United States)

    Srivastava, Ritesh K; Li, Changzhao; Wang, Yong; Weng, Zhiping; Elmets, Craig A; Harrod, Kevin S; Deshane, Jessy S; Athar, Mohammad

    2016-10-01

    Chronic arsenic exposure to humans is considered immunosuppressive with augmented susceptibility to several infectious diseases. The exact molecular mechanisms, however, remain unknown. Earlier, we showed the involvement of unfolded protein response (UPR) signaling in arsenic-mediated impairment of macrophage functions. Here, we show that activating transcription factor 4 (ATF4), a UPR transcription factor, regulates arsenic trioxide (ATO)-mediated dysregulation of macrophage functions. In ATO-treated ATF4(+/+) wild-type mice, a significant down-regulation of CD11b expression was associated with the reduced phagocytic functions of peritoneal and lung macrophages. This severe immuno-toxicity phenotype was not observed in ATO-treated ATF4(+/-) heterozygous mice. To confirm these observations, we demonstrated in Raw 264.7 cells that ATF4 knock-down rescues ATO-mediated impairment of macrophage functions including cytokine production, bacterial engulfment and clearance of engulfed bacteria. Sustained activation of ATF4 by ATO in macrophages induces apoptosis, while diminution of ATF4 expression protects against ATO-induced apoptotic cell death. Raw 264.7 cells treated with ATO also manifest dysregulated Ca(++) homeostasis. ATO induces Ca(++)-dependent calpain-1 and caspase-12 expression which together regulated macrophage apoptosis. Additionally, apoptosis was also induced by mitochondria-regulated pathway. Restoring ATO-impaired Ca(++) homeostasis in ER/mitochondria by treatments with the inhibitors of inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC) attenuate innate immune functions of macrophages. These studies identify a novel role for ATF4 in underlying pathogenesis of macrophage dysregulation and immuno-toxicity of arsenic.

  14. Defining terminally differentiating B cell populations in rainbow trout immune tissues using the transcription factor XbpI.

    Science.gov (United States)

    Barr, Maggie; Mott, Katrina; Zwollo, Patty

    2011-12-01

    The nature of antibody-secreting cells in the rainbow trout is poorly defined. Here we describe a flow cytometric approach to help differentiate between four major trout B cell subsets present during terminal B cell differentiation: resting B cells, activated B cells, plasmablasts, and plasma cells. To aid in the identification of B cell subsets, the LPS-inducible transcription factor XbpI-S was used as a marker. An antibody specific to the stable form of inducible transcription factor X-box protein I (XbpI) was generated, which detects XbpI-S protein expression for species within the Oncorhyncus genus, including rainbow trout. Combinatorial expression patterns, or B cell signatures, were established using antibodies to XbpI-S, Pax5, and IgM in combination with a proliferation marker. We show that XbpI-S induction in trout splenic B cells increases throughout a 10-day in vitro LPS-induction period and that increased XbpI-S expression correlates with increased HCmu expression in the cell. PBLs displayed a lower level of XbpI-S induction during this incubation period, compared to spleen. We conclude that trout B cells follow a highly conserved B cell activation pathway, albeit slower than what has been observed in mammalian species. The use of XbpI-S as an activation marker for trout humoral immune activation promises to be useful for future in vivo studies, and can be applied to a broad range of teleost species. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. On the Contribution of Protein Spatial Organization to the Physicochemical Interconnection between Proteins and Their Cognate mRNAs.

    Science.gov (United States)

    Beier, Andreas; Zagrovic, Bojan; Polyansky, Anton A

    2014-01-01

    Early-stage evolutionary development of the universal genetic code remains a fundamental, open problem. One of the possible scenarios suggests that the code evolved in response to direct interactions between peptides and RNA oligonucleotides in the primordial environment. Recently, we have revealed a strong matching between base-binding preferences of modern protein sequences and the composition of their cognate mRNA coding sequences. These results point directly at the physicochemical foundation behind the code's origin, but also support the possibility of direct complementary interactions between proteins and their cognate mRNAs, especially if the two are unstructured. Here, we analyze molecular-surface mapping of knowledge-based amino-acid/nucleobase interaction preferences for a set of complete, high-resolution protein structures and show that the connection between the two biopolymers could remain relevant even for structured, folded proteins. Specifically, protein surface loops are strongly enriched in residues with a high binding propensity for guanine and cytosine, while adenine- and uracil-preferring residues are uniformly distributed throughout protein structures. Moreover, compositional complementarity of cognate protein and mRNA sequences remains strong even after weighting protein sequence profiles by residue solvent exposure. Our results support the possibility that protein/mRNA sequence complementarity may also translate to cognate interactions between structured biopolymers.

  16. Cross-Linguistic Transfer of Morphological Awareness in Spanish-Speaking English Language Learners: The Facilitating Effect of Cognate Knowledge

    Science.gov (United States)

    Ramirez, Gloria; Chen, Xi; Pasquarella, Adrian

    2013-01-01

    Cross-language effects of Spanish derivational awareness on English vocabulary and reading comprehension were studied in Spanish-speaking English Language Learners (N = 90) in grades four and seven. The role of cognate vocabulary in cross-language transfer of derivational awareness was also examined. Multivariate path analyses controlling for age,…

  17. Cross-Linguistic Transfer of Morphological Awareness in Spanish-Speaking English Language Learners: The Facilitating Effect of Cognate Knowledge

    Science.gov (United States)

    Ramirez, Gloria; Chen, Xi; Pasquarella, Adrian

    2013-01-01

    Cross-language effects of Spanish derivational awareness on English vocabulary and reading comprehension were studied in Spanish-speaking English Language Learners (N = 90) in grades four and seven. The role of cognate vocabulary in cross-language transfer of derivational awareness was also examined. Multivariate path analyses controlling for age,…

  18. Using Spanish-English Cognates in Children's Choices Picture Books to Develop Latino English Learners' Linguistic Knowledge

    Science.gov (United States)

    Hernández, Anita C.; Montelongo, José A.; Herter, Roberta J.

    2016-01-01

    Educators can take advantage of Latino English learners' linguistic backgrounds by teaching Spanish-English cognate vocabulary using the Children's Choices picture books. Cognates are words that have identical or nearly identical spellings and meanings in two languages because of their Latin and Greek origins. Students can learn to recognize…

  19. Using Spanish-English Cognates in Children's Choices Picture Books to Develop Latino English Learners' Linguistic Knowledge

    Science.gov (United States)

    Hernández, Anita C.; Montelongo, José A.; Herter, Roberta J.

    2016-01-01

    Educators can take advantage of Latino English learners' linguistic backgrounds by teaching Spanish-English cognate vocabulary using the Children's Choices picture books. Cognates are words that have identical or nearly identical spellings and meanings in two languages because of their Latin and Greek origins. Students can learn to recognize…

  20. Expression of microRNAs and innate immune factor genes in lung tissue of pigs infected with influenza virus (H1N2)

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Cirera, S.; Vasby, D.

    Swine influenza is a highly infectious respiratory disease in pigs caused by influenza A virus. Activation of a frontline of pattern-recognition receptors (PRRs) expressed by epithelial cells as well as immune cells of the upper respiratory tract, leads to a potent type 1 interferon (IFN) release...... A infection. The present work aimed of providing a better understanding of the involvement of innate immune factors including miRNA in the host response to establishment and progression of influenza virus infection. Twenty pigs were challenged by aerosol containing H1N2 (A/swine/Denmark/12687/03) influenza......, this response must be tightly regulated. Recently, microRNA (miRNA) has been proposed to play an important role in modulating and fine tuning the innate immune response in order to avoid such harmful overreactions. Little is known about the significance of miRNA regulation in the lung during acute influenza...

  1. Novel positive regulatory role for the SPL6 transcription factor in the N TIR-NB-LRR receptor-mediated plant innate immunity.

    Directory of Open Access Journals (Sweden)

    Meenu S Padmanabhan

    2013-03-01

    Full Text Available Following the recognition of pathogen-encoded effectors, plant TIR-NB-LRR immune receptors induce defense signaling by a largely unknown mechanism. We identify a novel and conserved role for the SQUAMOSA PROMOTER BINDING PROTEIN (SBP-domain transcription factor SPL6 in enabling the activation of the defense transcriptome following its association with a nuclear-localized immune receptor. During an active immune response, the Nicotiana TIR-NB-LRR N immune receptor associates with NbSPL6 within distinct nuclear compartments. NbSPL6 is essential for the N-mediated resistance to Tobacco mosaic virus. Similarly, the presumed Arabidopsis ortholog AtSPL6 is required for the resistance mediated by the TIR-NB-LRR RPS4 against Pseudomonas syringae carrying the avrRps4 effector. Transcriptome analysis indicates that AtSPL6 positively regulates a subset of defense genes. A pathogen-activated nuclear-localized TIR-NB-LRR like N can therefore regulate defense genes through SPL6 in a mechanism analogous to the induction of MHC genes by mammalian immune receptors like CIITA and NLRC5.

  2. Incidence, clinical spectrum, risk factors and impact of HIV-associated immune reconstitution inflammatory syndrome in South Africa.

    Directory of Open Access Journals (Sweden)

    Lewis John Haddow

    Full Text Available BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS is a widely recognised complication of antiretroviral therapy (ART, but there are still limited data from resource-limited settings. Our objective was to characterize the incidence, clinical spectrum, risk factors and contribution to mortality of IRIS in two urban ART clinics in South Africa. METHODS AND FINDINGS: 498 adults initiating ART in Durban, South Africa were followed prospectively for 24 weeks. IRIS diagnosis was based on consensus expert opinion, and classified by mode of presentation (paradoxical worsening of known opportunistic infection [OI] or unmasking of subclinical disease. 114 patients (22.9% developed IRIS (36% paradoxical, 64% unmasking. Mucocutaneous conditions accounted for 68% of IRIS events, mainly folliculitis, warts, genital ulcers and herpes zoster. Tuberculosis (TB accounted for 25% of IRIS events. 18/135 (13.3% patients with major pre-ART OIs (e.g. TB, cryptococcosis developed paradoxical IRIS related to the same OI. Risk factors for this type of IRIS were baseline viral load >5.5 vs. 30 days of OI treatment prior to ART (2.66; 1.16-6.09. Unmasking IRIS related to major OIs occurred in 25/498 patients (5.0%, and risk factors for this type of IRIS were baseline C-reactive protein ≥25 vs. 12 g/dL (3.36; 1.32-8.52, ≥10% vs. <10% weight loss prior to ART (2.31; 1.05-5.11 and mediastinal lymphadenopathy on pre-ART chest x-ray (9.15; 4.10-20.42. IRIS accounted for 6/25 (24% deaths, 13/65 (20% hospitalizations and 10/35 (29% ART interruptions or discontinuations. CONCLUSION: IRIS occurred in almost one quarter of patients initiating ART, and accounted for one quarter of deaths in the first 6 months. Priority strategies to reduce IRIS-associated morbidity and mortality in ART programmes include earlier ART initiation before onset of advanced immunodeficiency, improved pre-ART screening for TB and cryptococcal infection, optimization of OI therapy prior to ART

  3. In vivo expansion of regulatory T cells with IL-2/IL-2 mAb complexes prevents anti-factor VIII immune responses in hemophilia A mice treated with factor VIII plasmid-mediated gene therapy.

    Science.gov (United States)

    Liu, Chao-Lien; Ye, Peiqing; Yen, Benjamin C; Miao, Carol H

    2011-08-01

    Generation of transgene-specific immune responses can constitute a major complication following gene therapy treatment. An in vivo approach to inducing selective expansion of Regulatory T (Treg) cells by injecting interleukin-2 (IL-2) mixed with a specific IL-2 monoclonal antibody (JES6-1) was adopted to modulate anti-factor VIII (anti-FVIII) immune responses. Three consecutive IL-2 complexes treatments combined with FVIII plasmid injection prevented anti-FVIII formation and achieved persistent, therapeutic-level of FVIII expression in hemophilia A (HemA) mice. The IL-2 complexes treatment expanded CD4(+)CD25(+)Foxp3(+) Treg cells five- to sevenfold on peak day, and they gradually returned to normal levels within 7-14 days without changing other lymphocyte populations. The transiently expanded Treg cells are highly activated and display suppressive function in vitro. Adoptive transfer of the expanded Treg cells protected recipient mice from generation of high-titer antibodies following FVIII plasmid challenge. Repeated plasmid transfer is applicable in tolerized mice without eliciting immune responses. Mice treated with IL-2 complexes mounted immune responses against both T-dependent and T-independent neoantigens, indicating that IL-2 complexes did not hamper the immune system for long. These results demonstrate the important role of Treg cells in suppressing anti-FVIII immune responses and the potential of developing Treg cell expansion therapies that induce long-term tolerance to FVIII.

  4. Staphylococcal Ecb protein and host complement regulator factor H enhance functions of each other in bacterial immune evasion.

    Science.gov (United States)

    Amdahl, Hanne; Jongerius, Ilse; Meri, Taru; Pasanen, Tanja; Hyvärinen, Satu; Haapasalo, Karita; van Strijp, Jos A; Rooijakkers, Suzan H; Jokiranta, T Sakari

    2013-08-15

    Staphylococcus aureus is a major human pathogen causing more than a tenth of all septicemia cases and often superficial and deep infections in various tissues. One of the immune evasion strategies of S. aureus is to secrete proteins that bind to the central complement opsonin C3b. One of these, extracellular complement binding protein (Ecb), is known to interfere directly with functions of C3b. Because C3b is also the target of the physiological plasma complement regulator, factor H (FH), we studied the effect of Ecb on the complement regulatory functions of FH. We show that Ecb enhances acquisition of FH from serum onto staphylococcal surfaces. Ecb and FH enhance mutual binding to C3b and also the function of each other in downregulating complement activation. Both Ecb and the C-terminal domains 19-20 of FH bind to the C3d part of C3b. We show that the mutual enhancing effect of Ecb and FH on binding to C3b depends on binding of the FH domain 19 to the C3d part of C3b next to the binding site of Ecb on C3d. Our results show that Ecb, FH, and C3b form a tripartite complex. Upon exposure of serum-sensitive Haemophilus influenzae to human serum, Ecb protected the bacteria, and this effect was enhanced by the addition of the C-terminal domains 19-20 of FH. This finding indicates that the tripartite complex formation could give additional protection to bacteria and that S. aureus is thereby able to use host FH and bacterial Ecb in a concerted action to eliminate C3b at the site of infection.

  5. Lysophospholipid Growth Factors and Their G Protein-Coupled Receptors in Immunity, Coronary Artery Disease, and Cancer

    Directory of Open Access Journals (Sweden)

    Edward J. Goetzl

    2002-01-01

    Full Text Available The physiological lysophospholipids (LPLs, exemplified by lysophosphatidic acid (LPA and sphingosine 1-phosphate (S1P, are omnific mediators of normal cellular proliferation, survival, and functions. Although both LPA and S1P attain micromolar concentrations in many biological fluids, numerous aspects of their biosynthesis, transport, and metabolic degradation are unknown. Eight members of a new subfamily of G protein-coupled LPA/S1P receptors, originally termed Edg Rs, bind either LPA or S1P with high affinity and transduce a series of growth-related and/or cytoskeleton-based functional responses. The most critical areas of LPL biology and pathobiology are neural development and neurodegeneration, immunity, atherosclerosis and myocardial injury, and cancer. Data from analyses of T cells established two basic points: (1 the plasticity and adaptability of expression of LPA/S1P Rs by some cells as a function of activation, and (2 the role of opposing signals from two different receptors for the same ligand as a mechanism for fine control of effects of LPLs. In the heart, LPLs may promote coronary atherosclerosis, but are effectively cytoprotective for hypoxic cardiac myocytes and those exposed to oxygen free radicals. The findings of production of LPA by some types of tumor cells, overexpression of selected sets of LPA receptors by the same tumor cells, and augmentation of the effects of protein growth factors by LPA have suggested pathogenetic roles for the LPLs in cancer. The breadth of physiologic and pathologic activities of LPLs emphasizes the importance of developing bioavailable nonlipid agonists and antagonists of the LPA/S1P receptors for diverse therapeutic applications.

  6. Prevalence and socio-demographic factors associated with non-protective immunity against tetanus among high school adolescents girls in Nigeria

    Science.gov (United States)

    2014-01-01

    Background The low uptake of tetanus vaccine and its resultant high burden of tetanus in Nigeria suggest the need to improve routine and booster vaccination in children and adolescents. However, epidemiological evidence for vaccination in the adolescent age group needed for effective strategy and policy formulation is lacking. This study was carried out to determine the prevalence of protective immunity against tetanus and to identify risk factors for non-protective immunity among schooling adolescents. Methods Using a three-stage sampling technique, 851 female adolescents were randomly selected from secondary schools in Ibadan, Nigeria. A pre-tested questionnaire was used to obtain data on demographic and socio-economic characteristics and history of tetanus vaccination. An immuno-chromatographic rapid test kit, “Tetanos Quick Stick” was used to test specific anti-tetanus antibody protective level in venous blood samples. Descriptive statistics, Chi-square and logistic regression analyses were done with level of significance set at p = 0.05. Results Mean age of participants was 14.3 ± 1.9 years. Seroprevalence of protective immunity against tetanus was 38.1% and it significantly decreased with increasing age. More adolescents in public (65.4%) than private (44.7%) schools had non-protective level of immunity. A significantly increasing trend in the risk of non-protective immunity was observed with decreasing level of mothers’ education. Also, the Odds of non-protective level of immunity was significantly higher in public than private schools (OR = 2.14; 95% CI =1.39, 3.20) but lower among adolescents who had history of recent tetanus toxoid injection than those who did not (OR = 0.11 95% CI = 0.09, 0.22). However, no significant association was found between protective immunity against tetanus and parents’ marital status as well as family size. Conclusion Protective immunity against tetanus among female adolescents was poor, more so in public

  7. Prenatal immune challenge is an environmental risk factor for brain and behavior change relevant to schizophrenia: evidence from MRI in a mouse model.

    Directory of Open Access Journals (Sweden)

    Qi Li

    Full Text Available OBJECTIVES: Maternal infection during pregnancy increases risk of severe neuropsychiatric disorders, including schizophrenia and autism, in the offspring. The most consistent brain structural abnormality in patients with schizophrenia is enlarged lateral ventricles. However, it is unknown whether the aetiology of ventriculomegaly in schizophrenia involves prenatal infectious processes. The present experiments tested the hypothesis that there is a causal relationship between prenatal immune challenge and emergence of ventricular abnormalities relevant to schizophrenia in adulthood. METHOD: We used an established mouse model of maternal immune activation (MIA by the viral mimic PolyI:C administered in early (day 9 or late (day 17 gestation. Automated voxel-based morphometry mapped cerebrospinal fluid across the whole brain of adult offspring and the results were validated by manual region-of-interest tracing of the lateral ventricles. Parallel behavioral testing determined the existence of schizophrenia-related sensorimotor gating abnormalities. RESULTS: PolyI:C-induced immune activation, in early but not late gestation, caused marked enlargement of lateral ventricles in adulthood, without affecting total white and grey matter volumes. This early exposure disrupted sensorimotor gating, in the form of prepulse inhibition. Identical immune challenge in late gestation resulted in significant expansion of 4(th ventricle volume but did not disrupt sensorimotor gating. CONCLUSIONS: Our results provide the first experimental evidence that prenatal immune activation is an environmental risk factor for adult ventricular enlargement relevant to schizophrenia. The data indicate immune-associated environmental insults targeting early foetal development may have more extensive neurodevelopmental impact than identical insults in late prenatal life.

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

    DEFF Research Database (Denmark)

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

    1984-01-01

    The complement-mediated solubilization (CMS) of immune complexes (IC) and the initial kinetics (IKS) of this reaction in human sera depleted of or deficient in C2, C3, C8, factors B, P and I were investigated. Sera depleted of B or P and those lacking native C3 or factor I showed virtually no CMS...... by a radioassay and kinetic data for the binding of C3b to preformed immune complexes. The CMS capacity reached maximum at 39-41 degrees C and at an ionic strength of approximately 0.20 mu. Selective chelation of Mg2+ completely abolished the CMS of IC. Maximal CMS was observed at Mg2+ concentration of about 2m...

  9. Three transcription factors and the way immune cells affected by different plasma change in opposite ways in the development of the syndrome of pre-eclampsia

    Institute of Scientific and Technical Information of China (English)

    Liang Zhou; Zhu Jing; Wang Yunfei; Wang You; Zhang Yu; Lin Jianhua; Di Wen

    2014-01-01

    Background How the transcriptional factors regulated the innate and adaptive immune system in pregnancy and preeclampsia are less understood.Nevertheless,what the plasma work in the development of this disease was not sure.The present study was design to evaluate what the transcriptional factors change in innate and adaptive immune system and what the plasma do in this filed.Methods Peripheral blood mononuclear cells (PBMC) from non-pregnant women (n=18),women with clinically normal pregnancies (n=23) and women with pre-eclampsia (n=20) were separated from peripheral blood to isolate monocytes and T cells.The purity of monocytes and T cells were analysed by flow cytometry.Monocytes and T cells were stimulated in either lipopolysaccharides (LPS) or phorbol-myristate-acetate (PMA),respectively.Transcription Factor Arrays were used to screen the transcription factors of interest in comparing of different groups.PBMC were isolated from another 8 nonpregnant samples were co-incubated with different groups of plasma.Polymerase chain reaction (PCR) was performed using whole cell extractions of the samples.Results Nuclear factor of activated T-cells-1 (NFAT-1),signal transducers and activators of transcription-1 (STAT-1) and activator protein-1 (AP-1) are up-regulated in monocytes in pregnancy and more so in pre-eclampsia.On the the contrary,NFAT-1,STAT-1 and AP-1 are down-regulated in T cells in pregnancy and more so in pre-eclampsia.A reduction was observed in interferon (IFN)-y,interleukin (IL)-12 and IL-4 expression in T cells incubated with pre-eclamptic plasma.An elevation was observed in tumor necrosis factor (TNF)-α,IL-1 and IL-12 expression in monocytes incubated with preeclamptic plasma.Conclusions Innate immunity is over activated and adaptive immunity is over suppressed in the development of preeclampsia.NFAT-1,STAT-1 and AP-1 might be the central transcription factors in the pathogenesis of pre-eclampsia.They induced some changes in plasma and "educate" the

  10. Modulation of Anti-Tumor Necrosis Factor Alpha (TNF-α) Antibody Secretion in Mice Immunized with TNF-α Kinoid

    OpenAIRE

    Assier, Eric; Semerano, Luca; Duvallet, Emilie; Delavallée, Laure; Bernier, Emilie; Laborie, Marion; Grouard-Vogel, Géraldine; Larcier, Patrick; Bessis, Natacha; Boissier, Marie-Christophe

    2012-01-01

    Tumor necrosis factor alpha (TNF-α) blockade is an effective treatment for patients with TNF-α-dependent chronic inflammatory diseases, such as rheumatoid arthritis, Crohn's disease, and psoriasis. TNF-α kinoid, a heterocomplex of human TNF-α and keyhole limpet hemocyanin (KLH) (TNF-K), is an active immunotherapy targeting TNF-α. Since the TNF-K approach is an active immunization, and patients receiving this therapy also receive immunosuppressant treatment, we evaluated the effect of some imm...

  11. On the biogenesis of the myelin sheath: cognate polarized trafficking pathways in oligodendrocytes.

    Science.gov (United States)

    de Vries, H; Hoekstra, D

    2000-01-01

    Oligodendrocytes, the myelinating cells of the central nervous system, are capable of transporting vast quantities of proteins and of lipids, in particular galactosphingolipids, to the myelin sheath. The sheath is continuous with the plasma membrane of the oligodendrocyte, but the composition of both membrane domains differs substantially. Given its high glycosphingolipid and cholesterol content the myelin sheath bears similarity to the lipid composition of the apical domain of a polarized cell. The question thus arises whether myelin components, like typical apical membrane proteins are transported by an apical-like trafficking mechanism to the sheath, involving a 'raft'-mediated mechanism. Indeed, the evidence indicates the presence of cognate apical and basolateral pathways in oligodendrocytes. However, all major myelin proteins do not participate in this pathway, and remarkably apical-like trafficking seems to be restricted to the oligodendrocyte cell body. In this review, we summarize the evidence on the existence of different trafficking pathways in the oligodendrocyte, and discuss possible mechanisms separating the oligodendrocyte's membrane domains.

  12. EEVD motif of heat shock cognate protein 70 contributes to bacterial uptake by trophoblast giant cells

    Directory of Open Access Journals (Sweden)

    Kim Suk

    2009-12-01

    Full Text Available Abstract Background The uptake of abortion-inducing pathogens by trophoblast giant (TG cells is a key event in infectious abortion. However, little is known about phagocytic functions of TG cells against the pathogens. Here we show that heat shock cognate protein 70 (Hsc70 contributes to bacterial uptake by TG cells and the EEVD motif of Hsc70 plays an important role in this. Methods Brucella abortus and Listeria monocytogenes were used as the bacterial antigen in this study. Recombinant proteins containing tetratricopeptide repeat (TPR domains were constructed and confirmation of the binding capacity to Hsc70 was assessed by ELISA. The recombinant TPR proteins were used for investigation of the effect of TPR proteins on bacterial uptake by TG cells and on pregnancy in mice. Results The monoclonal antibody that inhibits bacterial uptake by TG cells reacted with the EEVD motif of Hsc70. Bacterial TPR proteins bound to the C-terminal of Hsc70 through its EEVD motif and this binding inhibited bacterial uptake by TG cells. Infectious abortion was also prevented by blocking the EEVD motif of Hsc70. Conclusions Our results demonstrate that surface located Hsc70 on TG cells mediates the uptake of pathogenic bacteria and proteins containing the TPR domain inhibit the function of Hsc70 by binding to its EEVD motif. These molecules may be useful in the development of methods for preventing infectious abortion.

  13. Synthetic protein scaffolds based on peptide motifs and cognate adaptor domains for improving metabolic productivity

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    Anselm H.C. Horn

    2015-11-01

    Full Text Available The efficiency of many cellular processes relies on the defined interaction among different proteins within the same metabolic or signaling pathway. Consequently, a spatial colocalization of functionally interacting proteins has frequently emerged during evolution. This concept has been adapted within the synthetic biology community for the purpose of creating artificial scaffolds. A recent advancement of this concept is the use of peptide motifs and their cognate adaptor domains. SH2, SH3, GBD, and PDZ domains have been used most often in research studies to date. The approach has been successfully applied to the synthesis of a variety of target molecules including catechin, D-glucaric acid, H2, hydrochinone, resveratrol, butyrate, gamma-aminobutyric acid, and mevalonate. Increased production levels of up to 77-fold have been observed compared to non-scaffolded systems. A recent extension of this concept is the creation of a covalent linkage between peptide motifs and adaptor domains, which leads to a more stable association of the scaffolded systems and thus bears the potential to further enhance metabolic productivity.

  14. Non-cognate translation priming in masked priming lexical decision experiments: A meta-analysis.

    Science.gov (United States)

    Wen, Yun; van Heuven, Walter J B

    2016-09-09

    The masked translation priming paradigm has been widely used in the last 25 years to investigate word processing in bilinguals. Motivated by studies reporting mixed findings, in particular for second language (L2) to first language (L1) translation priming, we conducted, for the first time in the literature, a meta-analysis of 64 masked priming lexical decision experiments across 24 studies to assess the effect sizes of L1-L2 and L2-L1 non-cognate translation priming effects in bilinguals. Our meta-analysis also investigated the influence of potential moderators of translation priming effects. The results provided clear evidence of significant translation priming effects for both directions, with L1-L2 translation priming significantly larger than L2-L1 translation priming (i.e., effect size of 0.86 vs. 0.31). The analyses also revealed that L1-L2 translation effect sizes were moderated by the interval between prime and target (ISI), whereas L2-L1 translation effect sizes were modulated by the number of items per cell. Theoretical and methodological implications of this meta-analysis are discussed and recommendations for future studies are provided.

  15. Observation of curative effect in antibiotics associated diarrhea children treated by pidotimod and the influence on the inflammation factors and the immune function

    Institute of Scientific and Technical Information of China (English)

    Zhao-Yang Yin; Yao Chen; Ting Zhao

    2016-01-01

    Objective:To explore the curative effect in antibiotics associated diarrhea children treated by pidotimod and the influence on the inflammation factors and the immune function.Methods:A total of 82 cases antibiotic associated diarrhea children were divided into control group and observation group according to random number table method,41 cases in each group, children in two groups were given conventional treatment, on this basis, children in observation group were with pidotimod treatment, they were treated for 2 weeks, compared the clinical efficacy and immune globulin: IgA, IgG, IgM, T cell subgroup: CD3+, CD4+, CD8+, CD4+/CD8+, and inflammation factors: tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6). Results:The total effective rate in control group was 75.61%,it was significantly lower than 95.12% in observation group; The levels of CD3+,CD4+,CD4+/CD8+, IgA, IgG after treatment in two groups were significantly rised while the levels of TNF-α, IL-6 were significantly reduced than before treatment, The amplitude of index above in observation group was greater than the control group, the difference were all statistically significant.Conclusion: The curative effect in antibiotics associated diarrhea children treated by pidotimodi is obvious, it can reduce inflammation, improve immunity.

  16. Word Naming in Bodo-Assamese Bilinguals: The Role of Semantic Context, Cognate Status, Second Language Age of Acquisition and Proficiency.

    Science.gov (United States)

    Kaur, Sugandha

    2017-04-12

    The current study investigated the effects of the semantic context, cognate status of the word and second language age of acquisition and proficiency in two word naming experiments (Experiment 1 and 2). Three groups of Bodo-Assamese bilinguals named cognate and non-cognate words in their first language, Bodo and second language, Assamese, which were presented in categorized and randomized lists. Experiment 1 demonstrated significant category interference for both cognate and non-cognate words; whereas, in Experiment 2, category interference was observed only in case of cognate words, indicating that naming in L2 was more prone to semantic effects. In Experiment 1, the magnitude of the category interference effect was larger for the low proficient bilinguals, but in Experiment 2, only the high proficient bilinguals demonstrated category interference effect. Further, cognate facilitation effect was not observed in both experiments which is in line with the findings of previous studies. The findings are discussed in light of the predictions of the Revised Hierarchical Model.

  17. T-helper I immunity, specific for the breast cancer antigen insulin-like growth factor-I receptor (IGF-IR), is associated with increased adiposity.

    Science.gov (United States)

    Cecil, Denise L; Park, Kyong Hwa; Gad, Ekram; Childs, Jennifer S; Higgins, Doreen M; Plymate, Stephen R; Disis, Mary L

    2013-06-01

    Numerous lines of evidence demonstrate that breast cancer is immunogenic; yet, there are few biologically relevant immune targets under investigation restricting the exploration of vaccines to limited breast cancer subtypes. Insulin-like growth factor-I receptor (IGF-IR) is a promising vaccine candidate since it is overexpressed in most breast cancer subtypes, is part of a dominant cancer growth pathway, and has been validated as a therapeutic target. We questioned whether IGF-IR was immunogenic in cancer patients. IGF-IR-specific IgG antibodies were significantly elevated in early-stage breast cancer patients at the time of diagnosis as compared to volunteer donors (p = 0.04). Predicted T-helper epitopes, derived from the IGF-IR extracellular and transmembrane domains, elicited a significantly higher incidence of Th2 immunity in breast cancer patients as compared to controls (p = 0.01). Moreover, the magnitude of Th2 immunity was greater in breast cancer patients compared to controls (p = 0.02). In contrast, both breast cancer patients and volunteer donors demonstrated a similar incidence of Th1 immunity to IGF-IR domains with the predominant response directed against epitopes in the intracellular domain of the protein. As the incidence of IGF-IR type I immunity was not associated with a breast cancer diagnosis, we questioned whether other factors were contributing to the presence of IGF-IR-specific T-cells in both populations. While age was not associated with Th1 immunity, we observed a significantly greater magnitude of IGF-IR IFN-γ-secreting T-cells in obese subjects as compared to overweight (p cancer diagnosis. No significant difference was observed for Th2 incidence or magnitude when stratified by age (p = 0.174, p = 0.966, respectively) or body mass index (p = 0.137, p = 0.174, respectively). Our data demonstrate that IGF-IR is a tumor antigen and IGF-IR-specific Th1 immunity may be associated with obesity rather than malignancy.

  18. Two-Component Signal Transduction Systems of Desulfovibrio Vulgaris: Structural and Phylogenetic Analysis and Deduction of Putative Cognate Pairs

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Weiwen; Culley, David E.; Wu, Gang; Brockman, Fred J.

    2006-01-20

    ABSTRACT-Two-component signal transduction systems (TCSTS) composed of sensory histidine kinases (HK) and response regulators (RR), constitute a key element of the mechanism by which bacteria sense and respond to changes in environments. A large number of TCSTSs including 59 putative HKs and 55 RRs were identified from the Desulfovibrio vulgaris genome, indicating their important roles in regulation of cellular metabolism. In this study, the structural and phylogenetic analysis of all putative TCSTSs in D. vulgaris was performed. The results showed D. vulgaris contained an unexpectedly large number of hybrid-type HKs, implying that multiple-step phosphorelay may be a common signal transduction mechanism in D. vulgaris. Most TCSTS components of D. vulgaris were found clustered into several subfamilies previously recognized in other bacteria and extensive co-evolution between D. vulgaris HKs and RRs was observed, suggesting that the concordance of HKs and RRs in cognate phylogenetic groups could be indicative of cognate TCSTSs...

  19. Exploring cognition processes in second language acquisition: the case of cognates and false-friends in EST

    Directory of Open Access Journals (Sweden)

    Pilar Durán Escribano

    2004-04-01

    Full Text Available This article explores one aspect of the processing perspective in L2 learning in an EST context: the processing of new content words, in English, of the type 'cognates' and 'false friends', by Spanish speaking engineering students. The paper does not try to offer a comprehensive overview of language acquisition mechanisms, but rather it is intended to review more narrowly how our conceptual systems, governed by intricately linked networks of neural connections in the brain, make language development possible, creating, at the same time, some L2 processing problems. The case of 'cognates' and 'false friends' in specialised contexts is brought here to illustrate some of the processing problems that the L2 learner has to confront, and how mappings in the visual, phonological and semantic (conceptual brain structures function in second language processing of new vocabulary.

  20. Cognate and noncognate metal ion coordination in metal-specific metallothioneins: the Helix pomatia system as a model.

    Science.gov (United States)

    Palacios, Oscar; Pérez-Rafael, Sílvia; Pagani, Ayelen; Dallinger, Reinhard; Atrian, Sílvia; Capdevila, Mercè

    2014-08-01

    The Helix pomatia metallothionein (MT) system, namely, its two highly specific forms, HpCdMT and HpCuMT, has offered once again an optimum model to study metal-protein specificity. The present work investigates the most unexplored aspect of the coordination behavior of MT polypeptides with respect to either cognate or noncognate metal ions, as opposed to the standard studies of cognate metal ion coordination. To this end, we analyzed the in vivo synthesis of the corresponding complexes with their noncognate metals, and we performed a detailed spectroscopic and spectrometric study of the Zn(2+)/Cd(2+) and Zn(2+)/Cu(+) in vitro replacement reactions on the initial Zn-HpMT species. An HpCuMTAla site-directed mutant, exhibiting differential Cu(+)-binding abilities in vivo, was also included in this study. We demonstrate that when an MT binds its cognate metal, it yields well-folded complexes of limited stoichiometry, representative of minimal-energy conformations. In contrast, the incorporation of noncognate metal ions is better attributed to an unspecific reaction of cysteinic thiolate groups with metal ions, which is dependent on their concentration in the surrounding milieu, where no minimal-energy structure is reached, and otherwise, the MT peptide acts as a multidentate ligand that will bind metal ions until its capacity has been saturated. Additionally, we suggest that previous binding of an MT polypeptide with its noncognate metal ion (e.g., binding of Zn(2+) to the HpCuMT isoform) may preclude the correct folding of the complex with its cognate metal ion.

  1. The 73 kilodalton heat shock cognate protein purified from rat brain contains nonesterified palmitic and stearic acids.

    Science.gov (United States)

    Guidon, P T; Hightower, L E

    1986-08-01

    A protein related to the 71 kilodalton inducible rat heat shock protein was purified to electrophoretic homogeneity in milligram amounts from brain tissue of nonheat-stressed rats. The protein has been designated as a stress cognate protein based on previous studies and data presented herein that this protein cross-reacted with a monoclonal antibody originally raised against the Drosophila 70 kilodalton heat shock protein. The purified protein had an apparent molecular mass of 73 kilodaltons when analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and an apparent mass of 150 kilodaltons as determined by nondissociative gel chromatography, suggesting that the purified protein is a homodimer. The purified protein had isoelectric points of 5.0 under nondissociative conditions and 5.6 when exposed to protein denaturants, suggesting loss of bound anionic molecules and/or net exposure of basic residues upon denaturation. Chloroform/methanol extraction of the purified protein and subsequent analyses by thin layer and gas-liquid chromatography resulted in the identification of palmitic and stearic acids noncovalently bound to the protein. Approximately four molecules of fatty acids were bound per dimer with palmitic and stearic acids present in a one-to-one ratio. The purified protein did not bind exogenously added radioactive palmitate, indicating that the fatty acid-binding sites of the cognate protein were fully occupied and that the associated fatty acids were too tightly bound to exchange readily. The possible significance of the fatty acids associated with the 73 kilodalton stress cognate protein is discussed.

  2. The Search for a Genetic Factor Associating with Immune Restoration Disease in HIV Patients Co-Infected with Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Jacquita S. Affandi

    2013-01-01

    Full Text Available BACKGROUND: Up to 43% of HIV-infected patients co-infected with Mycobacterium tuberculosis experience exacerbations of tuberculosis (TB after commencing antiretroviral therapy (ART. These are termed immune restoration disease (IRD. It is unclear why individual susceptibility varies.

  3. Cell-mediated immunity to histocompatibility antigens : controlling factors, with emphasis on Graft-versus-host reactions in mice

    NARCIS (Netherlands)

    H. Bril (Herman)

    1984-01-01

    textabstractGraft-versus-Host (GvH) disease is characterized by weight loss, diarrhea, skin lesions, hypofunction of the immune system with concomitant infections, etc. This syndrome is potentially lethal. GvH reactions, which underly this disease, may occur when immunocompetent T lymphocytes are tr

  4. Elongation Factor Tu and Heat Shock Protein 70 Are Membrane-Associated Proteins from Mycoplasma ovipneumoniae Capable of Inducing Strong Immune Response in Mice.

    Science.gov (United States)

    Jiang, Fei; He, Jinyan; Navarro-Alvarez, Nalu; Xu, Jian; Li, Xia; Li, Peng; Wu, Wenxue

    2016-01-01

    Chronic non-progressive pneumonia, a disease that has become a worldwide epidemic has caused considerable loss to sheep industry. Mycoplasma ovipneumoniae (M. ovipneumoniae) is the causative agent of interstitial pneumonia in sheep, goat and bighorn. We here have identified by immunogold and immunoblotting that elongation factor Tu (EF-Tu) and heat shock protein 70 (HSP 70) are membrane-associated proteins on M. ovipneumonaiea. We have evaluated the humoral and cellular immune responses in vivo by immunizing BALB/c mice with both purified recombinant proteins rEF-Tu and rHSP70. The sera of both rEF-Tu and rHSP70 treated BALB/c mice demonstrated increased levels of IgG, IFN-γ, TNF-α, IL-12(p70), IL-4, IL-5 and IL-6. In addition, ELISPOT assay showed significant increase in IFN-γ+ secreting lymphocytes in the rHSP70 group when compared to other groups. Collectively our study reveals that rHSP70 induces a significantly better cellular immune response in mice, and may act as a Th1 cytokine-like adjuvant in immune response induction. Finally, growth inhibition test (GIT) of M. ovipneumoniae strain Y98 showed that sera from rHSP70 or rEF-Tu-immunized mice inhibited in vitro growth of M. ovipneumoniae. Our data strongly suggest that EF-Tu and HSP70 of M. ovipneumoniae are membrane-associated proteins capable of inducing antibody production, and cytokine secretion. Therefore, these two proteins may be potential candidates for vaccine development against M. ovipneumoniae infection in sheep.

  5. Lack of Proinflammatory Cytokine Interleukin-6 or Tumor Necrosis Factor Receptor-1 Results in a Failure of the Innate Immune Response after Bacterial Meningitis

    Directory of Open Access Journals (Sweden)

    Lea-Jessica Albrecht

    2016-01-01

    Full Text Available The most frequent pathogen that causes bacterial meningitis is the Gram-positive bacterium Streptococcus pneumoniae. By entering the brain, host cells will be activated and proinflammatory cytokines like interleukin-6 (IL-6 and tumor necrosis factor-α (TNF-α are released. The goal of the current study was to examine the interaction between IL-6 and TNFR1 as receptor for TNF-α and the innate immune response in vivo in a model of Streptococcus pneumoniae-induced meningitis. For the experiments IL-6−/−, TNFR1−/−, and TNFR1-IL-6−/− KO mice were used. Our results revealed higher mortality rates and bacterial burden after infection in TNFR1−/−, IL-6−/−, and TNFR1-IL-6−/− mice and a decreased immune response including lower neutrophil infiltration in the meninges of TNFR1−/− and TNFR1-IL-6−/− mice in contrast to IL-6−/− and wild type mice. Furthermore, the increased mortality of TNFR1−/− and TNFR1-IL-6−/− mice correlated with decreased glial cell activation compared to IL-6−/− or wild type mice after pneumococcal meningitis. Altogether, the results show the importance of TNFR1 and IL-6 in the regulation of the innate immune response. The lack of TNFR1 and IL-6 results in higher mortality by weakened immune defence, whereas the lack of TNFR1 results in more severe impairment of the innate immune response than the lack of IL-6 alone.

  6. Effect of feed restriction and initial body weight on growth performance, body composition, and hormones in male pigs immunized against gonadotropin-releasing factor.

    Science.gov (United States)

    Moore, K L; Mullan, B P; Kim, J C; Payne, H G; Dunshea, F R

    2016-09-01

    Pigs immunized against gonadotropin-releasing factor (GnRF) have increased carcass fatness compared to entire males; however, the timing of this increase in fatness after the second immunization against GnRF has not been determined. An experiment was conducted to identify and compare the growth performance, body composition, and physiological changes in immunocastrated males (IC males) at different BW and feeding levels. A total of 64 pigs were used in a 2 × 2 × 2 factorial experiment with the treatments being 1) sex (entire males or IC males), 2) initial BW (45.9 kg [light] or 78.3 kg [heavy]), and 3) feeding regime (2.5 times maintenance [restricted] or ad libitum). The pigs were individually housed, and the diets were fed for 4 wk after the second immunization against GnRF until slaughter at either 68.4 kg BW (light) or 105.8 kg BW (heavy). Immunocastrated males on a restricted feed intake had a lower ADG compared to entire males from d 15 to 28 and d 0 to 28 ( 0.011 and 0.011, respectively). Fat deposition was not affected by sex from d 0 to 14, but from d 15 to 28 IC males deposited 45 g/d more fat than entire males ( = 0.025). Immunocastrated male pigs fed ad libitum deposited 87 g/d more fat from d 15 to 28 than entire males fed ad libitum ( = 0.036). However, there was no difference in fat deposition between IC males and entire males when feed intake was restricted from d 15 to 28. Plasma urea nitrogen levels were greater in IC males compared to entire males from d 7 after the second immunization against GnRF ( 0.05 for d 7, 10, 14, 21, and 28). Plasma concentrations of IGF-1 were lower for IC males compared to entire males on d 3, 7, 10, and 28 ( 0.05 for all days). The following conclusions were made: 1) when pigs are immunized at a light BW (50 kg) and/or are on a restricted feed intake, they have a reduced propensity to deposit fat; however, the restriction in feed intake adversely affects growth rate. 2) The majority of fat deposition for males

  7. The in vivo role of stem cell factor (c-kit ligand) on mastocytosis and host protective immunity to the intestinal nematode Trichinella spiralis in mice.

    Science.gov (United States)

    Grencis, R K; Else, K J; Huntley, J F; Nishikawa, S I

    1993-01-01

    The role of stem cell factor (SCF) in the generation of intestinal mast cell hyperplasia and host protective immunity following helminth infection was investigated using the Trichinella spiralis/mouse model. In vivo administration of a monoclonal antibody specific for the receptor for SCF (c-kit) was found to completely prevent the generation of intestinal mastocytosis normally observed following T. spiralis infection. This was reflected by markedly reduced intestinal mast cell protease (IMCP) levels in both tissue and serum. Moreover, animals treated with anti-c-kit antibody failed to show any evidence of worm expulsion from the gut. The data demonstrate for the first time, a critical role for the SCF in the generation of mucosal mastocytosis and host protective immunity following an intestinal helminth infection.

  8. Effect of heat stress during late gestation on immune function and growth performance of calves: isolation of altered colostral and calf factors.

    Science.gov (United States)

    Monteiro, A P A; Tao, S; Thompson, I M; Dahl, G E

    2014-10-01

    Calves born to cows exposed to heat stress during the dry period and fed their dams' colostrum have compromised passive and cell-mediated immunity compared with calves born to cows cooled during heat stress. However, it is unknown if this compromised immune response is caused by calf or colostrum intrinsic factors. Two studies were designed to elucidate the effects of colostrum from those innate to the calf. The objective of the first study was to evaluate the effect of maternal heat stress during the dry period on calf-specific factors related to immune response and growth performance. Cows were dried off 46 d before expected calving and randomly assigned to 1 of 2 treatments: heat stress (HT; n=18) or cooling (CL; n=18). Cows of the CL group were housed with sprinklers, fans and shade, whereas cows of HT group had only shade. After calving, the cows were milked and their colostrum was frozen for the subsequent study. Colostrum from cows exposed to a thermoneutral environment during the dry period was pooled and stored frozen (-20 °C). Within 4h of birth, 3.8L of the pooled colostrum from thermoneutral cows was fed to calves born to both HT and CL cows. Day of birth was considered study d 0. All calves were exposed to the same management and weaned at d 49. Blood samples were collected before colostrum feeding, 24h after birth and twice weekly up to d 28. Total serum IgG concentrations were determined. Body weight was recorded at birth and at d 15, 30, 45, and 60. Relative to CL calves, HT calves were lighter at birth (38.3 vs. 43.1 kg), but no difference in weight gain was observed at d 60. Additionally, HT calves had lower apparent efficiency of IgG absorption (26.0 vs. 30.2%), but no differences were observed for total IgG concentration. The objective of the second study was to evaluate the isolated effect of the colostrum from HT cows on calf immune response and growth performance. The experimental design was identical to the first study, but all calves were

  9. Multiplex-PCR-Based Screening and Computational Modeling of Virulence Factors and T-Cell Mediated Immunity in Helicobacter pylori Infections for Accurate Clinical Diagnosis.

    Directory of Open Access Journals (Sweden)

    Sinem Oktem-Okullu

    Full Text Available The outcome of H. pylori infection is closely related with bacteria's virulence factors and host immune response. The association between T cells and H. pylori infection has been identified, but the effects of the nine major H. pylori specific virulence factors; cagA, vacA, oipA, babA, hpaA, napA, dupA, ureA, ureB on T cell response in H. pylori infected patients have not been fully elucidated. We developed a multiplex- PCR assay to detect nine H. pylori virulence genes with in a three PCR reactions. Also, the expression levels of Th1, Th17 and Treg cell specific cytokines and transcription factors were detected by using qRT-PCR assays. Furthermore, a novel expert derived model is developed to identify set of factors and rules that can distinguish the ulcer patients from gastritis patients. Within all virulence factors that we tested, we identified a correlation between the presence of napA virulence gene and ulcer disease as a first data. Additionally, a positive correlation between the H. pylori dupA virulence factor and IFN-γ, and H. pylori babA virulence factor and IL-17 was detected in gastritis and ulcer patients respectively. By using computer-based models, clinical outcomes of a patients infected with H. pylori can be predicted by screening the patient's H. pylori vacA m1/m2, ureA and cagA status and IFN-γ (Th1, IL-17 (Th17, and FOXP3 (Treg expression levels. Herein, we report, for the first time, the relationship between H. pylori virulence factors and host immune responses for diagnostic prediction of gastric diseases using computer-based models.

  10. Multiplex-PCR-Based Screening and Computational Modeling of Virulence Factors and T-Cell Mediated Immunity in Helicobacter pylori Infections for Accurate Clinical Diagnosis

    Science.gov (United States)

    Oktem-Okullu, Sinem; Tiftikci, Arzu; Saruc, Murat; Cicek, Bahattin; Vardareli, Eser; Tozun, Nurdan; Kocagoz, Tanil; Sezerman, Ugur; Yavuz, Ahmet Sinan; Sayi-Yazgan, Ayca

    2015-01-01

    The outcome of H. pylori infection is closely related with bacteria's virulence factors and host immune response. The association between T cells and H. pylori infection has been identified, but the effects of the nine major H. pylori specific virulence factors; cagA, vacA, oipA, babA, hpaA, napA, dupA, ureA, ureB on T cell response in H. pylori infected patients have not been fully elucidated. We developed a multiplex- PCR assay to detect nine H. pylori virulence genes with in a three PCR reactions. Also, the expression levels of Th1, Th17 and Treg cell specific cytokines and transcription factors were detected by using qRT-PCR assays. Furthermore, a novel expert derived model is developed to identify set of factors and rules that can distinguish the ulcer patients from gastritis patients. Within all virulence factors that we tested, we identified a correlation between the presence of napA virulence gene and ulcer disease as a first data. Additionally, a positive correlation between the H. pylori dupA virulence factor and IFN-γ, and H. pylori babA virulence factor and IL-17 was detected in gastritis and ulcer patients respectively. By using computer-based models, clinical outcomes of a patients infected with H. pylori can be predicted by screening the patient's H. pylori vacA m1/m2, ureA and cagA status and IFN-γ (Th1), IL-17 (Th17), and FOXP3 (Treg) expression levels. Herein, we report, for the first time, the relationship between H. pylori virulence factors and host immune responses for diagnostic prediction of gastric diseases using computer—based models. PMID:26287606

  11. The role of the Th1 transcription factor T-bet in a mouse model of immune-mediated bone-marrow failure.

    Science.gov (United States)

    Tang, Yong; Desierto, Marie J; Chen, Jichun; Young, Neal S

    2010-01-21

    The transcription factor T-bet is a key regulator of type 1 immune responses. We examined the role of T-bet in an animal model of immune-mediated bone marrow (BM) failure using mice carrying a germline T-bet gene deletion (T-bet(-/-)). In comparison with normal C57BL6 (B6) control mice, T-bet(-/-) mice had normal cellular composition in lymphohematopoietic tissues, but T-bet(-/-) lymphocytes were functionally defective. Infusion of 5 x 10(6) T-bet(-/-) lymph node (LN) cells into sublethally irradiated, major histocompatibility complex-mismatched CByB6F1 (F1) recipients failed to induce the severe marrow hypoplasia and fatal pancytopenia that is produced by injection of similar numbers of B6 LN cells. Increasing T-bet(-/-) LN-cell dose to 10 to 23 x 10(6) per recipient led to only mild hematopoietic deficiency. Recipients of T-bet(-/-) LN cells had no expansion in T cells or interferon-gamma-producing T cells but showed a significant increase in Lin(-)Sca1(+)CD117(+)CD34(-) BM cells. Plasma transforming growth factor-beta and interleukin-17 concentrations were increased in T-bet(-/-) LN-cell recipients, possibly a compensatory up-regulation of the Th17 immune response. Continuous infusion of interferon-gamma resulted in hematopoietic suppression but did not cause T-bet(-/-) LN-cell expansion or BM destruction. Our data provided fresh evidence demonstrating a critical role of T-bet in immune-mediated BM failure.

  12. Human pathogenic Borrelia spielmanii sp nov resists complement-mediated killing by direct binding of immune regulators factor H and factor H-like protein 1

    NARCIS (Netherlands)

    Herzberger, Pia; Siegel, Corinna; Skerka, Christine; Fingerle, Volker; Schulte-Spechtel, Ulrike; van Dam, Alje; Wilske, Bettina; Brade, Volker; Zipfel, Peter F.; Wallich, Reinhard; Kraiczy, Peter

    2007-01-01

    Borrelia spielmanii sp. nov. has recently been shown to be a novel human pathogenic genospecies that causes Lyme disease in Europe. In order to elucidate the immune evasion mechanisms of B. spielmanii, we compared the abilities of isolates obtained from Lyme disease patients and tick isolate PC-Eq17

  13. The structure of pyogenecin immunity protein, a novel bacteriocin-like immunity protein from streptococcus pyogenes.

    Energy Technology Data Exchange (ETDEWEB)

    Chang, C.; Coggill, P.; Bateman, A.; Finn, R.; Cymborowski, M.; Otwinowski, Z.; Minor, W.; Volkart, L.; Joachimiak, A.; Wellcome Trust Sanger Inst.; Univ. of Virginia; UT Southwestern Medical Center

    2009-12-17

    Many Gram-positive lactic acid bacteria (LAB) produce anti-bacterial peptides and small proteins called bacteriocins, which enable them to compete against other bacteria in the environment. These peptides fall structurally into three different classes, I, II, III, with class IIa being pediocin-like single entities and class IIb being two-peptide bacteriocins. Self-protective cognate immunity proteins are usually co-transcribed with these toxins. Several examples of cognates for IIa have already been solved structurally. Streptococcus pyogenes, closely related to LAB, is one of the most common human pathogens, so knowledge of how it competes against other LAB species is likely to prove invaluable. We have solved the crystal structure of the gene-product of locus Spy-2152 from S. pyogenes, (PDB: 2fu2), and found it to comprise an anti-parallel four-helix bundle that is structurally similar to other bacteriocin immunity proteins. Sequence analyses indicate this protein to be a possible immunity protein protective against class IIa or IIb bacteriocins. However, given that S. pyogenes appears to lack any IIa pediocin-like proteins but does possess class IIb bacteriocins, we suggest this protein confers immunity to IIb-like peptides. Combined structural, genomic and proteomic analyses have allowed the identification and in silico characterization of a new putative immunity protein from S. pyogenes, possibly the first structure of an immunity protein protective against potential class IIb two-peptide bacteriocins. We have named the two pairs of putative bacteriocins found in S. pyogenes pyogenecin 1, 2, 3 and 4.

  14. The structure of pyogenecin immunity protein, a novel bacteriocin-like immunity protein from Streptococcus pyogenes

    Directory of Open Access Journals (Sweden)

    Volkart Lour

    2009-12-01

    Full Text Available Abstract Background Many Gram-positive lactic acid bacteria (LAB produce anti-bacterial peptides and small proteins called bacteriocins, which enable them to compete against other bacteria in the environment. These peptides fall structurally into three different classes, I, II, III, with class IIa being pediocin-like single entities and class IIb being two-peptide bacteriocins. Self-protective cognate immunity proteins are usually co-transcribed with these toxins. Several examples of cognates for IIa have already been solved structurally. Streptococcus pyogenes, closely related to LAB, is one of the most common human pathogens, so knowledge of how it competes against other LAB species is likely to prove invaluable. Results We have solved the crystal structure of the gene-product of locus Spy_2152 from S. pyogenes, (PDB:2fu2, and found it to comprise an anti-parallel four-helix bundle that is structurally similar to other bacteriocin immunity proteins. Sequence analyses indicate this protein to be a possible immunity protein protective against class IIa or IIb bacteriocins. However, given that S. pyogenes appears to lack any IIa pediocin-like proteins but does possess class IIb bacteriocins, we suggest this protein confers immunity to IIb-like peptides. Conclusions Combined structural, genomic and proteomic analyses have allowed the identification and in silico characterization of a new putative immunity protein from S. pyogenes, possibly the first structure of an immunity protein protective against potential class IIb two-peptide bacteriocins. We have named the two pairs of putative bacteriocins found in S. pyogenes pyogenecin 1, 2, 3 and 4.

  15. Immunobiotic Lactobacillus jensenii as immune-health promoting factor to improve growth performance and productivity in post-weaning pigs

    OpenAIRE

    Suda, Yoshihito; Villena, Julio Cesar; Takahashi, Yu; Hosoya, Shoichi; Tomosada, Yohsuke; Tsukida, Kohichiro; Shimazu, Tomoyuki; Aso, Hisashi; Tohno, Masanori; Ishida, Mitsuharu; Makino, Seiya; Ikegami, Shuji; Kitazawa, Haruki

    2015-01-01

    Background: Immunoregulatory probiotics (immunobiotics) have been proposed to improve piglets? immune system to avoid intestinal infections and reduce unproductive inflammation after weaning. Previously, it was demonstrated that Lactobacillus jensenii TL2937 (LjTL2937) attenuated the inflammatory response triggered by activation of Toll-like receptor 4 (TLR-4) in porcine intestinal epithelial (PIE) cells and antigen presenting cells (APCs) from porcine Peyer?s patches (PP). Objectiv...

  16. High mobility group box 1 protein (HMGB1) as an immune-modulating factor for polarization of human T lymphocytes

    Institute of Scientific and Technical Information of China (English)

    Lifeng Huang; Yongming Yao; Haidong Meng; Xiaodong Zhao; Ning Dong; Yan Yu

    2008-01-01

    Objective This study was performed to investigate the effect of high mobility group box-1 protein (HMGB 1) on immune function of human T lymphocytes in vitro and explore its potential role in cell-mediated immune dysfunction.Methods Fresh blood was obtained from healthy adult volunteers and peripheral blood mononuclear cells (PBMCs) were isolated,then rhHMGB 1 was added to PBMCs.Four-color flow cytometric (FCM) analysis was used for the measurement of intracellular cytokine including interleukin Results (1) Different stimulating time and dosage of rhHMGB 1 did not alter the number of IFN-a positive cells (Th 1).rhHMGB 1 stimulation provoked a dose-dependent and time-dependent increase in Th2 subset and decrease in ratio of Th 1 to Th2.(2) Compared with the untreated cells,when the cells were coincubated with rhHMGB 1 (10-100ng/ml) for 12 hrs,protein release of IL-2 and sIL-2R were significantly up-regulated.At 48 hrs,in contrast,protein production was relatively lower in cells after exposure to 100-1000 ng/ml rhHMGBI.Conclusions These findings demonstrated that HMGB1 has a dual influence on immune functions of human T lymphocytes.

  17. Prevalence of immunity presumed using rabies vaccination history and household factors associated with vaccination status among domestic dogs in Japan.

    Science.gov (United States)

    Hidano, Arata; Hayama, Yoko; Tsutsui, Toshiyuki

    2012-01-01

    Rabies was eliminated in Japan over 50 years ago; however, the recent increase in the movement of humans and animals across the world highlights the potential threat of disease reentry into the country. The immune status against rabies among the dog population in Japan is not well known; thus, the purpose of this study was to estimate the prevalence of dogs with effective immunity from the vaccination history using a web-based survey. We found that 76.9% (95% confidence interval, 75.8-78.1) of dogs in this study population belonged to the population in which 90% were assumed to have the internationally accepted antibody titer. We showed that dogs taken less frequently for walks were less likely to be vaccinated. Additionally, the frequency of encounters with other dogs during walks and the number of individuals in households were associated with vaccination history. To our knowledge, this study is the first report estimating the prevalence of dogs in Japan with effective immunity against rabies. Further, we identified the population with low vaccination coverage as well as the heterogeneous characteristics of vaccination history among the dog population. These findings contribute to the implementation of an efficient strategy for improving the overall vaccination coverage in Japan and the development of a quantitative risk assessment of rabies.

  18. Inflammatory bowel disease related innate immunity and adaptive immunity

    Science.gov (United States)

    Huang, Yuan; Chen, Zhonge

    2016-01-01

    Inflammatory bowel disease (IBD) is a chronic nonspecific intestinal inflammatory disease, including ulcerative colitis (UC) and Crohn’s disease (CD). Its pathogenesis remains not yet clear. Current researchers believe that after environmental factors act on individuals with genetic susceptibility, an abnormal intestinal immune response is launched under stimulation of intestinal flora. However, previous studies only focused on adaptive immunity in the pathogenesis of IBD. Currently, roles of innate immune response in the pathogenesis of intestinal inflammation have also drawn much attention. In this study, IBD related innate immunity and adaptive immunity were explained, especially the immune mechanisms in the pathogenesis of IBD. PMID:27398134

  19. Tingkat dan Faktor Risiko Kekebalan Protektif terhadap Rabies pada Anjing di Kota Makassar (RATE AND RISK FACTORS OF PROTECTIVE IMMUNITY AGAINST RABIES ON DOGS IN THE CITY OF MAKASSAR

    Directory of Open Access Journals (Sweden)

    Sri Utami

    2014-04-01

    Full Text Available The rate and risk factors on protective immunity against rabies were conducted in Makassar city. Theaims of this study were to determine the level of immunity of dog and find out the association betweenmanagement factors and the level of maintenance of the dog immunity against rabies. Two hundred andforty-six serum samples were collected for measurement of dog immunity level with a method of enzymelinked immunosorbent assay (ELISA. Maintenance management data were gathered throughquestionnaires and direct observation. Analysis of data obtained by the level of immunity was donedescriptively. The significance association between the risk factors and the strength of immunity level wascalculated by using Chi square (X2 and odds ratios. The results showed only 12.2% of dogs had a protectiveantibody against rabies at > 0.5 IU/ml. Factors affecting the level of protective immunity against rabieswere the first vaccination at 1-6 months age (OR = 18.6, post-vaccination after 1-6 months (OR = 6.0, themaintenance location of dogs in urban areas (OR = 4.5, dog caring management in house (OR = 3.8, andowner income above Rp. 2.000.000/month (OR = 3.0. It is concluded that the low level of protective immunityagainst rabies and the dog bites reported each year indicates that Makassar, as endemic areal of rabies,is a threat to the outbreak of the disease in animals and humans to the surrounding areas.

  20. Brucella ovis: invasion, traffic, virulence factors and immune responseBrucella ovis: invasão, tráfego, fatores de virulência e resposta imune

    Directory of Open Access Journals (Sweden)

    João Marcelo Azevedo de Paula Antunes

    2013-06-01

    Full Text Available Brucellosis remains an economic problem in animals and public health. Worldwide ovine brucellosis caused by Brucella ovis is considered a major cause of infertility in sheep. The factors responsible for persistence of the agent in these locations are not known, as well as the mechanisms involved in immune defense and possibly the persistence of the agent. Brucella spp. induces moderate inflammatory response. The nature of the intracellular agent stimulates immune response of the type 1 helper T lymphocytes. Studies of the pathogenesis of ovine brucellosis are scarce. Recent developments have shown that the inflammatory response induced by moderate brucelas represent probably the result of an attempt to escape the immune response and suppression of host immune response. Were reviewed by the mechanisms described by brucelas and Brucella ovis for penetration into the host, escape of the immune response and the immune response generated by the infection. A brucelose permanece como problema econômico em animais e de saúde pública. Em todo o mundo a brucelose ovina ocasionada pela Brucella ovis é considerada uma das principais causas de infertilidade em ovinos. Os fatores responsáveis pela persistência do agente nestes locais não são conhecidos, bem como os mecanismos imunes envolvidos na defesa e eventualmente na persistência do agente. Brucella spp. induz resposta inflamatória moderada. A natureza intracelular do agente estimula resposta imune celular do tipo linfócito T helper 1. Os estudos de patogenia da brucelose ovina são escassos. Recentes avanços demonstraram que a resposta inflamatória moderada induzida pelas brucelas representam provavelmente o resultado de tentativa de escape da resposta imune e supressão da resposta imune hospedeira. Foram revisados os mecanismos descritos pelas brucelas e pela Brucella ovis para penetração no hospedeiro, escape da resposta imune, bem como a resposta imunológica gerada pela infecção.

  1. High-altitude hypoxia induces disorders of the brain-endocrine-immune network through activation of corticotropin-releasing factor and its type-1 receptors

    Institute of Scientific and Technical Information of China (English)

    Xue-qun CHEN; Fan-ping KONG; Yang ZHAO; Ji-zeng DU

    2012-01-01

    High-altitude hypoxia can induce physiological dysfunction and mountain sickness,but the underlying mechanism is not fully understood.Corticotrophin-releasing factor (CRF) and CRF type-1 receptors (CRFR1) are members of the CRF family and the essential controllers of the physiological activity of the hypothalamo-pituitary-adrenal (HPA) axis and modulators of endocrine and behavioral activity in response to various stressors.We have previously found that high-altitude hypoxia induces disorders of the brain-endocrine-immune network through activation of CRF and CRFR1 in the brain and periphery that include activation of the HPA axis in a time-and dose-dependent manner,impaired or improved learning and memory,and anxiety-like behavioral change.Meanwhile,hypoxia induces dysfunctions of the hypothalamo-pituitary-endocrine and immune systems,including suppression of growth and development,as well as inhibition of reproductive,metabolic and immune functions.In contrast,the small mammals that live on the Qinghai-Tibet Plateau alpine meadow display low responsiveness to extreme high-altitudehypoxia challenge,suggesting well-acclimatized genes and a physiological strategy that developed during evolution through interact-ions between the genes and environment.All the findings provide evidence for understanding the neuroendocrine mechanisms of hypoxia-induced physiological dysfunction.This review extends these findings.

  2. MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective Antigen

    Directory of Open Access Journals (Sweden)

    Judith A. James

    2012-12-01

    Full Text Available Anthrax Lethal Toxin consists of Protective Antigen (PA and Lethal Factor (LF, and current vaccination strategies focus on eliciting antibodies to PA. In human vaccination, the response to PA can vary greatly, and the response is often directed toward non-neutralizing epitopes. Variable vaccine responses have been shown to be due in part to genetic differences in individuals, with both MHC class II and other genes playing roles. Here, we investigated the relative contribution of MHC class II versus non-MHC class II genes in the humoral response to PA and LF immunization using three immunized strains of inbred mice: A/J (H-2k at the MHC class II locus, B6 (H-2b, and B6.H2k (H-2k. IgG antibody titers to LF were controlled primarily by the MHC class II locus, whereas IgG titers to PA were strongly influenced by the non-MHC class II genetic background. Conversely, the humoral fine specificity of reactivity to LF appeared to be controlled primarily through non-MHC class II genes, while the specificity of reactivity to PA was more dependent on MHC class II. Common epitopes, reactive in all strains, occurred in both LF and PA responses. These results demonstrate that MHC class II differentially influences humoral immune responses to LF and PA.

  3. The streptomycin mouse model for Salmonella diarrhea: functional analysis of the microbiota, the pathogen's virulence factors, and the host's mucosal immune response.

    Science.gov (United States)

    Kaiser, Patrick; Diard, Médéric; Stecher, Bärbel; Hardt, Wolf-Dietrich

    2012-01-01

    The mammalian intestine is colonized by a dense microbial community, the microbiota. Homeostatic and symbiotic interactions facilitate the peaceful co-existence between the microbiota and the host, and inhibit colonization by most incoming pathogens ('colonization resistance'). However, if pathogenic intruders overcome colonization resistance, a fierce, innate inflammatory defense can be mounted within hours, the adaptive arm of the immune system is initiated, and the pathogen is fought back. The molecular nature of the homeostatic interactions, the pathogen's ability to overcome colonization resistance, and the triggering of native and adaptive mucosal immune responses are still poorly understood. To study these mechanisms, the streptomycin mouse model for Salmonella diarrhea is of great value. Here, we review how S. Typhimurium triggers mucosal immune responses by active (virulence factor elicited) and passive (MyD88-dependent) mechanisms and introduce the S. Typhimurium mutants available for focusing on either response. Interestingly, mucosal defense turns out to be a double-edged sword, limiting pathogen burdens in the gut tissue but enhancing pathogen growth in the gut lumen. This model allows not only studying the molecular pathogenesis of Salmonella diarrhea but also is ideally suited for analyzing innate defenses, microbe handling by mucosal phagocytes, adaptive secretory immunoglobulin A responses, probing microbiota function, and homeostatic microbiota-host interactions. Finally, we discuss the general need for defined assay conditions when using animal models for enteric infections and the central importance of littermate controls.

  4. Windows Into an Open-System Magma Chamber: Cognate Xenoliths From the Kameni Islands, Santorini, Greece

    Science.gov (United States)

    Martin, V. M.; Holness, M. B.; Pyle, D. M.

    2003-12-01

    The composition of the dacite forming the Kameni Islands has been remarkably uniform over the last 2200 years, attesting to significant replenishment and mixing in the shallow open-system chamber. Insights into chamber evolution can be gained from the abundant cognate xenoliths in the dacite. The xenoliths include both cumulates from the chamber floor and quenched fragments of replenishing magma. They fall into 7 groups distinguishable by differences in chemistry, texture and mechanical behaviour. Quench xenoliths with linear CSDs are thought to have formed on the injection of aphyric magma into the chamber. Since these xenoliths commonly have an andesitic composition, this suggests the expulsion of an aphyric melt from a crystal mush in a lower chamber by filter-pressing during compaction. Those with strongly bi-modal grain size distributions indicate injection of phenocryst-bearing replenishing magma. Quench xenoliths with evolved compositions are typically found as large isolated blocks randomly dispersed throughout the host lava. In contrast, the more mafic xenoliths are distributed in tight, elongate, clusters aligned in the direction of flow, and comprising up to 100 individuals. The contrasting spatial distributions of the xenoliths reflects the different rheological properties of the xenolith types, with implications for the ease of mixing and assimilation of batches of replenishing melt in the magma chamber. The rare cumulate xenoliths are small, and are characterised by coarse grain-size, low glass and vesicle content, and are predominantly found in lava from the last (1950) eruption. They are generally found enveloped by less dense and highly vesicular quench-type xenoliths, which probably provided the buoyancy forces necessary for entrainment. Mapping of the xenolith types shows that each flow forming the Kameni Islands has a distinct xenolith population, reflecting the changing state of the emptying magma chamber. Seismic activity has preceded most

  5. Interaction between thymidylate synthase and its cognate mRNA in zebrafish embryos.

    Directory of Open Access Journals (Sweden)

    Yuyan Zhang

    Full Text Available Thymidylate synthase (TS, which catalyzes the de novo synthesis of dUMP, is an important target for cancer therapy. In this report, the effects of 5-fluorouracil (5-FU and ZD1694 on the regulation of TS gene expression were evaluated in zebrafish embryos. Our results revealed that the expression of TS was increased by about six-fold when embryos were treated with 1.0 microM 5-FU and there was a greater than 10-fold increase in the TS protein level after treatment with 0.4 microM ZD1694. Northern blot analysis confirmed that expression of TS mRNA was identical in treated or untreated embryos. Gel shift and immunoprecipitation assays revealed that zebrafish TS was specifically bound with its cognate mRNA in vitro and in vivo. We identified a 20 nt RNA sequence, TS:N20, localized to the 5'-UTR of TS mRNA, which corresponded to nt 13-32; TS:N20 bound to the TS protein with an affinity similar to that of the full-length TS mRNA. The MFold program predicted that TS:N20 formed a stable stem-loop structure similar to that of the cis-acting element found in human TS mRNA. Variant RNAs with either a deletion or mutation in the core motif of TS:N20 were unable to bind to the TS protein. In vitro translation experiments, using the rabbit lysate system, confirmed that zebrafish TS mRNA translation was significantly repressed when an excess amount of TS protein was included in the system. Additionally, a TS stability experiment confirmed that treatment of zebrafish embryos with 5-FU could increase the TS stability significantly, and the half life of TS protein was about 2.7 times longer than in untreated embryos. Our study revealed a structural requirement for the interaction of TS RNA with TS protein. These findings also demonstrated that the increase in TS protein induced by 5-FU occurs at the post-transcriptional level and that increased stability and translation efficiency both contributed to the increase in TS protein levels induced by TS inhibitors.

  6. Gallus Heat shock cognate protein 70, a novel binding partner of Apoptin

    Directory of Open Access Journals (Sweden)

    Chen Kun

    2011-06-01

    Full Text Available Abstract Background Chicken anemia virus (CAV infection of newly hatched chickens induces generalized lymphoid atrophy and causes immunosuppressive. VP3, also known as Apoptin, is non-structural protein of CAV. Apoptin specifically induces apoptosis in transformed or tumor cells but not in normal cells. In particular, there are no known cellular homologues of Apoptin hindering genetic approaches to elucidate its cellular function. Although a number of Apoptin-interacting molecules have been identified, the molecular mechanism underlying Apoptin's action is still poorly understood. To learn more about the molecular mechanism of Apoptin's action, we searched for Apoptin associated proteins. Results Using yeast two-hybrid and colony-life filter approaches we got five positive yeast clones. Through sequencing and BLASTed against NCBI, one of the clones was confirmed containing Gallus heat shock cognate protein 70 (Hsc70. Hsc70 gene was clone into pRK5-Flag plasmid, coimmunoprecipitation assay show both exogenous Hsc70 and endogenous Hsc70 can interact with Apoptin. Truncated Apoptin expression plasmids were made and coimmunoprecipitation were performed, the results show the binding domain of Apoptin with Hsc70 is located between amino acids 30-60. Truncated expression plasmids of Hsc70 were also constructed and coimmunoprecipitation were performed, the results show the peptide-binding and variable domains of Hsc70 are responsible for the binding to Apoptin. Confocal assays were performed and results show that under physiological condition Hsc70 is predominantly distributed in cytoplasm, whereas Hsc70 is translocated into the nuclei and colocalized with Apoptin in the presence of Apoptin in DF-1 cell. Functional studies show that Apoptin markedly down-regulate the mRNA level of RelA/p65 in DF-1 cell. To explore the effect of Hsc70 on Apoptin-mediated RelA/p65 gene expression, we have searched two Hsc70 RNAi sequences, and found that all of them

  7. LA PROTEÍNA DE ESTRÉS, HEAT SHOCK COGNATE (HSC70 SE SOBREEXPRESA EN OSTEOBLASTOS SOMETIDOS A CENTRIFUGACIÓN OVEREXPRESESSION HEAT SHOCK COGNATE (HSC70 PROTEIN IN OSTEOBLASTS SUBMITED TO CENTRIFUGAL FORCES

    Directory of Open Access Journals (Sweden)

    Carlos A Guerrero F

    2006-07-01

    Full Text Available Antecedentes. El osteoblasto tiene la capacidad de estimular la neoformación del tejido óseo, mediante la síntesis de proteínas tales como las proteínas morfogenéticas, factores de crecimiento y proteínas colágenas y no colágenas. A su vez, indirectamente controla los procesos de reabsorción sintetizando otra serie de proteínas estimuladoras de la actividad osteoclastogénica. Objetivo. El propósito de este trabajo de investigación fue analizar la expresión de la proteína de choque térmico HSC70 en un cultivo primario de osteoblastos, después de someterlo a una fuerza tensil mediante centrifugación, determinando el patrón de proteínas mediante análisis electroforético. Material y métodos. A partir de cráneos de ratones lactantes ICR se obtuvieron cultivos de células con características morfológicas tipo fibroblastoide, con prolongaciones alargadas y citoplasmas ligeramente cuboidales que sugiere un cultivo enriquecido de osteoblastos; los cuales fueron sometidos a centrifugación y se analizó por inmunocitoquímica, electroforesis y Western blot la expresión diferencial de la proteína HSC70. Resultados.La técnica de electroforesis SDS-PAGE unidimensional no permitió determinar diferencias en el patrón de corrido entre osteoblastos tratados respecto a los no tratados con la fuerza tensil. Sin embargo, la proteína HSC70 se sobre-expresa en osteoblastos sometidos a centrifugación analizada mediante la técnica de Western blot e inmuno­histoquímica. Conclusión.Aunque la electroforesis no determinó diferencias en el patrón de corrido, la proteína de estrés HSC70 se sobre-expresó en osteoblastos sometidos a centrifugación analizada mediante la técnica de Western blot e inmunocitoquímica, sugiriendo que es importante en este tipo de estrés.Background. Osteoblasts can stimulate new bone formation by protein synthesis, such as, bone morphogenetic proteins, growth factors and collagen and non

  8. Insect neuropeptide bursicon homodimers induce innate immune and stress genes during molting by activating the NF-κB transcription factor Relish.

    Directory of Open Access Journals (Sweden)

    Shiheng An

    Full Text Available BACKGROUND: Bursicon is a heterodimer neuropeptide composed of two cystine knot proteins, bursicon α (burs α and bursicon β (burs β, that elicits cuticle tanning (melanization and sclerotization through the Drosophila leucine-rich repeats-containing G protein-coupled receptor 2 (DLGR2. Recent studies show that both bursicon subunits also form homodimers. However, biological functions of the homodimers have remained unknown until now. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we show in Drosophila melanogaster that both bursicon homodimers induced expression of genes encoding antimicrobial peptides (AMPs in neck-ligated adults following recombinant homodimer injection and in larvae fat body after incubation with recombinant homodimers. These AMP genes were also up-regulated in 24 h old unligated flies (when the endogenous bursicon level is low after injection of recombinant homodimers. Up-regulation of AMP genes by the homodimers was accompanied by reduced bacterial populations in fly assay preparations. The induction of AMP expression is via activation of the NF-κB transcription factor Relish in the immune deficiency (Imd pathway. The influence of bursicon homodimers on immune function does not appear to act through the heterodimer receptor DLGR2, i.e. novel receptors exist for the homodimers. CONCLUSIONS/SIGNIFICANCE: Our results reveal a mechanism of CNS-regulated prophylactic innate immunity during molting via induced expression of genes encoding AMPs and genes of the Turandot family. Turandot genes are also up-regulated by a broader range of extreme insults. From these data we infer that CNS-generated bursicon homodimers mediate innate prophylactic immunity to both stress and infection during the vulnerable molting cycle.

  9. Elafin, an elastase-specific inhibitor, is cleaved by its cognate enzyme neutrophil elastase in sputum from individuals with cystic fibrosis.

    LENUS (Irish Health Repository)

    Guyot, Nicolas

    2008-11-21

    Elafin is a neutrophil serine protease inhibitor expressed in lung and displaying anti-inflammatory and anti-bacterial properties. Previous studies demonstrated that some innate host defense molecules of the cystic fibrosis (CF) and chronic obstructive pulmonary disease airways are impaired due to increased proteolytic degradation observed during lung inflammation. In light of these findings, we thus focused on the status of elafin in CF lung. We showed in the present study that elafin is cleaved in sputum from individuals with CF. Pseudomonas aeruginosa-positive CF sputum, which was found to contain lower elafin levels and higher neutrophil elastase (NE) activity compared with P. aeruginosa-negative samples, was particularly effective in cleaving recombinant elafin. NE plays a pivotal role in the process as only NE inhibitors are able to inhibit elafin degradation. Further in vitro studies demonstrated that incubation of recombinant elafin with excess of NE leads to the rapid cleavage of the inhibitor. Two cleavage sites were identified at the N-terminal extremity of elafin (Val-5-Lys-6 and Val-9-Ser-10). Interestingly, purified fragments of the inhibitor (Lys-6-Gln-57 and Ser-10-Gln-57) were shown to still be active for inhibiting NE. However, NE in excess was shown to strongly diminish the ability of elafin to bind lipopolysaccharide (LPS) and its capacity to be immobilized by transglutamination. In conclusion, this study provides evidence that elafin is cleaved by its cognate enzyme NE present at excessive concentration in CF sputum and that P. aeruginosa infection promotes this effect. Such cleavage may have repercussions on the innate immune function of elafin.

  10. Immune response

    Science.gov (United States)

    ... and tetanus antitoxin are examples of passive immunization. BLOOD COMPONENTS The immune system includes certain types of white ... lymphocytes develop, they normally learn to tell the difference between your own body tissues and substances that ...

  11. Molecular Cloning and Identification of a Heat Shock Cognate Protein 70 Gene, Thhsc70, in Thellungiella halophila

    Institute of Scientific and Technical Information of China (English)

    ZHANGXia; GUOShan-Li; YINHai-Bo; XIONGDong-Jin; ZHANGHui; ZHAOYan-Xiu

    2004-01-01

    Heat shock cognate proteins 70 (hsp70s) act as molecular chaperones. Some hsp70s are also expressed in unstressed plants, known as hsc70. To gain further knowledge about the hsc70, the Thellungiella halophila hsc70 (Thhsc70) gene that encoded the cytosolic hsc70 in salt cress (T.halophila (C.A.Mey.) O.E.Schulz) was identified. In unstressed plants the expression of Thhsc70was shown to be tissue-specific. The Thhsc70 gene was induced by heat and cold stresses, but almost not by salt and drought stresses. Overexpression of Thhsc7Ocould increase thermctolerance and chilling tolerance in transgenic Arabidopsis plants.

  12. Connecting two-component regulatory systems by a protein that protects a response regulator from dephosphorylation by its cognate sensor

    OpenAIRE

    Kato, Akinori; Groisman, Eduardo A.

    2004-01-01

    A fundamental question in signal transduction is how an organism integrates multiple signals into a cellular response. Here we report the mechanism by which the Salmonella PmrA/PmrB two-component system responds to the signal controlling the PhoP/PhoQ two-component system. We establish that the PhoP-activated PmrD protein binds to the phosphorylated form of the response regulator PmrA, preventing both its intrinsic dephosphorylation and that promoted by its cognate sensor kinase PmrB. This re...

  13. On the heart, the mind, and how inflammation killed the Cartesian dualism. Commentary on the 2015 Named Series: Psychological Risk Factors and Immune System Involvement in Cardiovascular Disease.

    Science.gov (United States)

    Mondelli, Valeria; Pariante, Carmine M

    2015-11-01

    The 2015 Named Series on "Psychological Risk Factors and Immune System Involvement in Cardiovascular Disease" was conceived with the idea of drawing attention to the interdisciplinary work aimed at investigating the relationships between the heart, metabolic system, brain, and mental health. In this commentary, we provide a brief overview of the manuscripts included in this Named Series and highlight how a better understanding of immune regulation will help us to move forward from the current "dualistic" perspective of the heart as separate from the mind to a more comprehensive understanding of the physiological links between cardiovascular and mental disorders. The manuscripts included in this Named Series range across a wide spectrum of topics, from understanding biological mechanisms explaining comorbidity between cardiovascular disease and psychiatric disorders to new insights into the dysregulation of inflammation associated with cardiovascular risk factors. Clearly, inflammation emerges as a cross-cutting theme across all studies. Data presented in this Series contribute to putting an end to an era in which the heart and the mind were considered to be separate entities in which the responses of one system did not affect the other.

  14. Interferon regulatory factor-1 (IRF-1) shapes both innate and CD8(+) T cell immune responses against West Nile virus infection.

    Science.gov (United States)

    Brien, James D; Daffis, Stephane; Lazear, Helen M; Cho, Hyelim; Suthar, Mehul S; Gale, Michael; Diamond, Michael S

    2011-09-01

    Interferon regulatory factor (IRF)-1 is an immunomodulatory transcription factor that functions downstream of pathogen recognition receptor signaling and has been implicated as a regulator of type I interferon (IFN)-αβ expression and the immune response to virus infections. However, this role for IRF-1 remains controversial because altered type I IFN responses have not been systemically observed in IRF-1(-/-) mice. To evaluate the relationship of IRF-1 and immune regulation, we assessed West Nile virus (WNV) infectivity and the host response in IRF-1(-/-) cells and mice. IRF-1(-/-) mice were highly vulnerable to WNV infection with enhanced viral replication in peripheral tissues and rapid dissemination into the central nervous system. Ex vivo analysis revealed a cell-type specific antiviral role as IRF-1(-/-) macrophages supported enhanced WNV replication but infection was unaltered in IRF-1(-/-) fibroblasts. IRF-1 also had an independent and paradoxical effect on CD8(+) T cell expansion. Although markedly fewer CD8(+) T cells were observed in naïve animals as described previously, remarkably, IRF-1(-/-) mice rapidly expanded their pool of WNV-specific cytolytic CD8(+) T cells. Adoptive transfer and in vitro proliferation experiments established both cell-intrinsic and cell-extrinsic effects of IRF-1 on the expansion of CD8(+) T cells. Thus, IRF-1 restricts WNV infection by modulating the expression of innate antiviral effector molecules while shaping the antigen-specific CD8(+) T cell response.

  15. [Immunization coverage and associated factors of women who have recently given birth in a city in São Paulo state].

    Science.gov (United States)

    Rocha, Bárbara Cristina Casemiro da; Carvalheira, Ana Paula Pinho; Ferrari, Anna Paula; Tonete, Vera Lúcia Pamplona; Duarte, Marli Teresinha Cassamassimo; Parada, Cristina Maria Garcia de Lima

    2016-06-01

    The importance of immunization among actions recommended in the prenatal period raises the possibility of protecting both the mother and the fetus against certain harmful diseases. The scope of this study was to assess the immunization coverage and associated factors of mothers whose deliveries occurred in the first half of 2012 in Botucatu, state of São Paulo. It is a cross-sectional study and data collection was performed in the two municipal maternity hospitals. Of the total births during the study period, 1318 mothers (90.3%) were included The data for the characterization of participants and their vaccination status (diphtheria, tetanus and hepatitis B) were obtained from the prenatal card, hospital records or interviews. For analysis of associated factors, the Chi-square test was used, with a 95% confidence interval and critical p of <0.05. Most of the study participants were 20 years old or more (84.4%), had seven years of schooling (69%), were monitored in prenatal care (99.2%) with seven or more appointments (88.9%). Miscarriage and infant death of 17.7% and 2.4% was recorded, respectively. Vaccination coverage was 68.4%. There was no association between sociodemographic and obstetric variables relating to prenatal care and vaccination of pregnant women.

  16. Innate Immunity Derived Factors as External Modulators of the CXCL12 - CXCR4 Axis and Their Role in Stem Cell Homing and Mobilization

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    Mariusz Z. Ratajczak, Karol Serwin, Gabriela Schneider

    2013-01-01

    Full Text Available The α-chemokine CXCL12 (stromal derived factor-1; SDF-1 and its corresponding GαI protein-coupled CXCR4 receptor axis play an important role in retention of hematopoietic stem progenitor cells (HSPCs in bone marrow (BM stem cell niches. CXCL12 has also been identified as a strong chemoattractant for HSPCs and implicated both in homing of HSPCs to BM after transplantation and in egress of these cells from BM into peripheral blood (PB. However, since CXCL12, as a peptide, is highly susceptible to degradation by proteolytic enzymes, its real biological availability in biological fluids may be somewhat limited. In this review, we will present data demonstrating that the CXCL12-CXCR4 axis is positively modulated by innate immunity-derived several external factors, ensuring that even low (near threshold doses of CXCL12 still exert a robust chemotactic influence on HSPCs.

  17. N-substituted benzyl matrinic acid derivatives inhibit hepatitis C virus (HCV replication through down-regulating host heat-stress cognate 70 (Hsc70 expression.

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    Na-Na Du

    Full Text Available Heat-stress cognate 70 (Hsc70 is a host factor that helps hepatitis C virus (HCV to complete its life cycle in infected hepatocytes. Using Hsc70 as a target for HCV inhibition, a series of novel N-substituted benzyl matrinic/sophoridinic acid derivatives was synthesized and evaluated for their anti-HCV activity in vitro. Among these analogues, compound 7c possessing N-p-methylbenzyl afforded an appealing ability to inhibit HCV replication with SI value over 53. Furthermore, it showed a good oral pharmacokinetic profile with area-under-curve (AUC of 13.4 µM·h, and a considerably good safety in oral administration in mice (LD50>1000 mg/kg. As 7c suppresses HCV replication via an action mode distinctly different from that of the marketed anti-HCV drugs, it has been selected as a new mechanism anti-HCV candidate for further investigation, with an advantage of no or decreased chance to induce drug-resistant mutations.

  18. Expression analyses of human cleft palate tissue suggest a role for osteopontin and immune related factors in palatal development

    DEFF Research Database (Denmark)

    Jakobsen, Linda P; Borup, Rehannah; Vestergaard, Janni

    2009-01-01

    Cleft lip and/or palate (CL/P) is a common congenital malformation with a complex etiology which is not fully elucidated yet. Epidemiological studies point to different etiologies in the cleft lip and palate subgroups, isolated cleft lip (CL), isolated cleft palate (CP) and combined cleft lip...... and palate (CLP). In order to understand the biological basis in these cleft lip and palate subgroups better we studied the expression profiles in human tissue from patients with CL/P. In each of the CL/P subgroups, samples were obtained from three patients and gene expression analysis was performed....... Moreover, selected differentially expressed genes were analyzed by quantitative RT-PCR, and by immunohistochemical staining of craniofacial tissue from human embryos. Osteopontin (SPP1) and other immune related genes were significantly higher expressed in palate tissue from patients with CLP compared to CP...

  19. Expression analyses of human cleft palate tissue suggest a role for osteopontin and immune related factors in palatal development

    DEFF Research Database (Denmark)

    Jakobsen, L.P.; Borup, R.; Vestergaard, J.;

    2009-01-01

    . Moreover, selected differentially expressed genes were analyzed by quantitative RT-PCR, and by immunohistochemical staining of craniofacial tissue from human embryos. Osteopontin (SPP1) and other immune related genes were significantly higher expressed in palate tissue from patients with CLP compared to CP...... and palate (CLP). In order to understand the biological basis in these cleft lip and palate subgroups better we studied the expression profiles in human tissue from patients with CL/P. In each of the CL/P subgroups, samples were obtained from three patients and gene expression analysis was performed...... and immunostaining in palatal shelves against SPP1, chemokine receptor 4 (CXCR4) and serglycin (PRG1) in human embryonic craniofacial tissue were positive, supporting a role for these genes in palatal development. However, gene expression profiles are subject to variations during growth and therefore we recommend...

  20. Cloning and characterization of carboxyl terminus of heat shock cognate 70-interacting protein gene from the silkworm, Bombyx mori.

    Science.gov (United States)

    Ohsawa, Takeshi; Fujimoto, Shota; Tsunakawa, Akane; Shibano, Yuka; Kawasaki, Hideki; Iwanaga, Masashi

    2016-11-01

    Carboxyl terminus of heat shock cognate 70-interacting protein (CHIP) is an evolutionarily conserved E3 ubiquitin ligase across different eukaryotic species and is known to play a key role in protein quality control. CHIP has two distinct functional domains, an N-terminal tetratricopeptide repeat (TPR) and a C-terminal U-box domain, which are required for the ubiquitination of numerous labile client proteins that are chaperoned by heat shock proteins (HSPs) and heat shock cognate proteins (HSCs). During our screen for CHIP-like proteins in the Bombyx mori databases, we found a novel silkworm gene, Bombyx mori CHIP. Phylogenetic analysis showed that BmCHIP belongs to Lepidopteran lineages. Quantitative reverse transcription-PCR analysis indicated that BmCHIP was relatively highly expressed in the gonad and fat body. A pull-down experiment and auto-ubiquitination assay showed that BmCHIP interacted with BmHSC70 and had E3 ligase activity. Additionally, immunohistochemical analysis revealed that BmCHIP was partially co-localized with ubiquitin in BmN4 cells. These data support that BmCHIP plays an important role in the ubiquitin proteasome system as an E3 ubiquitin ligase in B. mori.

  1. ExpI and PhzI are descendants of the long lost cognate signal synthase for SdiA.

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    Anice Sabag-Daigle

    Full Text Available SdiA of E. coli and Salmonella is a LuxR homolog that detects N-acyl homoserine lactones (AHLs. Most LuxR homologs function together with a cognate AHL synthase (a LuxI homolog, but SdiA does not. Instead, SdiA detects AHLs produced by other bacterial species. In this report, we performed a phylogenetic analysis of SdiA. The results suggest that one branch of the Enterobacteriaceae obtained a rhlR/rhlI pair by horizontal transfer. The Erwinia and Pantoea branches still contain the complete pair where it is known as expR/expI and phzR/phzI, respectively. A deletion event removed the luxI homolog from the remainder of the group, leaving just the luxR homolog known as sdiA. Thus ExpR and PhzR are SdiA orthologs and ExpI and PhzI are descendants of the long lost cognate signal synthase of SdiA.

  2. Cross-Linguistic Influence in the Bilingual Mental Lexicon: Evidence of Cognate Effects in the Phonetic Production and Processing of a Vowel Contrast.

    Science.gov (United States)

    Amengual, Mark

    2016-01-01

    The present study examines cognate effects in the phonetic production and processing of the Catalan back mid-vowel contrast (/o/-/ɔ/) by 24 early and highly proficient Spanish-Catalan bilinguals in Majorca (Spain). Participants completed a picture-naming task and a forced-choice lexical decision task in which they were presented with either words (e.g., /bɔsk/ "forest") or non-words based on real words, but with the alternate mid-vowel pair in stressed position ((*)/bosk/). The same cognate and non-cognate lexical items were included in the production and lexical decision experiments. The results indicate that even though these early bilinguals maintained the back mid-vowel contrast in their productions, they had great difficulties identifying non-words and real words based on the identity of the Catalan mid-vowel. The analyses revealed language dominance and cognate effects: Spanish-dominants exhibited higher error rates than Catalan-dominants, and production and lexical decision accuracy were also affected by cognate status. The present study contributes to the discussion of the organization of early bilinguals' dominant and non-dominant sound systems, and proposes that exemplar theoretic approaches can be extended to include bilingual lexical connections that account for the interactions between the phonetic and lexical levels of early bilingual individuals.

  3. Cross-linguistic influence in the bilingual mental lexicon: evidence of cognate effects in the phonetic production and processing of a vowel contrast

    Directory of Open Access Journals (Sweden)

    Mark eAmengual

    2016-04-01

    Full Text Available The present study examines cognate effects in the phonetic production and processing of the Catalan back mid-vowel contrast (/o/-/ɔ/ by 24 early and highly proficient Spanish-Catalan bilinguals in Majorca (Spain. Participants completed a picture-naming task and a forced-choice lexical decision task in which they were presented with either words (e.g. /bɔsk/ ‘forest’ or non-words based on real words, but with the alternate mid-vowel pair in stressed position (*/bosk/. The same cognate and non-cognate lexical items were included in the production and lexical decision experiments. The results indicate that even though these early bilinguals maintained the back mid-vowel contrast in their productions, they had great difficulties identifying non-words and real words based on the identity of the Catalan mid-vowel. The analyses revealed language dominance and cognate effects: Spanish-dominants exhibited higher error rates than Catalan-dominants, and production and lexical decision accuracy were also affected by cognate status. The present study contributes to the discussion of the organization of early bilinguals’ dominant and non-dominant sound systems, and proposes that exemplar theoretic approaches can be extended to include bilingual lexical connections that account for the interactions between the phonetic and lexical levels of early bilingual individuals.

  4. Anti-CD20 as the B cells targeting agent in the combined therapy to modulate anti-factor VIII immune responses in hemophilia A inhibitor mice

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    Chao Lien eLiu

    2014-01-01

    Full Text Available Neutralizing antibody formation against transgene products can represent a major complication following gene therapy with treatment of genetic diseases, such as hemophilia A. Although successful approaches have been developed to prevent the formation of anti-factor VIII (FVIII antibodies, innovative strategies to overcome pre-existing anti-FVIII immune responses in FVIII-primed subjects are still lacking. Anti-FVIII neutralizing antibodies circulate for long periods in part due to persistence of memory B cells. Anti-CD20 targets a variety of B cells (pre-B cells to mature/memory cells; therefore, we investigated the impact of B cell depletion on anti-FVIII immune responses in hemophilia A mice using anti-CD20 combined with regulatory T (Treg cell expansion using IL-2/IL-2mAb complexes plus rapamycin. We found that anti-CD20 alone can partially modulate anti-FVIII immune responses in both unprimed and FVIII-primed hemophilia A mice. Moreover, in mice treated with anti-CD20 + IL-2/IL-2mAb complexes + rapamycin + FVIII, anti-FVIII antibody titers were significantly reduced in comparison to mice treated with regimens targeting only B or T cells. In addition, titers remained low after a second challenge with FVIII plasmid . Treg cells and activation markers were transiently and significantly increased in the groups treated with IL-2/IL-2mAb complexes ; however,significant B cell depletion was obtained in anti-CD20-treated groups. Importantly, both FVIII-specific antibody-secreting cells and memory B cells were significantly reduced in mice treated with combination therapy. This study demonstrates that a combination regimen is highly promising as a treatment option for modulating anti-FVIII antibodies and facilitating induction of long-term tolerance to FVIII in hemophilia A mice.

  5. Thermoneutral housing is a critical factor for immune function and diet-induced obesity in C57BL/6 nude mice.

    Science.gov (United States)

    Stemmer, K; Kotzbeck, P; Zani, F; Bauer, M; Neff, C; Müller, T D; Pfluger, P T; Seeley, R J; Divanovic, S

    2015-05-01

    Obesity-related cancers represent public health burdens of the first order. Nevertheless, suitable mouse models to unravel molecular mechanisms linking obesity to human cancer are still not available. One translational model is the immunocompromised Foxn1 (winged-helix/forkead transcription factor) nude mouse transplanted with human tumor xenografts. However, most xenograft studies are conducted in nude mice on an in-bred BALB/c background that entails protection from diet-induced obesity. To overcome such resistance to obesity and its sequelae, we here propose the dual strategy of utilizing Foxn1 nude mice on a C57BL/6 background and housing them at their thermoneutral zone. C57BL/6 nude and corresponding wild-type mice, housed at 23 or 33 °C, were subjected to either low-fat diet or high-fat diet (HFD). Energy expenditure, locomotor activity, body core temperature, respiratory quotient as well as food and water intake were analyzed using indirect calorimetry. Immune function at different housing temperatures was assessed by using an in vivo cytokine capture assay. Our data clearly demonstrate that conventional housing protects C57BL/6 nude mice from HFD-induced obesity, potentially via increased energy expenditure. In contrast, HFD-fed C57BL/6 nude mice housed at thermoneutral conditions develop adiposity, increased hepatic triglyceride accumulation, adipose tissue inflammation and glucose intolerance. Moreover, increased circulating levels of lipopolysaccharide-driven cytokines suggest a greatly enhanced immune response in C57BL/6 nude mice housed at thermoneutrality. Our data reveals mild cold stress as a major modulator for energy and body weight homeostasis as well as immune function in C57BL/6 nude mice. Adjusting housing temperatures to the thermoneutral zone may ultimately be key to successfully study growth and progression of human tumors in a diet-induced obese environment.

  6. Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection

    Directory of Open Access Journals (Sweden)

    Jintao Xu

    2016-07-01

    Full Text Available Anti-tumor necrosis factor alpha (anti-TNF-α therapies have been increasingly used to treat inflammatory diseases and are associated with increased risk of invasive fungal infections, including Cryptococcus neoformans infection. Using a mouse model of cryptococcal infection, we investigated the mechanism by which disruption of early TNF-α signaling results in the development of nonprotective immunity against C. neoformans. We found that transient depletion of TNF-α inhibited pulmonary fungal clearance and enhanced extrapulmonary dissemination of C. neoformans during the adaptive phase of the immune response. Higher fungal burdens in TNF-α-depleted mice were accompanied by markedly impaired Th1 and Th17 responses in the infected lungs. Furthermore, early TNF-α depletion also resulted in disrupted transcriptional initiation of the Th17 polarization program and subsequent upregulation of Th1 genes in CD4+ T cells in the lung-associated lymph nodes (LALN of C. neoformans-infected mice. These defects in LALN T cell responses were preceded by a dramatic shift from a classical toward an alternative activation of dendritic cells (DC in the LALN of TNF-α-depleted mice. Taken together, our results indicate that early TNF-α signaling is required for optimal DC activation, and the initial Th17 response followed by Th1 transcriptional prepolarization of T cells in the LALN, which further drives the development of protective immunity against cryptococcal infection in the lungs. Thus, administration of anti-TNF-α may introduce a particularly greater risk for newly acquired fungal infections that require generation of protective Th1/Th17 responses for their containment and clearance.

  7. The immune-endocrine loop during aging: role of growth hormone and insulin-like growth factor-I.

    Science.gov (United States)

    Burgess, W; Liu, Q; Zhou, J; Tang, Q; Ozawa, A; VanHoy, R; Arkins, S; Dantzer, R; Kelley, K W

    1999-01-01

    Why a primary lymphoid organ such as the thymus involutes during aging remains a fundamental question in immunology. Aging is associated with a decrease in plasma growth hormone (somatotropin) and IGF-I, and this somatopause of aging suggests a connection between the neuroendocrine and immune systems. Several investigators have demonstrated that treatment with either growth hormone or IGF-I restores architecture of the involuted thymus gland by reversing the loss of immature cortical thymocytes and preventing the decline in thymulin synthesis that occurs in old or GH-deficient animals and humans. The proliferation, differentiation and functions of other components of the immune system, including T and B cells, macrophages and neutrophils, also demonstrate age-associated decrements that can be restored by IGF-I. Knowledge of the mechanism by which cytokines and hormones influence hematopoietic cells is critical to improving the health of aged individuals. Our laboratory has recently demonstrated that IGF-I prevents apoptosis in promyeloid cells, which subsequently permits these cells to differentiate into neutrophils. We also demonstrated that IL-4 acts much like IGF-I to promote survival of promyeloid cells and to activate the enzyme phosphatidylinositol 3'-kinase (PI 3-kinase). However, the receptors for IGF-I and IL-4 are completely different, with the intracellular beta chains of the IGF receptor possessing intrinsic tyrosine kinase activity and the alpha and gammac subunit of the heterodimeric IL-4 receptor utilizing the Janus kinase family of nonreceptor protein kinases to tyrosine phosphorylate downstream targets. Both receptors share many of the components of the PI 3-kinase signal transduction pathway, converging at the level of insulin receptor substrate-1 or insulin receptor subtrate-2 (formally known as 4PS, or IL-4 Phosphorylated Substrate). Our investigations with IGF-I and IL-4 suggest that PI 3-kinase inhibits apoptosis by maintaining high levels of

  8. Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors.

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    Katy Milne

    Full Text Available BACKGROUND: Tumor-infiltrating T cells are associated with survival in epithelial ovarian cancer (EOC, but their functional status is poorly understood, especially relative to the different risk categories and histological subtypes of EOC. METHODOLOGY/PRINCIPAL FINDINGS: Tissue microarrays containing high-grade serous, endometrioid, mucinous and clear cell tumors were analyzed immunohistochemically for the presence of lymphocytes, dendritic cells, neutrophils, macrophages, MHC class I and II, and various markers of activation and inflammation. In high-grade serous tumors from optimally debulked patients, positive associations were seen between intraepithelial cells expressing CD3, CD4, CD8, CD45RO, CD25, TIA-1, Granzyme B, FoxP3, CD20, and CD68, as well as expression of MHC class I and II by tumor cells. Disease-specific survival was positively associated with the markers CD8, CD3, FoxP3, TIA-1, CD20, MHC class I and class II. In other histological subtypes, immune infiltrates were less prevalent, and the only markers associated with survival were MHC class II (positive association in endometrioid cases and myeloperoxidase (negative association in clear cell cases. CONCLUSIONS/SIGNIFICANCE: Host immune responses to EOC vary widely according to histological subtype and the extent of residual disease. TIA-1, FoxP3 and CD20 emerge as new positive prognostic factors in high-grade serous EOC from optimally debulked patients.

  9. Selected scientific aspects of marathon racing. An update on fluid replacement, immune function, psychological factors and the gender difference.

    Science.gov (United States)

    Sparling, P B; Nieman, D C; O'Connor, P J

    1993-02-01

    Four topics are addressed: fluid/fuel replacement during the marathon, marathoning and susceptibility to infection, psychological aspects of elite marathoners and the gender gap in marathon performance. Although these topics are diverse, they all relate to practical questions raised by coaches and athletes. Evidence from laboratory and field studies indicates that it is advisable for marathoners to consume 800 to 1000 L/h of sports drink providing 45 to 60 g/h of carbohydrate. It is strongly suggested to practice fluid consumption during training sessions as it is probable that tolerance to drinking during running is a trainable adaptation. Epidemiological and clinical research support the concept that marathon training and racing increase the runner's risk of upper respiratory tract infections because of negative changes in immune function. Susceptibility to infection may be reduced by proper nutrition, adequate sleep, appropriate recovery between vigorous workouts and minimal exposure to sick people during periods of heavy training and major races. Although psychological research in this area is still limited, evidence suggests that elite marathoners rely primarily on associative strategies during competition while judiciously dissociating in order to cope with pain. It is recommended that coaches and athletes interested in employing psychological interventions seek assistance from professionals well trained in the fields of both psychology and exercise science. Will women soon outrun men? Over the past 2 decades societal views and training practices of women distance runners have changed greatly, yet certain performance-related biological differences between men and women are unlikely to change.

  10. [Risk factors for long-term result of endovascular treatment for auto-immune disease related abdominal aorta pseudo-aneurysm].

    Science.gov (United States)

    Ye, W; Di, X; Liu, Q; Li, Y J; Zheng, Y H; Zeng, R; Song, X J; Liu, Z L; Liu, C W

    2016-12-06

    found during follow-up. There were 3 deaths during follow-up, with 1 aneurysm related death, the rest died due to other reasons. Single factors logical regressions analysis showed discontinuing immune medicine therapy and age no less than 40 years significantly related long-term MACE(Pimmune disease, none classical EVAR were not significant related to MACE. Conclusions: Endovascular therapy is safe and effective for AIPA. Regular peri-operation and long-term immunotherapy is key to success.

  11. Binding of vitronectin and Factor H to Hic contributes to immune evasion of Streptococcus pneumoniae serotype 3.

    Science.gov (United States)

    Kohler, Sylvia; Hallström, Teresia; Singh, Birendra; Riesbeck, Kristian; Spartà, Giuseppina; Zipfel, Peter F; Hammerschmidt, Sven

    2015-01-01

    Streptococcus pneumoniae serotype 3 strains are highly resistant to opsonophagocytosis due to recruitment of the complement inhibitor Factor H via Hic, a member of the pneumococcal surface protein C (PspC) family. In this study, we demonstrated that Hic also interacts with vitronectin, a fluid-phase regulator involved in haemostasis, angiogenesis, and the terminal complement cascade as well as a component of the extracellular matrix. Blocking of Hic by specific antiserum or genetic deletion significantly reduced pneumococcal binding to soluble and immobilised vitronectin and to Factor H, respectively. In parallel, ectopic expression of Hic on the surface of Lactococcus lactis conferred binding to soluble and immobilised vitronectin as well as Factor H. Molecular analyses with truncated Hic fragments narrowed down the vitronectin-binding site to the central core of Hic (aa 151-201). This vitronectin-binding region is separate from that of Factor H, which binds to the N-terminus of Hic (aa 38-92). Binding of pneumococcal Hic was localised to the C-terminal heparin-binding domain (HBD3) of vitronectin. However, an N-terminal region to HBD3 was further involved in Hic-binding to immobilised vitronectin. Finally, vitronectin bound to Hic was functionally active and inhibited formation of the terminal complement complex. In conclusion, Hic interacts with vitronectin and simultaneously with Factor H, and both human proteins may contribute to colonisation and invasive disease caused by serotype 3 pneumococci.

  12. A Rac1 GTPase is a critical factor in the immune response of shrimp (Litopenaeus vannamei) to Vibrio alginolyticus infection.

    Science.gov (United States)

    Cha, Gui-Hong; Wang, Wei-Na; Peng, Ting; Huang, Ming-Zhu; Liu, Yuan

    2015-08-01

    The small GTPase Rac1 acts as a molecular switch for signal transduction that regulates various cellular functions. However, its functions in crustaceans remain unclear. In this study, a cDNA encoding a RAS GTPase (LvRac1) in the Pacific white shrimp (L. vannamei) was identified and characterized. A recombinant variant of this GTPase, rLvRac1, was expressed in the model organism P. pastoris and its expression was confirmed by mass spectrometry. Biochemical assays indicated that the recombinant protein retained GTPase activity and was expressed in all of the organism's tested tissues. Injection of the bacterium V. alginolyticus into L. vannamei induced hepatopancreatic upregulation of LvRac1 expression. Moreover, knocking down LvRac1 in vivo significantly reduced the expression of the L. vannamei p53 and Cu/Zn superoxide dismutase genes (Lvp53 and LvCu/Zn SOD, respectively) while increasing that of the galectin gene (Lvgal). Hemolymph samples from control and LvRac1-silenced L. vannamei individuals were analyzed by flow cytometry, revealing that the latter exhibited significantly reduced respiratory burst activity and total hemocyte counts. Cumulative mortality in shrimp lacking LvRac1 was significantly greater than in control groups following V. alginolyticus challenge. The silencing of LvRac1 by double-stranded RNA injection thus increased the V. alginolyticus challenge sensitivity of L. vannamei and weakened its bacterial clearance ability in vivo. Suppressing LvRac1 also promoted the upregulation of Lvp53, LvCu/ZnSOD, and Lvgal following V. alginolyticus injection. Taken together, these results suggest that LvRac1 is important in the innate immune response of shrimp to V. alginolyticus infection.

  13. Modulation of immune response, physical barrier and related signaling factors in the gills of juvenile grass carp (Ctenopharyngodon idella) fed supplemented diet with phospholipids.

    Science.gov (United States)

    Feng, Lin; Chen, Yong-Po; Jiang, Wei-Dan; Liu, Yang; Jiang, Jun; Wu, Pei; Zhao, Juan; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu

    2016-01-01

    This study was conducted to investigate the effects of dietary phospholipids (PL) on the gill immune response and physical barrier of juvenile grass carp (Ctenopharyngodon idella). A total of 1080 juvenile grass carp with an average initial weight of 9.34 ± 0.03 g were fed six semi-purified diets containing 0.40% (unsupplemented control group), 1.43%, 2.38%, 3.29%, 4.37% and 5.42% PL for 2 months. Compared with the control group, optimal PL supplementation increased (P < 0.05): (1) the lysozyme activity, acid phosphatase activity, complement component 3 (C3) content, liver expressed antimicrobial peptide 1 (LEAP-1) and LEAP-2 mRNA expression; (2) the relative mRNA expression of interleukin 10, transforming growth factor β1, inhibitor factor κBα (IκBα) and target of rapamycin (TOR); (3) the activities of anti-superoxide anion (ASA), anti-hydroxyl radical (AHR), copper/zinc superoxide dismutase (SOD1), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), glutathione content and mRNA levels of SOD1, CAT, GPx, GR and NF-E2-related factor 2 (Nrf2) genes; (4) the transcription abundance of occludin, claudin b, claudin c, claudin 12 and zonula occludens 1 genes. At the same time, appropriate PL supplementation decreased (P < 0.05): (1) tumor necrosis factor α, interleukin 1β, nuclear factor κB p65 (NF-κB p65), IκB kinase β (IKKβ) and IκB kinase γ (IKKγ) mRNA expression; (2) malondialdehyde (MDA), protein carbonyl (PC) and reactive oxygen species (ROS) content and the relative mRNA expression of Kelch-like-ECH-associated protein 1a (Keap1a) and Keap1b; (3) the transcription abundance of myosin light chain kinase (MLCK) and p38 mitogen-activated protein kinase (p38 MAPK) genes. In conclusion, the positive effect of PL on gill health is associated with the improvement of the immunity, antioxidant status and tight junction barrier of fish gills. Finally, based on ACP activity, C3 content, PC content and ASA activity in the gills

  14. Bazex Syndrome in Lung Squamous Cell Carcinoma: High Expression of Epidermal Growth Factor Receptor in Lesional Keratinocytes with Th2 Immune Shift

    Science.gov (United States)

    Amano, Maki; Hanafusa, Takaaki; Chikazawa, Sakiko; Ueno, Makiko; Namiki, Takeshi; Igawa, Ken; Miura, Keiko; Yokozeki, Hiroo

    2016-01-01

    An 82-year-old Japanese man was referred for detailed examination of hyperkeratotic erythematous plaques on his palms and soles for 6 months. Two weeks before his first visit, he had undergone lung lobectomy for right lung squamous cell carcinoma (SCC). Laboratory findings showed elevations of eosinophil counts, serum IgE, thymus and activation-regulated chemokine, SCC antigen, and soluble interleukin-2 receptor levels. Histological results of a skin biopsy involving the left palm showed psoriasiform dermatitis. Before lung lobectomy, the hyperkeratotic erythematous plaques on the palms and soles and the erythemas on the trunk and extremities were difficult to treat with topical steroids. After lobectomy, the skin symptoms dramatically and rapidly subsided with topical steroids. Therefore, we diagnosed Bazex syndrome (BS), also known as acrokeratosis paraneoplastica, as a paraneoplastic cutaneous disease in lung SCC. The mild eosinophilia subsided and levels of SCC antigen, IgE, and soluble interleukin-2 receptor were reduced. BS is a paraneoplastic cutaneous disease characterized by acral psoriasiform lesions associated with an underlying neoplasm. In a previous report, a shift to the Th2 immune condition was found in patients with non-small cell lung cancer, as shown in our patient. Epidermal growth factor receptor (EGFR) is also known as tumor growth factor-α receptor; it is increased in psoriatic keratinocytes. In our case, EGFR expression increased in lesional keratinocytes 2 weeks after surgery and decreased 4 weeks after surgery. We speculate that a shift to Th2 immune reactions in lung SCC may be the pathogenesis of BS, whereby lesional keratinocytes highly express EGFR in parallel with disease activity. PMID:28101024

  15. Nucleosome Presence at AML-1 Binding Sites Inversely Correlates with Ly49 Expression: Revelations from an Informatics Analysis of Nucleosomes and Immune Cell Transcription Factors.

    Science.gov (United States)

    Wight, Andrew; Yang, Doo; Ioshikhes, Ilya; Makrigiannis, Andrew P

    2016-04-01

    Beyond its role in genomic organization and compaction, the nucleosome is believed to participate in the regulation of gene transcription. Here, we report a computational method to evaluate the nucleosome sensitivity for a transcription factor over a given stretch of the genome. Sensitive factors are predicted to be those with binding sites preferentially contained within nucleosome boundaries and lacking 10 bp periodicity. Based on these criteria, the Acute Myeloid Leukemia-1a (AML-1a) transcription factor, a regulator of immune gene expression, was identified as potentially sensitive to nucleosomal regulation within the mouse Ly49 gene family. This result was confirmed in RMA, a cell line with natural expression of Ly49, using MNase-Seq to generate a nucleosome map of chromosome 6, where the Ly49 gene family is located. Analysis of this map revealed a specific depletion of nucleosomes at AML-1a binding sites in the expressed Ly49A when compared to the other, silent Ly49 genes. Our data suggest that nucleosome-based regulation contributes to the expression of Ly49 genes, and we propose that this method of predicting nucleosome sensitivity could aid in dissecting the regulatory role of nucleosomes in general.

  16. Complement factor I deficiency: a not so rare immune defect. Characterization of new mutations and the first large gene deletion

    Directory of Open Access Journals (Sweden)

    Alba-Domínguez María

    2012-06-01

    Full Text Available Abstract Background Complement Factor I (CFI is a serine protease with an important role in complement alternative pathway regulation. Complete factor I deficiency is strongly associated with severe infections. Approximately 30 families with this deficiency have been described worldwide. Patients and methods We have studied five new Spanish families suffering from CFI deficiency. From 19 screened people, 7 homozygous, 10 heterozygous and 2 healthy subjects were identified. Clinical, biochemical and genetic descriptions are included. Results Molecular studies demonstrated 4 novel mutations in the screened individuals; amongst them, we describe here the first great gene deletion reported in the CFI locus, which includes full exon 2 and part of the large intron 1. Conclusion CFI deficiency is possibly an underestimated defect and the eventual existence of this deficiency should be tested in those patients exhibiting low C3 and recurrent bacterial infections. We propose a simple diagnostic flowchart to help clinicians in the identification and correct diagnosis of such patients.

  17. Immune System

    NARCIS (Netherlands)

    Kuper, C.F.; Ruehl-Fehlert, C.; Elmore, S.A.; Parker, G.A.

    2013-01-01

    Cells of the immune system are found in every organ, from the classic lymphoid organs to tissues such as liver, mucosae, and omental adipose tissue. Toxicity to the immune system may be from a direct or indirect injury to lymphoid organs. The morphological responses range from lymphocyte depletion t

  18. Immune System

    Science.gov (United States)

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

  19. Tissue Factor in Dermatitis Herpetiformis and Bullous Pemphigoid: Link between Immune and Coagulation System in Subepidermal Autoimmune Bullous Diseases

    Directory of Open Access Journals (Sweden)

    Agnieszka Zebrowska

    2015-01-01

    Full Text Available Dermatitis herpetiformis (DH and bullous pemphigoid (BP are skin diseases associated with eosinophilic and neutrophilic infiltrations. Although chemokines are critical for the selective accumulation and activation of various leukocyte subsets in the inflammatory process, there are few findings concerning inflammatory cells and production of coagulation factors in blistering diseases. Skin biopsies were taken from 14 patients with DH, 27 with BP, and 20 control subjects. The localization and expression of tissue factor (TF in skin lesions and perilesional skin were studied by immunohistochemistry and confirmed by Western Blot. Moreover the plasma concentrations of TF were measured by immunoassays. D dimers, fibrinogen, and selected coagulation parameters were measured by routine methods. Expression of TF in the epidermis and in inflammatory influxed cells in dermis was detected in skin biopsies from BP patients. Examined TF expression was detected in perilesional skin of all BP patients too. The expression of TF was not observed in biopsies from healthy people and DH patients. The findings of the study show an increased expression of tissue factor in the lesional and perilesional skin of patients with bullous pemphigoid. The difference in chemokine pattern expression and variations in the cellular infiltration in BP and DH cause variable expression of TF.

  20. Mesenchymal stromal cells expressing ErbB-2/neu elicit protective antibreast tumor immunity in vivo, which is paradoxically suppressed by IFN-gamma and tumor necrosis factor-alpha priming.

    Science.gov (United States)

    Romieu-Mourez, Raphaëlle; François, Moïra; Abate, Amanda; Boivin, Marie-Noëlle; Birman, Elena; Bailey, Dana; Bramson, Jonathan L; Forner, Kathy; Young, Yoon-Kow; Medin, Jeffrey A; Galipeau, Jacques

    2010-10-15

    It is unknown whether mesenchymal stromal cells (MSC) can regulate immune responses targeting tumor autoantigens of low immunogenicity. We tested here whether immunization with MSC could break immune tolerance towards the ErbB-2/HER-2/neu tumor antigen and the effects of priming with IFN-γ and tumor necrosis factor-α (TNF-α) on this process. BALB/c- and C57BL/6-derived MSC were lentivirally transduced to express a kinase-inactive rat neu mutant (MSC/Neu). Immunization of BALB/c mice with nontreated or IFN-γ-primed allogeneic or syngeneic MSC/Neu induced similar levels of anti-neu antibody titers; however, only syngeneic MSC/Neu induced protective neu-specific CD8(+) T cell responses. Compared to immunization with nontreated or IFN-γ-primed syngeneic MSC/Neu, the number of circulating neu-specific CD8(+) T cells and titers of anti-neu antibodies were observed to be decreased after immunizations with IFN-γ- plus TNF-α-primed MSC/Neu. In addition, syngeneic MSC/Neu seemed more efficient than IFN-γ-primed MSC/Neu at inducing a protective therapeutic antitumor immune response resulting in the regression of transplanted neu-expressing mammary tumor cells. In vitro antigen-presenting cell assays performed with paraformaldehyde-fixed or live MSC showed that priming with IFN-γ plus TNF-α, compared to priming with IFN-γ alone, increased antigen presentation as well as the production of immunosuppressive factors. These data suggest that whereas MSC could effectively serve as antigen-presenting cells to induce immune responses aimed at tumor autoantigens, these functions are critically regulated by IFN-γ and TNF-α.

  1. Cloning Changes the Response to Obesity of Innate Immune Factors in Blood, Liver, and Adipose Tissues in Domestic Pigs

    DEFF Research Database (Denmark)

    Højbøge, Tina Rødgaard; Skovgaard, Kerstin; Stagsted, Jan

    2013-01-01

    factors were analyzed in lean and diet-induced obese cloned domestic pigs and compared to normal domestic pigs (obese and lean). The number of genes affected by obesity was lower in cloned animals than in control animals. All genes affected by obesity in adipose tissues of clones were downregulated; both......-differentiated gene expression, concomitantly with an increase in APP serum concentrations only seen in cloned, obese pigs. This may suggest that the APP response seen in obese, cloned pigs is a consequence of the characteristic skewed gene response to obesity in cloned pigs, as described in this work. This should...

  2. Roles of monocyte chemotactic protein 1 and nuclear factor-κB in immune response to spinal tuberculosis in a New Zealand white rabbit model

    Science.gov (United States)

    Guo, X.H.; Bai, Z.; Qiang, B.; Bu, F.H.; Zhao, N.

    2017-01-01

    This study aimed to explore the roles of monocyte chemotactic protein 1 (MCP-1) and nuclear factor kappa B (NF-κB) in immune response to spinal tuberculosis in a New Zealand white rabbit model. Forty-eight New Zealand white rabbits were collected and divided into four groups: experimental group (n=30, spinal tuberculosis model was established), the sham group (n=15, sham operation was performed) and the blank group (n=3). The qRT-PCR assay and western blotting were applied to detect the mRNA and protein expressions of MCP-1 and NF-κB in peripheral blood. ELISA was used to measure serum levels of MCP-1, NF-κB, IFN-γ, IL-2, IL-4, and IL-10. Flow cytometry was adopted to assess the distributions of CD4+, CD8+ lymphocytes and CD4+ CD25+ Foxp3 lymphocyte subsets. Compared with the sham and blank groups, the mRNA and protein expressions of MCP-1 and NF-κB in the experimental group were significantly increased. The experimental group had lower serum levels of IL-2 and IFN-γ and higher serum level of IL-10 than the sham and blank groups. In comparison to the sham and blank groups, CD4+ T lymphocyte subsets percentage, CD4+/CD8+ ratio and CD4+ CD25+ Foxp3+ Tregs subsets accounting for CD4+ lymphocyte in the experimental group were lower, while percentage of CD8+ T lymphocyte subsets was higher. Our study provided evidence that higher expression of MCP-1 and NF-κB may be associated with decreased immune function of spinal tuberculosis, which can provide a new treatment direction for spinal tuberculosis. PMID:28225889

  3. Anti-lipopolysaccharide factor in Litopenaeus vannamei (LvALF): a broad spectrum antimicrobial peptide essential for shrimp immunity against bacterial and fungal infection.

    Science.gov (United States)

    de la Vega, Enrique; O'Leary, Nuala A; Shockey, Jessica E; Robalino, Javier; Payne, Caroline; Browdy, Craig L; Warr, Gregory W; Gross, Paul S

    2008-04-01

    Antimicrobial peptides are an essential component of the innate immune system of most organisms. Expressed sequence tag analysis from various shrimp (Litopenaeus vannamei) tissues revealed transcripts corresponding to two distinct sequences (LvALF1 and LvALF2) with strong sequence similarity to anti-lipopolysaccharide factor (ALF), an antimicrobial peptide originally isolated from the horseshoe crab Limulus polyphemus. Full-length clones contained a 528bp transcript with a predicted open reading frame coding for 120 amino acids in LvALF1, and a 623bp transcript with a predicted open reading frame coding for 93 amino acids in LvALF2. A reverse genetic approach was implemented to study the in vivo role of LvALF1 in protecting shrimp from bacterial, fungal and viral infections. Injection of double-stranded RNA (dsRNA) corresponding to the LvALF1 message resulted in a significant reduction of LvALF1 mRNA transcript abundance as determined by qPCR. Following knockdown, shrimp were challenged with low pathogenic doses of Vibrio penaeicida, Fusarium oxysporum or white spot syndrome virus (WSSV) and the resulting mortality curves were compared with controls. A significant increase of mortality in the LvALF1 knockdown shrimp was observed in the V. penaeicida and F. oxysporum infections when compared to controls, showing that this gene has a role in protecting shrimp from both bacterial and fungal infections. In contrast, LvALF1 dsRNA activated the sequence-independent innate anti-viral immune response giving increased protection from WSSV infection.

  4. Successful immune tolerance induction with low-dose coagulation factor VIII in a patient with hemophilia A from a developing country.

    Science.gov (United States)

    Ay, Yilmaz; Ersin, Toret; Yesim, Oymak; Hilkay, Karapinar Tuba; Dilek, Ince; Gulcihan, Ozek; Ahmet, Koc

    2016-09-01

    Inhibitor development is the most frequent and serious complication of the treatment in patients with hemophilia. Immune tolerance induction (ITI) is the only option of treatment for the eradication of factor VIII (FVIII) inhibitor. We would like to present our case with hemophilia whose FVIII inhibitor eradication was done by a low-dose ITI regimen. Our patient has been applied on-demand therapy until 8 years of age. Secondary prophylaxis was began because of having hemophilic arthropathy. A low titer of FVIII inhibitor (4.2 BU/ml) was detected in the fifth month of the prophylaxis. The peak inhibitor titer of patient was 4.6 BU/ml, and there was no decrease in inhibitor titer in the follow-up duration. The low-dose ITI (50 IU/kg, 3 days a week) was started. His inhibitor level was detected negative and the recovery test was ameliorated in the 15th of the ITI therapy. High-dose regimen ITI could not be given particularly in developing countries such as Turkey in view of the high cost of treatment. Patients who had good risk factors might be successfully treated by using low-dose ITI regimen as effective as high-dose ITI regimen.

  5. Capsicum annuum WRKYb transcription factor that binds to the CaPR-10 promoter functions as a positive regulator in innate immunity upon TMV infection.

    Science.gov (United States)

    Lim, Jee Hyuck; Park, Chang-Jin; Huh, Sung Un; Choi, La Mee; Lee, Gil Je; Kim, Young Jin; Paek, Kyung-Hee

    2011-08-05

    In plant, some WRKY transcription factors are known to play an important role in the transcriptional reprogramming associated with the immune response. By using WRKY-domain-specific differential display procedure, we isolated CaWRKYb gene, which is rapidly induced during an incompatible interaction between hot pepper and Tobacco mosaic virus (TMV) pathotype P(0) infection. The recombinant CaWRKYb bound to the W box-containing CaPR-10 promoter probes efficiently and the specificity of binding was confirmed by mutant study and competition with cold oligonucleotides. Also, in GUS reporter activity assay using Arabidopsis protoplasts with the CaPR-10 promoter, GUS activity was increased in the presence of CaWRKYb. And CaWRKYb-knockdown plant showed reduced number of hypersensitive response local lesions upon TMV-P(0) infection. Furthermore, CaWRKYb-knockdown plant exhibited compromised resistance to TMV-P(0) by accumulating more TMV, apparently through decreased expression of CaPR-10, CaPR-1, and CaPR-5. These results suggest that CaWRKYb is involved as a positive transcription factor in defense-related signal transduction pathways in hot pepper. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Transforming Growth Factor Beta Is a Major Regulator of Human Neonatal Immune Responses following Respiratory Syncytial Virus Infection▿ †

    Science.gov (United States)

    Thornburg, Natalie J.; Shepherd, Bryan; Crowe, James E.

    2010-01-01

    Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality. Previous studies have suggested that T-cell responses may contribute to RSV immunopathology, which could be driven by dendritic cells (DCs). DCs are productively infected by RSV, and during RSV infections, there is an increase of DCs in the lungs with a decrease in the blood. Pediatric populations are particularly susceptible to severe RSV infections; however, DC responses to RSV from pediatric populations have not been examined. In this study, primary isolated DCs from cord blood and adult peripheral blood were compared after RSV infection. Transcriptional profiling and biological network analysis identified transforming growth factor beta (TGF-β) and associated signaling molecules as differentially regulated in the two age groups. TGF-β1 was decreased in RSV-infected adult-blood DCs but increased in RSV-infected cord blood DCs. Coculture of adult RSV-infected DCs with autologous T cells induced secretion of gamma interferon (IFN-γ), interleukin 12p70 (IL-12p70), IL-2, and tumor necrosis factor alpha (TNF-α). Conversely, coculture of cord RSV-infected DCs and autologous T cells induced secretion of IL-4, IL-6, IL-1β, and IL-17. Addition of purified TGF-β1 to adult DC-T-cell cocultures reduced secretion of IFN-γ, IL-12p70, IL-2, and TNF-α, while addition of a TGF-β chemical inhibitor to cord DC-T-cell cocultures increased secretion of IL-12p70. These data suggest that TGF-β acts as a major regulator of RSV DC-T-cell responses, which could contribute to immunopathology during infancy. PMID:20926560

  7. Latin, the Key to English Vocabulary. A Gamebook on English Derivatives and Cognates to Accompany "Voces de Olympo" (Echoes from Mt. Olympus).

    Science.gov (United States)

    Masciantonio, Rudolph

    This gamebook is intended to assist the grade school (FLES) Latin teacher to introduce the reading and writing of English derivatives and cognates after these have been mastered audiolingually in Philadelphia's Latin course "Voces de Olympo (Echoes from Mt. Olympus): A Humanistic Approach to Latin for Children in the Sixth Grade." Games are…

  8. Phosphorolytic activity of Escherichia coli glycyl-tRNA synthetase towards its cognate aminoacyl adenylate detected by 31P-NMR spectroscopy and thin-layer chromatography

    DEFF Research Database (Denmark)

    Led, Jens Jørgen; Switon, Werner K.; Jensen, Kaj Frank

    1983-01-01

    The catalytic activity of highly purified Escherichia coli glycyl-tRNA synthetase has been studied by 31P-NMR spectroscopy and thin-layer chromatography on poly(ethyleneimine)-cellulose. It was found that this synthetase, besides the activation of its cognate amino acid and the syntheses...

  9. What Is a TOT? Cognate and Translation Effects on Tip-of-the-Tongue States in Spanish-English and Tagalog-English Bilinguals

    Science.gov (United States)

    Gollan, Tamar H.; Acenas, Lori-Ann R.

    2004-01-01

    The authors induced tip-of-the-tongue states (TOTs) for English words in monolinguals and bilinguals using picture stimuli with cognate (e.g., vampire, which is vampiro in Spanish) and noncognate (e.g., funnel, which is embudo in Spanish) names. Bilinguals had more TOTs than did monolinguals unless the target pictures had translatable cognate…

  10. Factors Influencing the Choice of Child Delivery Location among Women Attending Antenatal Care Services and Immunization Clinic in Southeastern Nigeria.

    Science.gov (United States)

    Egharevba, Johnbull; Pharr, Jennifer; van Wyk, Brian; Ezeanolue, Echezona

    2017-01-01

    In Nigeria, most deliveries take place at home or with traditional birth attendants (TBAs). This study examined the factors that influenced or determined utilization of healthcare facility delivery services among women who attended antenatal care (ANC) services. A cross-sectional survey was conducted with 220 women who registered for ANC at a hospital and delivered within 18 months. Associations between independent variables and choice of healthcare facility delivery were analyzed. Multiple logistic regression was also used to identify the predictors of choice of delivery among women. Of the 220 women who registered for ANC, 75% delivered at a healthcare facility while 15% delivered with a TBA or at home. In the final model, number of children, having planned to deliver at a hospital, labor occurring at night, and labor allowing time for transportation were significant predictors of child delivery location among the women. Utilization of the health facilities for childbirth may increase if pregnant women are encouraged to book early for ANC and if during ANC, pregnant women were counseled to detect labor signs early. In addition to focused and intensified counseling for women with more children, support should be provided that includes financial provisions for transportation to the healthcare facility.

  11. Immunization Coverage

    Science.gov (United States)

    ... Brazil, the Democratic Republic of the Congo, Ethiopia, India, Indonesia, Iraq, Nigeria, Pakistan and South Africa. Monitoring ... information on vaccines and immunization You are here: Media centre Fact sheets Quick Links Sitemap Home Health ...

  12. The role of tumor necrosis factor receptor-associated factor nuclear factor-κB-binding kinase 1 and stimulator of interferon genes mediated immune responses to DNA vaccines%肿瘤坏死因子受体相关因子联合核因子-κB激酶结合激酶1和干扰素刺激因子基因在介导DNA疫苗免疫中的作用

    Institute of Scientific and Technical Information of China (English)

    宿凌恺

    2012-01-01

    Tumor necrosis factor receptor-associated factor nuclear factor-KB-binding kinase 1 (TBK1) are already proved to play an important role in mediating immune responses to DNA vaccines, not only adaptive immune responses including cellular immunity and humoral immunity, but also innate immune responses. Recently, it is reported that stimulator of interferon genes (STING) is a significant element for the production of type I interferon to regulate innate immunity, which is mediated by TBK1. In this review, the role of TBK1 mediated immune responses to DNA vaccines and the role of STING gene mediated innate immune responses to TBK1 were introduced.%肿瘤坏死因子受体相关因子联合核因子-κB激酶结合激酶1(TBK1)基因不但在DNA疫苗诱导体液免疫和细胞免疫等特异性免疫时发挥着重要的作用,而且在诱导固有免疫方面也有其独特的作用.干扰素刺激因子基因(STING)是TBK1基因诱导I型干扰素产生从而在固有免疫反应时不可缺少的组分.本文就TBK1 和STING基因在介导DNA疫苗免疫中的作用作一综述.

  13. Identification of innate immune antiretroviral factors during in vivo and in vitro exposure to HIV-1.

    Science.gov (United States)

    Zapata, Wildeman; Aguilar-Jiménez, Wbeimar; Feng, Zhimin; Weinberg, Aaron; Russo, Aniello; Potenza, Nicoletta; Estrada, Hernando; Rugeles, María T

    2016-03-01

    Defensins, RNases and cytokines are present at mucosal barriers, main ports of HIV entry, and are potential mediators of the resistant phenotype exhibited by HIV-1-exposed seronegative individuals (HESN) during sexual exposure. We aimed to determine the role of soluble factors in natural resistance to HIV-1 infection. Vaginal/endocervical/oral mucosal samples were taken from 60 HESN, 60 seropositive (SP) and 61 healthy controls (HC). Human neutrophil peptide 1 (hNP-1), human beta defensin (hBD) 2 and 3, RNases, MIP-1β and RANTES mRNA transcripts were quantified by qPCR and in vitro single-round, recombinant-based viral infectivity assay was used to evaluate the anti-HIV-1 activity of hBDs and RNases. HESN expressed significantly higher levels of hNP-1, hBDs mRNA in oral mucosa compared to HC (P < 0.05). In genital mucosa, significantly higher mRNA levels of MIP-1β, RANTES and RNases were found in HESN compared to HC (P < 0.05). HBDs and RNases inhibit HIV-1 replication, particularly R5 at entry, reverse transcription and nuclear import of the viral life cycle. hNP-1, hBDs, MIP-1β, RANTES and RNases, collectively could contribute to HIV-1 resistance during sexual exposure. Moreover, the inhibition of HIV-1 infection in vitro by hBDs and RNases suggests that they may be exploited as potential antiretrovirals.

  14. The Allograft Inflammatory Factor-1 (AIF-1 homologous in Hirudo medicinalis (medicinal leech is involved in immune response during wound healing and graft rejection processes

    Directory of Open Access Journals (Sweden)

    T Schorn

    2015-05-01

    Full Text Available Allograft inflammatory factor-1 (AIF-1 is a 17 kDa cytokine-inducible calcium-binding protein that in Vertebrates plays an important role in allografts immune response. Since its expression is mainly limited to the monocyte/macrophage lineage, it was recently suggested that it could play a key role during inflammatory responses, allograft rejection, as well as in the activation of macrophages. To clarify this point we have focused our research on the possible role of AIF-1 during the inflammatory response after injury in the leech Hirudo medicinalis (Annelida, Hirudinea. This invertebrate is an excellent animal model since the responses evoked during inflammation and tissue repair are clear and easily detectable and have a striking similarity with vertebrate responses. Moreover the analysis of an EST library from H. medicinalis CNS, revealed the presence of a gene, named Hmaif-1/alias Hmiba1, showing a high homology with vertebrate aif-1. Our data show that the related protein, named HmAIF-1, is constitutively expressed in unlesioned leeches and that dramatically increases 48 h after wounds and tissue transplants. Immunohistochemistry experiments, using a specific anti HmAIF-1 polyclonal antibody, shows that this factor is present in spread, CD68+ /CD45+ macrophage-like cells. A few days after experimental wounding of the body wall, the amount of these immunopositive cells increases at the lesion site. In conclusion here we propose that in leech HmAIF-1 factor is involved in inflammation events like its vertebrate counterparts.

  15. First molluscan transcription factor activator protein-1 (Ap-1) member from disk abalone and its expression profiling against immune challenge and tissue injury.

    Science.gov (United States)

    De Zoysa, Mahanama; Nikapitiya, Chamilani; Lee, Youngdeuk; Lee, Sukkyoung; Oh, Chulhong; Whang, Ilson; Yeo, Sang-Yeop; Choi, Cheol Young; Lee, Jehee

    2010-12-01

    The regulation of transcriptional activation is an essential and critical point in gene expression. In this study, we describe a novel transcription factor activator protein-1 (Ap-1) gene from disk abalone Haliotis discus discus (AbAp-1) for the first time in mollusk. It was identified by homology screening of an abalone normalized cDNA library. The cloned AbAp-1 consists of a 945 bp coding region that encodes a putative protein containing 315 amino acids. The AbAp-1 gene is composed of a characteristic Jun transcription factor domain and a highly conserved basic leucine zipper (bZIP) signature similar to known Ap-1 genes. The AbAp-1 shares 46, 43 and, 40% amino acid identities with fish (Takifugu rubripes), human and insect (Ixodes scapularis) Ap-1, respectively. Quantitative real time RT-PCR analysis confirmed that AbAp-1 gene expression is constitutive in all selected tissues. AbAp-1 was upregulated in gills after bacteria (Vibrio alginolyticus, Vibrio parahemolyticus and Lysteria monocytogenes) challenge; and, upregulated in hemocytes and gills by viral hemorrhagic septicemia virus (VHSV) challenge. Shell damage and tissue injury also increased the transcriptional level of Ap-1 in mantle together with other transcription factors (NF-kB, LITAF) and pro-inflammatory TNF-α. All results considered, identification and gene expression data demonstrate that abalone Ap-1 is an important regulator in innate immune response against bacteria and virus, as well as in the inflammatory response during tissue injury. In addition, stimulation of Ap-1 under different external stimuli could be useful to understand the Ap-1 biology and its downstream target genes, especially in abalone-like mollusks.

  16. Hepatitis B vaccination in haemodialysis patients: an underestimated problem. Factors influencing immune responses in ten years of observation in an Italian haemodialysis centre and literature review.

    Science.gov (United States)

    Cordova, E; Miglia, I; Festuccia, F; Sarlo, M G; Scornavacca, G; Punzo, G; Menè, P; Fofi, C

    2017-01-01

    Despite universal infection control precautions, the risk of hepatitis B virus (HBV) infection in patients on chronic haemodialysis (HD) remains high. For this reason anti-HBV vaccination is recommended in these subjects. In hemodialyzed patients vaccinal response is often suboptimal and it's not clear what factors may influence it. The aim of our study is to assess the influence of some clinical and laboratory factors on seroconversion rate after anti HBV vaccination in a cohort of patients on maintenance HD. We analysed 60 patients on regular HD, 40 men and 20 women (age 64±12 years, range 40-88 years), immunized with Engerix B ® vaccine, followed for an average time of 62 month (12-120 months). For each patient the following data were collected: age, serum albumin (sAlb), Blood urea nitrogen before HD session (BUN), age at vaccination, dialysis vintage, presence of systemic disease, type of vascular access, dialysis modality. Correlation between these factors and anti Hbs titer was estimated with multiple regression analysis. Anti-Hbs seroconversion rate ( Anti Hbs > 10 IU/l) was 77%. Better rate of seroconversion (86%) was observed in patients with arteriovenous fistula (AVF) and serum albumin > 3,5 g/dL (93%), while higher rate of not responders (50%) in patients with systemic diseases. The only parameter correlated to anti Hbs titer was sAlb (p =0,0012). sAlb was correlated to age in all patients (p=0,01) and age was correlated to higher anti Hbs titer in the responder group (p=0,018). In our experience an early vaccination, when patients on chronic HD are younger and in better nutritional conditions, improves anti-HBV response.

  17. Identification of orange-spotted grouper (Epinephelus coioides) interferon regulatory factor 3 involved in antiviral immune response against fish RNA virus.

    Science.gov (United States)

    Huang, Youhua; Huang, Xiaohong; Cai, Jia; OuYang, Zhengliang; Wei, Shina; Wei, Jingguang; Qin, Qiwei

    2015-02-01

    Interferon regulatory factor 3 (IRF3) is an important transcription factor which regulates the expression of interferon (IFN) and IFN-stimulated genes (ISGs) following virus recognition. In this study, a novel IRF3 gene was cloned from grouper Epinephelus coioides (EcIRF3) and its effects against Singapore grouper iridovirus (SGIV) and red spotted grouper nervous necrosis virus (RGNNV) was investigated. The full-length of EcIRF3 cDNA was composed of 2513 bp and encoded a polypeptide of 458 amino acids which shared 82% identity with European seabass (Dicentrarchus labrax). EcIRF3 contained three conserved domains including a DNA-binding domain (DBD), an IRF associated domain (IAD) and a serine-rich domain. Expression profile analysis revealed that EcIRF3 was abundant in head kidney, kidney, spleen and gill. Upon different stimuli in vitro, the transcript of EcIRF3 was significantly up-regulated after RGNNV infection or treatment with polyinosin-polycytidylic acid (poly I:C). During SGIV infection, the increase of the EcIRF3 transcription was only detected at the late stage, suggesting that EcIRF3 was differently regulated by different stimuli. Immune fluorescence assay indicated that the fluorescence signal of EcIRF3 was increased significantly after infection with RGNNV or treatment with poly I:C, but moderately at the late stage of SGIV infection. Reporter gene assay showed that EcIRF3 activated zebrafish type I IFN and type III IFN promoter in vitro. The viral gene transcription and virus production of RGNNV were significantly decreased in EcIRF3 overexpressing cells. However, the ectopic expression of EcIRF3 did not affect the gene transcription and virus production of SGIV. Moreover, the mRNA expression levels of type I IFN and IFN-inducible genes (MxI, ISG15 and ISG56) were increased in RGNNV infected EcIRF3 overexpressing cells compared to empty vector transfected cells. Together, our results demonstrated that IFN immune response mediated by grouper IRF3 was

  18. The Effect of Lupinus albus on Growth Performance, Body Composition and Satiety Hormones of Male Pigs Immunized against Gonadotrophin Releasing Factor

    Science.gov (United States)

    Moore, Karen; Mullan, Bruce; Kim, Jae Cheol; Dunshea, Frank

    2017-01-01

    Simple Summary Pigs immunized against gonadotrophin releasing factor (immunocastrates; IC males) have an increased feed intake, growth rate, back fat and fat deposition compared to entire males. A previous experiment found that Lupinus albus L. (albus lupins) has the potential to reduce feed intake and fat deposition in IC males. The current experiment aimed to develop a dietary management strategy using albus lupins for either 14 or 28 days pre-slaughter to reduce the increase in feed intake and subsequent increase in carcass fatness in IC males. Abstract Two hundred and ninety four pigs were used with the aim to develop a dietary management strategy using Lupinus albus L. (albus lupins) to reduce the increase in feed intake and subsequent increase in carcass fatness in pigs immunized against gonadotrophin releasing factor (immunocastrates; IC males) and entire male pigs in the late finishing stage. From day (d) 0 to 28, IC males fed the control diet grew faster (p = 0.009) than entire males fed the control diet but there was no difference in growth rate between sexes for pigs fed albus lupins for 14 days pre-slaughter (Albus 14) or pigs fed albus lupins for 28 days pre-slaughter (Albus 28). From d 15 to 28, IC males receiving the Albus 14 diet grew more slowly (p < 0.001) than entire males receiving the Albus 14 diet. From d 15 to 28 (p < 0.001), IC males fed the control diet ate more feed than entire males fed the control diet, although there was no difference between sexes in feed intake of the Albus 14 and Albus 28 diet. Immunocastrates had a lower backfat when fed either Albus 14 or Albus 28 compared to the control diet, although there was no difference between diets for entire males. There was also a trend for pigs on the Albus 14 and Albus 28 diets to have a higher lean deposition (p = 0.055) and a lower fat deposition (p = 0.056) compared to the pigs on the control diet. Pigs fed the Albus 28 diet had a lower plasma ghrelin concentration compared to pigs

  19. Platelet-Derived Growth Factor-BB Protects Mesenchymal Stem Cells (MSCs) Derived From Immune Thrombocytopenia Patients Against Apoptosis and Senescence and Maintains MSC-Mediated Immunosuppression.

    Science.gov (United States)

    Zhang, Jia-Min; Feng, Fei-Er; Wang, Qian-Ming; Zhu, Xiao-Lu; Fu, Hai-Xia; Xu, Lan-Ping; Liu, Kai-Yan; Huang, Xiao-Jun; Zhang, Xiao-Hui

    2016-12-01

    : Immune thrombocytopenia (ITP) is characterized by platelet destruction and megakaryocyte dysfunction. Mesenchymal stem cells (MSCs) from ITP patients (MSC-ITP) do not exhibit conventional proliferative abilities and thus exhibit defects in immunoregulation, suggesting that MSC impairment might be a mechanism involved in ITP. Platelet-derived growth factor (PDGF) improves growth and survival in various cell types. Moreover, PDGF promotes MSC proliferation. The aim of the present study was to analyze the effects of PDGF-BB on MSC-ITP. We showed that MSC-ITP expanded more slowly and appeared flattened and larger. MSC-ITP exhibited increased apoptosis and senescence compared with controls. Both the intrinsic and extrinsic pathways account for the enhanced apoptosis. P53 and p21 expression were upregulated in MSC-ITP, but inhibition of p53 with pifithrin-α markedly inhibited apoptosis and senescence. Furthermore, MSCs from ITP patients showed a lower capacity for inhibiting the proliferation of activated T cells inducing regulatory T cells (Tregs) and suppressing the synthesis of anti-glycoprotein (GP)IIb-IIIa antibodies. PDGF-BB treatment significantly decreased the expression of p53 and p21 and increased survivin expression in MSC-ITP. In addition, the apoptotic rate and number of senescent cells in ITP MSCs were reduced. Their impaired ability for inhibiting activated T cells, inducing Tregs, and suppressing the synthesis of anti-GPIIb-IIIa antibodies was restored after PDGF-BB treatment. In conclusion, we have demonstrated that PDGF-BB protects MSCs derived from ITP patients against apoptosis, senescence, and immunomodulatory defects. This protective effect of PDGF-BB is likely mediated via the p53/p21 pathway, thus potentially providing a new therapeutic approach for ITP. Immune thrombocytopenia (ITP) is characterized by platelet destruction and megakaryocyte dysfunction. Platelet-derived growth factor (PDGF) improves growth and survival in various cell types

  20. Purification and initial characterization of the 71-kilodalton rat heat-shock protein and its cognate as fatty acid binding proteins.

    Science.gov (United States)

    Guidon, P T; Hightower, L E

    1986-06-03

    The major rat heat-shock (stress) protein and its cognate were purified to electrophoretic homogeneity from livers of heat-shocked rats. Both proteins exhibited similar behavior on a variety of column chromatography matrices but were separable by preparative isoelectric focusing under nondenaturing conditions by virtue of a 0.2 pH unit difference in isoelectric point. Both purified proteins had similar physical properties, suggesting the possibility that they may have similar biological functions as well. Both proteins were homodimers under nondissociative conditions (Mr 150 000) with isoelectric points of 5.0 (cognate) and 5.2 (major stress protein). After denaturation, both proteins had an increase in isoelectric point of 0.6 pH unit, and the resulting polypeptide chains had apparent molecular weights of 73 000 (cognate) and 71 000 (major stress protein). Similarities in the electrophoretic properties of these two proteins and serum albumin, which also undergoes a large basic shift in isoelectric point due to loss of fatty acids and conformational changes accompanying denaturation, prompted us to search for lipids associated with the purified 71-kilodalton stress protein and its cognate. Thin-layer chromatography of chloroform/methanol extracts of these two proteins revealed nonesterified fatty acids bound to both proteins. Palmitic acid, stearic acid, and a small amount of myristic acid were identified by gas chromatography/mass spectroscopy. Both proteins contained approximately four molecules of fatty acid per dimer with palmitate and stearate present in a one to one molar ratio. Possible roles of the major stress protein and its cognate as fatty acid associated proteins in cellular responses to stress are discussed.

  1. Transcription factors regulating B cell fate in the germinal centre.

    Science.gov (United States)

    Recaldin, T; Fear, D J

    2016-01-01

    Diversification of the antibody repertoire is essential for the normal operation of the vertebrate adaptive immune system. Following antigen encounter, B cells are activated, proliferate rapidly and undergo two diversification events; somatic hypermutation (followed by selection), which enhances the affinity of the antibody for its cognate antigen, and class-switch recombination, which alters the effector functions of the antibody to adapt the response to the challenge faced. B cells must then differentiate into antibody-secreting plasma cells or long-lived memory B cells. These activities take place in specialized immunological environments called germinal centres, usually located in the secondary lymphoid organs. To complete the germinal centre activities successfully, a B cell adopts a transcriptional programme that allows it to migrate to specific sites within the germinal centre, proliferate, modify its DNA recombination and repair pathways, alter its apoptotic potential and finally undergo terminal differentiation. To co-ordinate these processes, B cells employ a number of 'master regulator' transcription factors which mediate wholesale transcriptomic changes. These master transcription factors are mutually antagonistic and form a complex regulatory network to maintain distinct gene expression programs. Within this network, multiple points of positive and negative feedback ensure the expression of the 'master regulators', augmented by a number of 'secondary' factors that reinforce these networks and sense the progress of the immune response. In this review we will discuss the different activities B cells must undertake to mount a successful T cell-dependent immune response and describe how a regulatory network of transcription factors controls these processes.

  2. High Vaccination Coverage among Children during Influenza A(H1N1pdm09 as a Potential Factor of Herd Immunity

    Directory of Open Access Journals (Sweden)

    Toshihiko Matsuoka

    2016-10-01

    Full Text Available The objective of this study was to identify factors related to the expansion of infection and prevention of influenza A(H1N1pdm09. A retrospective non-randomized cohort study (from June 2009 to May 2010 on influenza A(H1N1pdm09 was conducted in a sample of residents from Hiroshima Prefecture, Japan. The cumulative incidence of the influenza A(H1N1pdm09 and the pandemic vaccine effectiveness (VE were estimated. The response rate was 53.5% (178,669/333,892. Overall, the odds ratio of non-vaccinated group to vaccinated group for cumulative incidence of influenza A(H1N1pdm09 was 2.18 (95% confidence interval (CI: 2.13–2.23 and the VE was 43.9% (CI: 42.8–44.9. The expansion of infection, indicating the power of transmission from infected person to susceptible person, was high in the 7–15 years age groups in each area. In conclusion, results from this survey suggested that schoolchildren-based vaccination rate participates in determining the level of herd immunity to influenza and children might be the drivers of influenza transmission. For future pandemic preparedness, vaccination of schoolchildren may help to prevent disease transmission during influenza outbreak.

  3. Nuclear Factor of Activated T Cells and Cytokines Gene Expression of the T Cells in AIDS Patients with Immune Reconstitution Inflammatory Syndrome during Highly Active Antiretroviral Therapy

    Science.gov (United States)

    Chen, Heling; Xie, Yirui; Su, Junwei; Huang, Ying; Xu, Lijun; Yin, Michael; Zhou, Qihui

    2017-01-01

    Background. The etiology of immune reconstitution inflammatory syndrome (IRIS) in AIDS patients after the initiation of HAART remains unknown. Several researches indicated that the development of IRIS is associated with the production and variation of cytokines, whose gene expression are closely related to the Ca2+/CN-nuclear factor of activated T cells (NFAT) pathway. Methods. We studied the expression of NFAT isoforms and their major target cytokines genes in peripheral blood CD3+ T cells of subjects through fluorescence quantitative PCR and explored the expression changes of these genes before and after HAART. Results. After the initiation of HARRT, NFAT1, IL-6, and IL-8 gene expression showed a reversal trend in the CD3+ T cells of the IRIS group and changed from low expression before HARRT to high expression after HARRT. In particular, the relative gene expression of NFAT1 was markedly higher compared with the other three isoforms. The IRIS group also showed higher NFAT4, NFAT2, NFAT1, IL-1β, IL-10, IL-2, IL-18, and TNF-α gene expression than the non-IRIS group. Conclusion. This study suggested that high expression levels of IL-2, IL-6, IL-8, TNF-α, IL-1β, IL-10, IL-12, and IL-18 can predict the risk of IRIS. The increased expression of NFAT1 and NFAT4 may promote the expression of cytokines, such as IL-6, IL-8, and TNF-α, which may promote the occurrence of IRIS.

  4. RESPONSE OF MONONUCLEAR CELLS TO CANCER-ASSOCIATED ANTIGENS, HUMORAL FACTORS OF IMMUNITY, AND PATHOHISTOLOGICAL FINDINGS IN WOMEN WITH GENITAL MALIGNANCIES CERVICAL EPITHELIAL DYSPLASIA

    Directory of Open Access Journals (Sweden)

    A. I. Autenshlus

    2007-01-01

    Full Text Available Abstract. In vitro response of blood mononuclear cells to cancer-associated antigens was studied in women with genital pathology, and these results were compared with serum levels of pro- and anti-inflammatory factors of immunity, like as with histological features of genital cancer and cervical epithelial dysplasia. In vitro cellular response was regarded as positive, if relative amounts of CD8-positive lymphocytes increased by > 15% following incubation of blood mononuclears with cancer-associated antigens. Positive reaction and elevated serum levels of anti-TNFα and anti-IFNγ antibodies were associated with lesser malignancy of tumor, as proven by histological findings in the women with genital cancer. A positive cellular reaction was associated with increased serum levels of IFNγ and anti-TNFα in women with grade II–III cervical epithelial dysplasia. It is concluded about potential applicability of testing mononuclears with fetal proteins, to determine a grade of malignancy for the female genital tumors, as well as a degree of regenerative disturbances of cervical epithelium.

  5. High Vaccination Coverage among Children during Influenza A(H1N1)pdm09 as a Potential Factor of Herd Immunity

    Science.gov (United States)

    Matsuoka, Toshihiko; Sato, Tomoki; Akita, Tomoyuki; Yanagida, Jiturou; Ohge, Hiroki; Kuwabara, Masao; Tanaka, Junko

    2016-01-01

    The objective of this study was to identify factors related to the expansion of infection and prevention of influenza A(H1N1)pdm09. A retrospective non-randomized cohort study (from June 2009 to May 2010) on influenza A(H1N1)pdm09 was conducted in a sample of residents from Hiroshima Prefecture, Japan. The cumulative incidence of the influenza A(H1N1)pdm09 and the pandemic vaccine effectiveness (VE) were estimated. The response rate was 53.5% (178,669/333,892). Overall, the odds ratio of non-vaccinated group to vaccinated group for cumulative incidence of influenza A(H1N1)pdm09 was 2.18 (95% confidence interval (CI): 2.13–2.23) and the VE was 43.9% (CI: 42.8–44.9). The expansion of infection, indicating the power of transmission from infected person to susceptible person, was high in the 7–15 years age groups in each area. In conclusion, results from this survey suggested that schoolchildren-based vaccination rate participates in determining the level of herd immunity to influenza and children might be the drivers of influenza transmission. For future pandemic preparedness, vaccination of schoolchildren may help to prevent disease transmission during influenza outbreak. PMID:27763532

  6. Early eradication of factor VIII inhibitor in patients with congenital hemophilia A by immune tolerance induction with a high dose of immunoglobulin.

    Science.gov (United States)

    Mizoguchi, Yoko; Furue, Aya; Kagawa, Reiko; Chijimatsu, Ikue; Tomioka, Keita; Shimomura, Maiko; Imanaka, Yusuke; Nishimura, Shiho; Saito, Satoshi; Miki, Mizuka; Ono, Atsushi; Konishi, Nakao; Kawaguchi, Hiroshi; Kobayashi, Masao

    2016-04-01

    The production of factor VIII (FVIII) inhibitory antibodies is a serious problem in patients with hemophilia A. Immune tolerance induction (ITI) is the only strategy proven to eradicate persistent inhibitors and has been shown to be successful in 70 % of patients with hemophilia A. However, a minority of hemophilia patients present life-long inhibitors. To eliminate such inhibitors, we designed an intravenous immunoglobulin (IVIG) strategy in combination with high dose recombinant FVIII for ITI in hemophilia A children with inhibitors. Four previously untreated patients produced inhibitors within 16 exposures to FVIII. The peak inhibitor titers in these patients ranged from 3 to 14 BU/mL. The patients received ITI combined with IVIG within 1.5 months after the inhibitors were detected. All patients showed a negative titer for inhibitors by 28 days, with no anamnestic responses. The recovery of FVIII in the plasma concentration was normalized within three months after initiation of ITI. An additional course of IVIG administration led to induction of complete tolerance by 20 months after initiation of ITI therapy in all patients. ITI treatment with high-dose FVIII combined with IVIG may be effective for the early elimination of inhibitors.

  7. IL–18 AND IMMUNITY

    Directory of Open Access Journals (Sweden)

    E. V. Yakushenko

    2005-01-01

    Full Text Available Abstract. Interleukin–18 is one of the main cytokines, inducing production of IFNg. It is the important factor of anti–infectious and anti–tumor immunity. The review represent molecular–genetic and biochemical characteristics of IL–18. The data about producers, the structure of the receptor and of IL–18 binding protein, as well as signal transduction in the cell are considered. Besides that, the main immune effects of IL–18 are discussed. (Med. Immunol., 2005, vol.7, № 4, pp 355–364

  8. Red Seaweeds Sarcodiotheca gaudichaudii and Chondrus crispus down Regulate Virulence Factors of Salmonella Enteritidis and Induce Immune Responses in Caenorhabditis elegans

    Science.gov (United States)

    Kulshreshtha, Garima; Borza, Tudor; Rathgeber, Bruce; Stratton, Glenn S.; Thomas, Nikhil A.; Critchley, Alan; Hafting, Jeff; Prithiviraj, Balakrishnan

    2016-01-01

    Red seaweeds are a rich source of unique bioactive compounds and secondary metabolites that are known to improve human and animal health. S. Enteritidis is a broad range host pathogen, which contaminates chicken and poultry products that end into the human food chain. Worldwide, Salmonella outbreaks have become an important economic and public health concern. Moreover, the development of resistance in Salmonella serovars toward multiple drugs highlights the need for alternative control strategies. This study evaluated the antimicrobial property of red seaweeds extracts against Salmonella Enteritidis using the Caenorhabditis elegans infection model. Six red seaweed species were tested for their antimicrobial activity against S. Enteritidis and two, Sarcodiotheca gaudichaudii (SG) and Chondrus crispus (CC), were found to exhibit such properties. Spread plate assay revealed that SG and CC (1%, w/v) significantly reduced the growth of S. Enteritidis. Seaweed water extracts (SWE) of SG and CC, at concentrations from 0.4 to 2 mg/ml, significantly reduced the growth of S. Enteritidis (log CFU 4.5–5.3 and log 5.7–6.0, respectively). However, methanolic extracts of CC and SG did not affect the growth of S. Enteritidis. Addition of SWE (0.2 mg/ml, CC and SG) significantly decreased biofilm formation and reduced the motility of S. Enteritidis. Quantitative real-time PCR analyses showed that SWE (CC and SG) suppressed the expression of quorum sensing gene sdiA and of Salmonella Pathogenesis Island-1 (SPI-1) associated genes sipA and invF, indicating that SWE might reduce the invasion of S. Enteritidis in the host by attenuating virulence factors. Furthermore, CC and SG water extracts significantly improved the survival of infected C. elegans by impairing the ability of S. Enteritidis to colonize the digestive tract of the nematode and by enhancing the expression of C. elegans immune responsive genes. As the innate immune response pathways of C. elegans and mammals show a

  9. HTLV-1 bZIP Factor Impairs Anti-viral Immunity by Inducing Co-inhibitory Molecule, T Cell Immunoglobulin and ITIM Domain (TIGIT.

    Directory of Open Access Journals (Sweden)

    Keiko Yasuma

    2016-01-01

    Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 infects CD4+ T cells and induces proliferation of infected cells in vivo, which leads to the onset of adult T-cell leukemia (ATL in some infected individuals. The HTLV-1 bZIP factor (HBZ gene, which is encoded in the minus strand of HTLV-1, plays critical roles in pathogenesis. In this study, RNA-seq and ChIP-seq analyses using HBZ transduced T cells revealed that HBZ upregulates the expression and promoter acetylation levels of a co-inhibitory molecule, T cell immunoglobulin and ITIM domain (TIGIT, in addition to those of regulatory T cells related genes, Foxp3 and Ccr4. TIGIT was expressed on CD4+ T cells from HBZ-transgenic (HBZ-Tg mice, and on ATL cells and HTLV-1 infected CD4+ T cells of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP in vivo. Expression of Blimp1 and IL-10 was upregulated in TIGIT+CD4+ cells of HBZ-Tg mice compared with TIGIT-CD4+ T cells, suggesting the correlation between TIGIT expression and IL-10 production. When CD4+ T cells from HBZ-Tg mice were stimulated with TIGIT's ligand, CD155, their production of the inhibitory cytokine IL-10 was enhanced. Furthermore, dendritic cells from HBZ-Tg mice produced high levels of IL-10 after stimulation. These data suggest that HBZ alters immune system to suppressive state via TIGIT and IL-10. Importantly, TIGIT suppressed T-cell responses to another HTLV-1 virus protein, Tax, in vitro. Blocking of TIGIT and PD-1 slightly increased anti-Tax T-cell activity in some HAM/TSP patients. These results suggest that HBZ-induced TIGIT on HTLV-1 infected cells impairs T-cell responses to viral antigens. This study shows that HBZ-induced TIGIT plays a pivotal role in attenuating host immune responses and shaping a microenvironment favorable to HTLV-1.

  10. Candida Immunity

    Directory of Open Access Journals (Sweden)

    Julian R. Naglik

    2014-01-01

    Full Text Available The human pathogenic fungus Candida albicans is the predominant cause of both superficial and invasive forms of candidiasis. C. albicans primarily infects immunocompromised individuals as a result of either immunodeficiency or intervention therapy, which highlights the importance of host immune defences in preventing fungal infections. The host defence system utilises a vast communication network of cells, proteins, and chemical signals distributed in blood and tissues, which constitute innate and adaptive immunity. Over the last decade the identity of many key molecules mediating host defence against C. albicans has been identified. This review will discuss how the host recognises this fungus, the events induced by fungal cells, and the host innate and adaptive immune defences that ultimately resolve C. albicans infections during health.

  11. Effects of RNA interference targeting transforming growth factor-beta 1 on immune hepatic ifbrosis induced by Concanavalin A in mice

    Institute of Scientific and Technical Information of China (English)

    Wei Xu; Lu-Wen Wang; Jin-Zhi Shi; Zuo-Jiong Gong

    2009-01-01

    BACKGROUND: Previous studies have shown that transforming growth factor-beta 1 (TGF-β1) is the most potent means of stimulating liver ifbrogenesis by myoifbroblast-like cells derived from hepatic stellate cells. Thus, TGF-β1 could be a target for treating hepatic ifbrosis. This study aimed to investigate the inhibitory effects of speciifc TGF-β1 small interference RNA (siRNA) on immune hepatic ifbrosis induced by Concanavalin A (Con A) in mice. METHODS: Three short hairpin RNAs targeting different positions of TGF-β1 were designed and cloned to the plasmid pGenesil-1 to obtain three recombinant expression vectors (pGenesil-TGF-β1-m1, pGenesil-TGF-β1-m2 and pGenesil-TGF-β1-m3). Thirty male Kunming mice were randomly divided into 6 groups: normal, model, control, and three treatment groups. The immune hepatic ifbrosis models were constructed by injecting Con A via the tail vein at 8 mg/kg per week for 6 weeks. At weeks 2, 4 and 6, pGenesil-TGF-β1-m1, pGenesil-TGF-β1-m2 or pGenesil-TGF-β1-m3 was injected by a hydrodynamics-based transfection method via the tail vein at 0.8 ml/10 g within 24 hours after injection of Con A in each of the three treatment groups. The mice in the control group were injected with control plasmid pGenesil-HK at the same dose. All mice were sacriifced at week 7. The levels of hydroxyproline in liver tissue were determined by biochemistry. Liver histopathology was assessed by Van Gieson staining. The expression levels and localization of TGF-β1, Smad3, and Smad7 in liver tissue were detected by immunohistochemistry. The expression of TGF-β1, Smad3, Smad7 and alpha-smooth muscle actin (α-SMA) mRNAs in the liver were assessed by semi-quantitative RT-PCR.RESULTS: The levels of hydroxyproline in the liver tissue of the treatment groups were lower than those of the model group (P0.05), but the inhibitory effect of pGenesil-TGF-β1-m1 was the highest among the treatment groups. CONCLUSIONS: Speciifc siRNA targeting of TGF-β1

  12. Early nutrition and immunity - progress and perspectives

    DEFF Research Database (Denmark)

    Calder, PC; Krauss-Etschmann, S; de Jong, EC

    2006-01-01

    and factors affecting the development of atopic disease; factors influencing the maturation of dendritic cells and the development of regulatory T cells; the influence of gut microflora on immunity, allergic sensitization and infectious disease; the role of nutrition in preventing necrotizing enterocolitis...... immune systems. The introduction of formula and of solid foods exposes the infant to novel food antigens and also affects the gut flora. Nutrition may be the source of antigens to which the immune system must become tolerant, provide factors, including nutrients, that themselves might modulate immune...... maturation and responses, and provide factors that influence intestinal flora, which in turn will affect antigen exposure, immune maturation and immune responses. Through these mechanisms it is possible that nutrition early in life might affect later immune competence, the ability to mount an appropriate...

  13. Regulation of dynamic polarity switching in bacteria by a Ras-like G-protein and its cognate GAP.

    Science.gov (United States)

    Leonardy, Simone; Miertzschke, Mandy; Bulyha, Iryna; Sperling, Eva; Wittinghofer, Alfred; Søgaard-Andersen, Lotte

    2010-07-21

    The rod-shaped cells of the bacterium Myxococcus xanthus move uni-directionally and occasionally undergo reversals during which the leading/lagging polarity axis is inverted. Cellular reversals depend on pole-to-pole relocation of motility proteins that localize to the cell poles between reversals. We show that MglA is a Ras-like G-protein and acts as a nucleotide-dependent molecular switch to regulate motility and that MglB represents a novel GTPase-activating protein (GAP) family and is the cognate GAP of MglA. Between reversals, MglA/GTP is restricted to the leading and MglB to the lagging pole defining the leading/lagging polarity axis. For reversals, the Frz chemosensory system induces the relocation of MglA/GTP to the lagging pole causing an inversion of the leading/lagging polarity axis. MglA/GTP stimulates motility by establishing correct polarity of motility proteins between reversals and reversals by inducing their pole-to-pole relocation. Thus, the function of Ras-like G-proteins and their GAPs in regulating cell polarity is found not only in eukaryotes, but also conserved in bacteria.

  14. Modulation of the chaperone heat shock cognate 70 by embryonic (pro)insulin correlates with prevention of apoptosis

    Science.gov (United States)

    de la Rosa, Enrique J.; Vega-Núñez, Elena; Morales, Aixa V.; Serna, José; Rubio, Eva; de Pablo, Flora

    1998-01-01

    Insights have emerged concerning insulin function during development, from the finding that apoptosis during chicken embryo neurulation is prevented by prepancreatic (pro)insulin. While characterizing the molecules involved in this survival effect of insulin, we found insulin-dependent regulation of the molecular chaperone heat shock cognate 70 kDa (Hsc70), whose cloning in chicken is reported here. This chaperone, generally considered constitutively expressed, showed regulation of its mRNA and protein levels in unstressed embryos during early development. More important, Hsc70 levels were found to depend on endogenous (pro)insulin, as shown by using antisense oligodeoxynucleotides against (pro)insulin mRNA in cultured neurulating embryos. Further, in the cultured embryos, apoptosis affected mainly cells with the lowest level of Hsc70, as shown by simultaneous Hsc70 immunostaining and terminal deoxynucleotidyltransferase-mediated UTP nick end labeling. These results argue in favor of Hsc70 involvement, modulated by embryonic (pro)insulin, in the prevention of apoptosis during early development and suggest a role for a molecular chaperone in normal embryogenesis. PMID:9707581

  15. Structure of the Mecl Repressor from Staphylococcus aureus in Complex with the Cognate DNA Operator of mec

    Energy Technology Data Exchange (ETDEWEB)

    Safo,M.; Ko, T.; Musayev, F.; Zhao, Q.; Wang, A.; Archer, G.

    2006-01-01

    The dimeric repressor MecI regulates the mecA gene that encodes the penicillin-binding protein PBP-2a in methicillin-resistant Staphylococcus aureus (MRSA). MecI is similar to BlaI, the repressor for the blaZ gene of {beta}-lactamase. MecI and BlaI can bind to both operator DNA sequences. The crystal structure of MecI in complex with the 32 base-pair cognate DNA of mec was determined to 3.8 Angstroms resolution. MecI is a homodimer and each monomer consists of a compact N-terminal winged-helix domain, which binds to DNA, and a loosely packed C-terminal helical domain, which intertwines with its counter-monomer. The crystal contains horizontal layers of virtual DNA double helices extending in three directions, which are separated by perpendicular DNA segments. Each DNA segment is bound to two MecI dimers. Similar to the BlaI-mec complex, but unlike the MecI-bla complex, the MecI repressors bind to both sides of the mec DNA dyad that contains four conserved sequences of TACA/TGTA. The results confirm the up-and-down binding to the mec operator, which may account for cooperative effect of the repressor.

  16. Structure of the MecI repressor from Staphylococcus aureus in complex with the cognate DNA operator of mec

    Energy Technology Data Exchange (ETDEWEB)

    Safo, Martin K., E-mail: msafo@vcu.edu [Department of Medicinal Chemistry, School of Pharmacy and Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia 23298 (United States); Ko, Tzu-Ping [Institute of Biological Chemistry, Academia Sinica, Taipei 11529,Taiwan (China); Musayev, Faik N. [Department of Medicinal Chemistry, School of Pharmacy and Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia 23298 (United States); Zhao, Qixun [Department of Medicine and Department of Microbiology/Immunology, Virginia Commonwealth University, Richmond, Virginia 23298 (United States); Wang, Andrew H.-J. [Institute of Biological Chemistry, Academia Sinica, Taipei 11529,Taiwan (China); Archer, Gordon L. [Department of Medicine and Department of Microbiology/Immunology, Virginia Commonwealth University, Richmond, Virginia 23298 (United States); Department of Medicinal Chemistry, School of Pharmacy and Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia 23298 (United States)

    2006-04-01

    The up-and-down binding of dimeric MecI to mecA dyad DNA may account for the cooperative effect of the repressor. The dimeric repressor MecI regulates the mecA gene that encodes the penicillin-binding protein PBP-2a in methicillin-resistant Staphylococcus aureus (MRSA). MecI is similar to BlaI, the repressor for the blaZ gene of β-lactamase. MecI and BlaI can bind to both operator DNA sequences. The crystal structure of MecI in complex with the 32 base-pair cognate DNA of mec was determined to 3.8 Å resolution. MecI is a homodimer and each monomer consists of a compact N-terminal winged-helix domain, which binds to DNA, and a loosely packed C-terminal helical domain, which intertwines with its counter-monomer. The crystal contains horizontal layers of virtual DNA double helices extending in three directions, which are separated by perpendicular DNA segments. Each DNA segment is bound to two MecI dimers. Similar to the BlaI–mec complex, but unlike the MecI–bla complex, the MecI repressors bind to both sides of the mec DNA dyad that contains four conserved sequences of TACA/TGTA. The results confirm the up-and-down binding to the mec operator, which may account for cooperative effect of the repressor.

  17. Crystal Structure of the FimD Usher Bound to its Cognate FimC-FimH Substrate

    Energy Technology Data Exchange (ETDEWEB)

    G Phan; H Remaut; T Wang; W Allen; K Pirker; A Lebedev; N Henderson; S Geibel; E Volkan; et al.

    2011-12-31

    Type 1 pili are the archetypal representative of a widespread class of adhesive multisubunit fibres in Gram-negative bacteria. During pilus assembly, subunits dock as chaperone-bound complexes to an usher, which catalyses their polymerization and mediates pilus translocation across the outer membrane. Here we report the crystal structure of the full-length FimD usher bound to the FimC-FimH chaperone-adhesin complex and that of the unbound form of the FimD translocation domain. The FimD-FimC-FimH structure shows FimH inserted inside the FimD 24-stranded {beta}-barrel translocation channel. FimC-FimH is held in place through interactions with the two carboxy-terminal periplasmic domains of FimD, a binding mode confirmed in solution by electron paramagnetic resonance spectroscopy. To accommodate FimH, the usher plug domain is displaced from the barrel lumen to the periplasm, concomitant with a marked conformational change in the {beta}-barrel. The amino-terminal domain of FimD is observed in an ideal position to catalyse incorporation of a newly recruited chaperone-subunit complex. The FimD-FimC-FimH structure provides unique insights into the pilus subunit incorporation cycle, and captures the first view of a protein transporter in the act of secreting its cognate substrate.

  18. A MUB E2 structure reveals E1 selectivity between cognate ubiquitin E2s in eukaryotes

    Science.gov (United States)

    Lu, Xiaolong; Malley, Konstantin R.; Brenner, Caitlin C.; Koroleva, Olga; Korolev, Sergey; Downes, Brian P.

    2016-08-01

    Ubiquitin (Ub) is a protein modifier that controls processes ranging from protein degradation to endocytosis, but early-acting regulators of the three-enzyme ubiquitylation cascade are unknown. Here we report that the prenylated membrane-anchored ubiquitin-fold protein (MUB) is an early-acting regulator of subfamily-specific E2 activation. An AtMUB3:AtUBC8 co-crystal structure defines how MUBs inhibit E2~Ub formation using a combination of E2 backside binding and a MUB-unique lap-bar loop to block E1 access. Since MUBs tether Arabidopsis group VI E2 enzymes (related to HsUbe2D and ScUbc4/5) to the plasma membrane, and inhibit E2 activation at physiological concentrations, they should function as potent plasma membrane localized regulators of Ub chain synthesis in eukaryotes. Our findings define a biochemical function for MUB, a family of highly conserved Ub-fold proteins, and provide an example of selective activation between cognate Ub E2s, previously thought to be constitutively activated by E1s.

  19. Heat shock cognate protein 70 contributes to Brucella invasion into trophoblast giant cells that cause infectious abortion

    Directory of Open Access Journals (Sweden)

    Furuoka Hidefumi

    2008-12-01

    Full Text Available Abstract Background The cell tropism of Brucella abortus, a causative agent of brucellosis and facultative intracellular pathogen, in the placenta is thought to be a key event of infectious abortion, although the molecular mechanism for this is largely unknown. There is a higher degree of bacterial colonization in the placenta than in other organs and many bacteria are detected in trophoblast giant (TG cells in the placenta. In the present study, we investigated mechanism of B. abortus invasion into TG cells. Results We observed internalization and intracellular growth of B. abortus in cultured TG cells. A monoclonal antibody that inhibits bacterial internalization was isolated and this reacted with heat shock cognate protein 70 (Hsc70. Depletion and over expression of Hsc70 in TG cells inhibited and promoted bacterial internalization, respectively. IFN-γ receptor was expressed in TG cells and IFN-γ treatment enhanced the uptake of bacteria by TG cells. Administering the anti-Hsc70 antibody to pregnant mice served to prevent infectious abortion. Conclusion B. abortus infection of TG cells in placenta is mediated by Hsc70, and that such infection leads to infectious abortion.

  20. Intercellular adhesion molecule 1 serves as a primary cognate receptor for the Type IV pilus of nontypeable Haemophilus influenzae.

    Science.gov (United States)

    Novotny, Laura A; Bakaletz, Lauren O

    2016-08-01

    Nontypeable Haemophilus influenzae (NTHI) utilizes the Type IV pilus (Tfp) to adhere to respiratory tract epithelial cells thus colonizing its human host; however, the host cell receptor to which this adhesive protein binds is unknown. From a panel of receptors engaged by Tfp expressed by other bacterial species, we showed that the majority subunit of NTHI Tfp, PilA, bound to intercellular adhesion molecule 1 (ICAM1) and that this interaction was both specific and of high affinity. Further, Tfp-expressing NTHI inoculated on to polarized respiratory tract epithelial cells that expressed ICAM1 were significantly more adherent compared to Tfp-deficient NTHI or NTHI inoculated on to epithelial cells to which ICAM1 gene expression was silenced. Moreover, pre-incubation of epithelial cells with recombinant soluble PilA (rsPilA) blocked adherence of NTHI, an outcome that was abrogated by admixing rsPilA with ICAM1 prior to application on to the target cells. Epithelial cells infected with adenovirus or respiratory syncytial virus showed increased expression of ICAM1; this outcome supported augmented adherence of Tfp-expressing NTHI. Collectively, these data revealed the cognate receptor for NTHI Tfp as ICAM1 and promote continued development of a Tfp-targeted vaccine for NTHI-induced diseases of the airway wherein upper respiratory tract viruses play a key predisposing role.

  1. Maternal immune stimulation reduces both placental morphologic damage and down-regulated placental growth-factor and cell cycle gene expression caused by urethane: are these events related to reduced teratogenesis?

    Science.gov (United States)

    Sharova, L V; Sharov, A A; Sura, P; Gogal, R M; Smith, B J; Holladay, S D

    2003-07-01

    Activation of the maternal immune system in mice decreased cleft palate caused by the chemical teratogen, urethane. Direct and indirect mechanisms for this phenomenon have been suggested, including maternal macrophages that cross the placenta to find and eliminate pre-teratogenic cells, or maternal immune proteins (cytokines) that cross placenta to alleviate or partially alleviate toxicant-mediated effects in the developing fetus. A third mechanism to explain improved fetal developmental outcome in teratogen-challenged pregnant mice might involve beneficial effects of immune stimulation on the placenta. In the present experiments, urethane treatment altered placental morphology and impaired placental function, the latter indicated by down-regulated activity of cell cycle genes and of genes encoding cytokines and growth factors. Maternal immune stimulation with either Freund's complete adjuvant (FCA) or interferon-gamma (IFNgamma) reduced morphologic damage to the placenta caused by urethane and normalized expression of several genes that were down-regulated by urethane. Urethane treatment also shifted placental cytokine gene expression toward a T cell helper 1 (Th1) profile, while immunostimulation tended to restore a Th2 profile that may be more beneficial to pregnancy and fetal development. These data suggest that the beneficial effects of maternal immune stimulation on fetal development in teratogen-exposed mice may, in part, result from improved placental structure and function.

  2. Reduced interleukin-4 receptor α expression on CD8+ T cells correlates with higher quality anti-viral immunity.

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    Danushka K Wijesundara

    Full Text Available With the hope of understanding how interleukin (IL-4 and IL-13 modulated quality of anti-viral CD8(+ T cells, we evaluated the expression of receptors for these cytokines following a range of viral infections (e.g. pox viruses and influenza virus. Results clearly indicated that unlike other IL-4/IL-13 receptor subunits, IL-4 receptor α (IL-4Rα was significantly down-regulated on anti-viral CD8(+ T cells in a cognate antigen dependent manner. The infection of gene knockout mice and wild-type (WT mice with vaccinia virus (VV or VV expressing IL-4 confirmed that IL-4, IL-13 and signal transducer and activator of transcription 6 (STAT6 were required to increase IL-4Rα expression on CD8(+ T cells, but not interferon (IFN-γ. STAT6 dependent elevation of IL-4Rα expression on CD8(+ T cells was a feature of poor quality anti-viral CD8(+ T cell immunity as measured by the production of IFN-γ and tumor necrosis factor α (TNF-α in response to VV antigen stimulation in vitro. We propose that down-regulation of IL-4Rα, but not the other IL-4/IL-13 receptor subunits, is a mechanism by which CD8(+ T cells reduce responsiveness to IL-4 and IL-13. This can improve the quality of anti-viral CD8(+ T cell immunity. Our findings have important implications in understanding anti-viral CD8(+ T cell immunity and designing effective vaccines against chronic viral infections.

  3. A mRNA and cognate microRNAs localize in the nucleolus.

    Science.gov (United States)

    Reyes-Gutierrez, Pablo; Ritland Politz, Joan C; Pederson, Thoru

    2014-01-01

    We previously discovered that a set of 5 microRNAs are concentrated in the nucleolus of rat myoblasts. We now report that several mRNAs are also localized in the nucleoli of these cells as determined by microarray analysis of RNA from purified nucleoli. Among the most abundant of these nucleolus-localized mRNAs is that encoding insulin-like growth factor 2 (IGF2), a regulator of myoblast proliferation and differentiation. The presence of IGF2 mRNA in nucleoli was confirmed by fluorescence in situ hybridization, and RT-PCR experiments demonstrated that these nucleolar transcripts are spliced, thus arriving from the nucleoplasm. Bioinformatics analysis predicted canonically structured, highly thermodynamically stable interactions between IGF2 mRNA and all 5 of the nucleolus-localized microRNAs. These results raise the possibility that the nucleolus is a staging site for setting up particular mRNA-microRNA interactions prior to export to the cytoplasm.

  4. Immunity to Fish Rhabdoviruses

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    Maureen K. Purcell

    2012-01-01

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

  5. Aging, immunity, and cancer.

    Science.gov (United States)

    Fulop, Tamas; Larbi, Anis; Kotb, Rami; de Angelis, Flavia; Pawelec, Graham

    2011-06-01

    Age is the most important risk factor for tumorigenesis. More than 60% of new cancers and more than 70% of cancer deaths occur in elderly subjects >65 years. The immune system plays an important role in the battle of the host against cancer development. Deleterious alterations occur to the immune response with aging, termed immunosenescence. It is tempting to speculate that this waning immune response contributes to the higher incidence of cancer, but robust data on this important topic are few and far between. This review is devoted to discussing state of the art knowledge on the relationship between immunosenescence and cancer. Emerging understanding of the aging process at the molecular level is viewed from the perspective of this increased tumorigenesis. We also consider some of the most recent means to intervene in the modulation of immunosenescence to increase the ability of the immune system to fight against tumors. Future research will unravel new aspects of the immune response against tumors which will be modulable to decrease the burden of cancer in elderly individuals.

  6. Immunity to fish rhabdoviruses

    Science.gov (United States)

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

    2012-01-01

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

  7. Immune System Toxicity and Immunotoxicity Hazard Identification

    Science.gov (United States)

    Exposure to chemicals may alter immune system health, increasing the risk of infections, allergy and autoimmune diseases. The chapter provides a concise overview of the immune system, host factors that affect immune system heal, and the effects that xenobiotic exposure may have ...

  8. Key Factors for Formulation of Immunization Programs in Animal and Poultry Farms%制定养殖场免疫程序应考虑的主要因素

    Institute of Scientific and Technical Information of China (English)

    尹子静; 刘裕田

    2015-01-01

    Vaccination is an effective way for infectious disease prevention and control, and the quality of immunization programs directly determines the immune effect. In this paper,some key factors for formulation of immunization pro-grams in animal and poultry farms are discussed, including local disease situation,antibody level, vaccination routes, vaccine types and properties,breed sources, feeding management level. The immunization programs must be formu-lated according to the local conditions and the key factors mentioned above.%免疫接种是预防控制传染病的有效方法,免疫程序合理与否直接决定到免疫效果,因此养殖场要按照因地制宜的原则,根据本地的疫病种类、疫病流行情况、抗体水平、免疫途径、疫苗种类与性质、种畜禽来源、饲养管理水平等综合因素,科学制定适合本场的免疫程序。

  9. The Effect of Lupinus albus and Calcium Chloride on Growth Performance, Body Composition, Plasma Biochemistry and Meat Quality of Male Pigs Immunized Against Gonadotrophin Releasing Factor.

    Science.gov (United States)

    Moore, Karen; Mullan, Bruce; Kim, Jae Cheol; Dunshea, Frank

    2016-12-01

    Two hundred and ninety-four pigs were used to assess the effect of two ingredients (Lupinus albus (albus lupins) or a combination of calcium chloride and sodium tri-polyphosphate (mineral salts)) on growth performance, body composition and objective meat quality of pigs immunized against gonadotrophin releasing factor (immunocastrates) and entire male pigs in the late finishing phase. Pigs fed mineral salts ate less feed than those fed the control diet with no effect on growth rate (p > 0.05), backfat (p > 0.05) or fat deposition (p > 0.05). Pigs fed albus lupins had a reduced feed intake (p experiment (p < 0.001), however, feeding albus lupins to immunocastrated males reduced backfat thickness to similar to entire males fed the control diet (p = 0.01). With the exception of the increased muscle pH at 45 minutes post-exsanguination in mineral salts and albus lupins compared with the control diet (p = 0.03) there was no effect of diet on objective pork quality. Pork from IC males had a higher ultimate pH (p < 0.001), was lighter (L*; p = 0.003), more yellow (p = 0.008) and had a higher drip loss (p < 0.001) compared to entire males. Albus lupins show potential in reducing the increase in feed intake and backfat associated with immunocastration. Mineral salts may be useful in situations where a reduction in feed intake and an improvement in feed conversion is desired and reducing fat deposition is not the objective.

  10. Aging and a peripheral immune challenge interact to reduce mature brain-derived neurotrophic factor and activation of TrkB, PLCgamma1, and ERK in hippocampal synaptoneurosomes.

    Science.gov (United States)

    Cortese, Giuseppe P; Barrientos, Ruth M; Maier, Steven F; Patterson, Susan L

    2011-03-16

    For reasons that are not well understood, aging significantly increases brain vulnerability to challenging life events. High-functioning older individuals often experience significant cognitive decline after an inflammatory event such as surgery, infection, or injury. We have modeled this phenomenon in rodents and have previously reported that a peripheral immune challenge (intraperitoneal injection of live Escherichia coli) selectively disrupts consolidation of hippocampus-dependent memory in aged (24-month-old), but not young (3-month-old), F344xBN rats. More recently, we have demonstrated that this infection-evoked memory deficit is mirrored by a selective deficit in long-lasting synaptic plasticity in the hippocampus. Interestingly, these deficits occur in forms of long-term memory and synaptic plasticity known to be strongly dependent on brain-derived neurotrophic factor (BDNF). Here, we begin to test the hypothesis that the combination of aging and an infection might disrupt production or processing of BDNF protein in the hippocampus, decreasing the availability of BDNF for plasticity-related processes at synaptic sites. We find that mature BDNF is markedly reduced in Western blots of hippocampal synaptoneurosomes prepared from aged animals following infection. This reduction is blocked by intra-cisterna magna administration of the anti-inflammatory cytokine IL-1Ra (interleukin 1-specific receptor antagonist). Levels of the pan-neurotrophin receptor p75(NTR) and the BDNF receptor TrkB (tropomyosin receptor kinase B) are not significantly altered in these synaptoneurosomes, but phosphorylation of TrkB and downstream activation of PLCγ1 (phospholipase Cγ1) and ERK (extracellular response kinase) are attenuated-observations consistent with reduced availability of mature BDNF to activate TrkB signaling. These data suggest that inflammation-evoked reductions in BDNF at synapses might contribute to inflammation-evoked disruptions in long-term memory and synaptic

  11. IgM, IgG and IgA rheumatoid factors and circulating immune complexes in patients with AIDS and AIDS-related complex with serological abnormalities.

    Science.gov (United States)

    Procaccia, S; Lazzarin, A; Colucci, A; Gasparini, A; Forcellini, P; Lanzanova, D; Foppa, C U; Novati, R; Zanussi, C

    1987-01-01

    To investigate some humoral aspects which may reflect the involvement of B lymphocytes in the acquired immunodeficiency syndrome (AIDS), we used an enzyme-linked immunoassay (ELISA) to determine the levels of IgM, IgG and IgA rheumatoid factors (RF) in 16 patients suffering from full-blown AIDS and 32 patients with AIDS-related complex (ARC), in the clinical form of lymphoadenopathy syndrome (LAS), compared with 40 healthy, young heterosexual subjects. Both AIDS and ARC patients showed a greater incidence of high IgM RF levels, with mean values significantly higher than controls, but with no differences between the two pathological groups. IgG RF behaviour was similar in the two patient populations and the healthy subjects. IgA RF were significantly raised in AIDS and ARC. Further information on RF was obtained by determination of the immunoglobulin levels of the respective isotypes in the same patients. Mean IgG levels were above normal in AIDS and ARC patients, but the latter group showed a higher incidence of increased values and higher mean levels. The IgA isotype was significantly increased mainly in AIDS patients. The behaviour of IgM was virtually the same in the three groups studied. A difference between AIDS and ARC patients was established by the detection of circulating immune-complexes (IC) by the C1q-binding and CIC-conglutinin assays. IC were significantly high, by both methods, only in the ARC group, but normal or very low in AIDS. These overall findings suggest once again the impairment of B cell function in AIDS, with prevalent hyperactivation in ARC and exhaustion in full-blown AIDS, and apparent preservation, in the latter group, of the antibody responses which are more closely related to the activity of subsets of T helper cells. PMID:3608224

  12. S100A8 and S100A9: DAMPs at the Crossroads between Innate Immunity, Traditional Risk Factors, and Cardiovascular Disease

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    Alexandru Schiopu

    2013-01-01

    Full Text Available Amplification of innate immune responses by endogenous danger-associated molecular patterns (DAMPs promotes inflammation. The involvement of S100A8 and S100A9, DAMPs belonging to the S100 calgranulin family, in the pathogenesis of cardiovascular disease is attracting an increasing amount of interest. S100A8 and S100A9 (also termed MRP8 and MRP14 preferentially form the S100A8/A9 heterodimer (MRP8/14 or calprotectin and are constitutively expressed in myeloid cells. The levels of circulating S100A8/A9 in humans strongly correlate to blood neutrophil counts and are increased by traditional cardiovascular risk factors such as smoking, obesity, hyperglycemia, and dyslipidemia. S100A8/A9 is an endogenous ligand of toll-like receptor 4 (TLR4 and of the receptor for advanced glycation end products (RAGE and has been shown to promote atherogenesis in mice. In humans, S100A8/A9 correlates with the extent of coronary and carotid atherosclerosis and with a vulnerable plaque phenotype. S100A8/A9 is locally released following myocardial infarction and amplifies the inflammatory responses associated with myocardial ischemia/reperfusion injury. Elevated plasma levels of S100A8/A9 are associated with increased risk of future coronary events in healthy individuals and in myocardial infarction survivors. Thus, S100A8/A9 might represent a useful biomarker and therapeutic target in cardiovascular disease. Importantly, S100A8/A9 blockers have been developed and are approved for clinical testing.

  13. Aeromonas salmonicida Infection Only Moderately Regulates Expression of Factors Contributing to Toll-Like Receptor Signaling but Massively Activates the Cellular and Humoral Branches of Innate Immunity in Rainbow Trout (Oncorhynchus mykiss

    Directory of Open Access Journals (Sweden)

    Andreas Brietzke

    2015-01-01

    Full Text Available Toll-like receptors (TLRs are known to detect a defined spectrum of microbial structures. However, the knowledge about the specificity of teleost Tlr factors for distinct pathogens is limited so far. We measured baseline expression profiles of 18 tlr genes and associated signaling factors in four immune-relevant tissues of rainbow trout Oncorhynchus mykiss. Intraperitoneal injection of a lethal dose of Aeromonas salmonicida subsp. salmonicida induced highly increased levels of cytokine mRNAs during a 72-hour postinfection (hpi period. In contrast, only the fish-specific tlr22a2 and the downstream factor irak1 featured clearly increased transcript levels, while the mRNA concentrations of many other tlr genes decreased. Flow cytometry quantified cell trafficking after infection indicating a dramatic influx of myeloid cells into the peritoneum and a belated low level immigration of lymphoid cells. T and B lymphocytes were differentiated with RT-qPCR revealing that B lymphocytes emigrated from and T lymphocytes immigrated into head kidney. In conclusion, no specific TLR can be singled out as a dominant receptor for A. salmonicida. The recruitment of cellular factors of innate immunity rather than induced expression of pathogen receptors is hence of key importance for mounting a first immune defense against invading A. salmonicida.

  14. Impact of the somatotrope Growth Hormone (GH)/Insulin-like Growth Factor 1 (IGF-1) axis upon thymus function: Pharmacological implications in regeneration of immune functions

    OpenAIRE

    Goffinet, Lindsay; Mottet, Marie; Kermani, Hamid; RENARD-CHARLET, Jeanne de Chantal; Geenen, Vincent; Martens, Henri

    2011-01-01

    The thymus is the central lymphoid structure where T-cell differentiation takes place, and a crucial organ for the maintenance of homeostasis in the immune system. Thymopoiesis includes intrathymic proliferation of T-cell precursors, selection and output of both self-tolerant and competent effector T cells, as well as of natural regulatory T cells (nTreg). In the crosstalk between the neuroendocrine and immune systems, peptide hormones have been more and more implicated in immunomodulation fo...

  15. Immunizations: Active vs. Passive

    Science.gov (United States)

    ... Prevention > Immunizations > Immunizations: Active vs. Passive Safety & Prevention Listen Español Text Size Email Print Share Immunizations: Active vs. Passive Page Content Article Body Pediatricians can ...

  16. Expression of RNA-interference/antisense transgenes by the cognate promoters of target genes is a better gene-silencing strategy to study gene functions in rice.

    Directory of Open Access Journals (Sweden)

    Jing Li

    Full Text Available Antisense and RNA interference (RNAi-mediated gene silencing systems are powerful reverse genetic methods for studying gene function. Most RNAi and antisense experiments used constitutive promoters to drive the expression of RNAi/antisense transgenes; however, several reports showed that constitutive promoters were not expressed in all cell types in cereal plants, suggesting that the constitutive promoter systems are not effective for silencing gene expression in certain tissues/organs. To develop an alternative method that complements the constitutive promoter systems, we constructed RNAi and/or antisense transgenes for four rice genes using a constitutive promoter or a cognate promoter of a selected rice target gene and generated many independent transgenic lines. Genetic, molecular, and phenotypic analyses of these RNAi/antisense transgenic rice plants, in comparison to previously-reported transgenic lines that silenced similar genes, revealed that expression of the cognate promoter-driven RNAi/antisense transgenes resulted in novel growth/developmental defects that were not observed in transgenic lines expressing constitutive promoter-driven gene-silencing transgenes of the same target genes. Our results strongly suggested that expression of RNAi/antisense transgenes by cognate promoters of target genes is a better gene-silencing approach to discovery gene function in rice.

  17. Crystal structure of 70S ribosome with both cognate tRNAs in the E and P sites representing an authentic elongation complex.

    Directory of Open Access Journals (Sweden)

    Shu Feng

    Full Text Available During the translation cycle, a cognate deacylated tRNA can only move together with the codon into the E site. We here present the first structure of a cognate tRNA bound to the ribosomal E site resulting from translocation by EF-G, in which an entire L1 stalk (L1 protein and L1 rRNA interacts with E-site tRNA (E-tRNA, representing an authentic ribosome elongation complex. Our results revealed that the Watson-Crick base pairing is formed at the first and second codon-anticodon positions in the E site in the ribosome elongation complex, whereas the codon-anticodon interaction in the third position is indirect. Analysis of the observed conformations of mRNA and E-tRNA suggests that the ribosome intrinsically has the potential to form codon-anticodon interaction in the E site, independently of the mRNA configuration. We also present a detailed description of the biologically relevant position of the entire L1 stalk and its interacting cognate E-tRNA, which provides a better understanding of the structural basis for translation elongation. Furthermore, to gain insight into translocation, we report the positioning of protein L6 contacting EF-G, as well as the conformational change of the C-terminal tail of protein S13 in the decoding center.

  18. Expression of RNA-interference/antisense transgenes by the cognate promoters of target genes is a better gene-silencing strategy to study gene functions in rice.

    Science.gov (United States)

    Li, Jing; Jiang, Dagang; Zhou, Hai; Li, Feng; Yang, Jiawei; Hong, Laifa; Fu, Xiao; Li, Zhibin; Liu, Zhenlan; Li, Jianming; Zhuang, Chuxiong

    2011-03-03

    Antisense and RNA interference (RNAi)-mediated gene silencing systems are powerful reverse genetic methods for studying gene function. Most RNAi and antisense experiments used constitutive promoters to drive the expression of RNAi/antisense transgenes; however, several reports showed that constitutive promoters were not expressed in all cell types in cereal plants, suggesting that the constitutive promoter systems are not effective for silencing gene expression in certain tissues/organs. To develop an alternative method that complements the constitutive promoter systems, we constructed RNAi and/or antisense transgenes for four rice genes using a constitutive promoter or a cognate promoter of a selected rice target gene and generated many independent transgenic lines. Genetic, molecular, and phenotypic analyses of these RNAi/antisense transgenic rice plants, in comparison to previously-reported transgenic lines that silenced similar genes, revealed that expression of the cognate promoter-driven RNAi/antisense transgenes resulted in novel growth/developmental defects that were not observed in transgenic lines expressing constitutive promoter-driven gene-silencing transgenes of the same target genes. Our results strongly suggested that expression of RNAi/antisense transgenes by cognate promoters of target genes is a better gene-silencing approach to discovery gene function in rice.

  19. Expression and function of cannabinoid receptors CB1 and CB2 and their cognate cannabinoid ligands in murine embryonic stem cells.

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    Shuxian Jiang

    Full Text Available BACKGROUND: Characterization of intrinsic and extrinsic factors regulating the self-renewal/division and differentiation of stem cells is crucial in determining embryonic stem (ES cell fate. ES cells differentiate into multiple hematopoietic lineages during embryoid body (EB formation in vitro, which provides an experimental platform to define the molecular mechanisms controlling germ layer fate determination and tissue formation. METHODS AND FINDINGS: The cannabinoid receptor type 1 (CB1 and cannabinoid receptor type 2 (CB2 are members of the G-protein coupled receptor (GPCR family, that are activated by endogenous ligands, the endocannabinoids. CB1 receptor expression is abundant in brain while CB2 receptors are mostly expressed in hematopoietic cells. However, the expression and the precise roles of CB1 and CB2 and their cognate ligands in ES cells are not known. We observed significant induction of CB1 and CB2 cannabinoid receptors during the hematopoietic differentiation of murine ES (mES-derived embryoid bodies. Furthermore, mES cells as well as ES-derived embryoid bodies at days 7 and 14, expressed endocannabinoids, the ligands for both CB1 and CB2. The CB1 and CB2 antagonists (AM251 and AM630, respectively induced mES cell death, strongly suggesting that endocannabinoids are involved in the survival of mES cells. Treatment of mES cells with the exogenous cannabinoid ligand Delta(9-THC resulted in the increased hematopoietic differentiation of mES cells, while addition of AM251 or AM630 blocked embryoid body formation derived from the mES cells. In addition, cannabinoid agonists induced the chemotaxis of ES-derived embryoid bodies, which was specifically inhibited by the CB1 and CB2 antagonists. CONCLUSIONS: This work has not been addressed previously and yields new information on the function of cannabinoid receptors, CB1 and CB2, as components of a novel pathway regulating murine ES cell differentiation. This study provides insights

  20. Granulocyte-macrophage stimulating factor (GM-CSF) increases circulating dendritic cells but does not abrogate suppression of adaptive cellular immunity in patients with metastatic colorectal cancer receiving chemotherapy.

    Science.gov (United States)

    Martinez, Micaela; Ono, Nadia; Planutiene, Marina; Planutis, Kestutis; Nelson, Edward L; Holcombe, Randall F

    2012-01-23

    Advanced cancer and chemotherapy are both associated with immune system suppression. We initiated a clinical trial in patients receiving chemotherapy for metastatic colorectal cancer to determine if administration of GM-CSF in this setting was immunostimulatory. Between June, 2003 and January, 2007, 20 patients were enrolled in a clinical trial (NCT00257322) in which they received 500 ug GM-CSF daily for 4 days starting 24 hours after each chemotherapy cycle. There were no toxicities or adverse events reported. Blood was obtained before chemotherapy/GM-CSF administration and 24 hours following the final dose of GM-CSF and evaluated for circulating dendritic cells and adaptive immune cellular subsets by flow cytometry. Peripheral blood mononuclear cell (PBMC) expression of γ-interferon and T-bet transcription factor (Tbx21) by quantitative real-time PCR was performed as a measure of Th1 adaptive cellular immunity. Pre- and post-treatment (i.e., chemotherapy and GM-CSF) samples were evaluable for 16 patients, ranging from 1 to 5 cycles (median 3 cycles, 6 biologic sample time points). Dendritic cells were defined as lineage (-) and MHC class II high (+). 73% of patients had significant increases in circulating dendritic cells of ~3x for the overall group (5.8% to 13.6%, p = 0.02) and ~5x excluding non-responders (3.2% to 14.5%, p cellular immunity in patients with metastatic colorectal cancer but demonstrates that mid-cycle administration of GM-CSF can significantly increase the proportion of circulating dendritic cells. As the role of dendritic cells in anti-tumor immunity becomes better defined, GM-CSF administration may provide a non-toxic intervention to augment this arm of the immune system for cancer patients receiving cytotoxic therapy. ClinicalTrials.gov: NCT00257322.

  1. Adult Immunization

    Directory of Open Access Journals (Sweden)

    Omer Coskun

    2008-04-01

    Full Text Available Despite the many advances in modern medicine, each year thousands of people in the world die from diseases that are easily prevented by safe and effective vaccines. Few measures in preventive medicine are of such proven value and as easy to implement as routine immunization against infectious diseases. Prevention of infection by immunization is a lifelong process. There are a number of vaccines that all adults (¡I18 years require. There are also other vaccines that need to be tailored to meet individual variations in risk resulting from occupation, foreign travel, underlying illness, lifestyle and age. In this study, we tried to review this important subject. [TAF Prev Med Bull 2008; 7(2.000: 159-166

  2. Crystal Structure of the Escherichia coli Fic Toxin-Like Protein in Complex with Its Cognate Antitoxin

    Science.gov (United States)

    Stanger, Frédéric V.; Harms, Alexander; Dehio, Christoph; Schirmer, Tilman

    2016-01-01

    FIC domain proteins mediate post-translational modifications of target proteins, which typically results in their inactivation. Depending on the conservation of crucial active site residues, the FIC fold serves as structural scaffold for various enzymatic activities, mostly target adenylylation. The founding member of the vast Fic protein family, EcFicT, was identified in Escherichia coli some time ago. The G55R point mutant of EcFicT displays the “filamentation induced by cAMP” (Fic) phenotype at high 3',5'-cyclic adenosine monophosphate (cAMP) concentrations and elevated temperature, but the underlying molecular mechanism and any putative biochemical activity of EcFicT have remained unknown. EcFicT belongs to class I Fic toxin proteins that are encoded together with a small inhibitory protein (antitoxin), named EcFicA in E. coli. Here, we report the crystal structures of two mutant EcFicT/EcFicA complexes (EcFicTG55RA and EcFicTAE28G) both showing close resemblance with the structure of the AMP-transferase VbhT from Bartonella schoenbuchensis in complex with its cognate antitoxin VbhA. However, crucial differences in the active site of EcFicT compared to VbhT and other AMP-transferases rationalize the lack of evidence for adenylylation activity. Comprehensive bioinformatic analysis suggests that EcFicT has evolved from canonical AMP-transferases and has acquired a conserved binding site for a yet to be discovered novel substrate. The G55R mutation has no effect on structure or thermal stability of EcFicT, such that the molecular basis for its associated Fic phenotype remains elusive. We anticipate that this structure will inspire further bioinformatic and experimental analyses in order to characterize the enzymatic activity of EcFicT and help revealing its physiological role. PMID:27657533

  3. Structural basis for recognition of cognate tRNA by tyrosyl-tRNA synthetase from three kingdoms.

    Science.gov (United States)

    Tsunoda, Masaru; Kusakabe, Yoshio; Tanaka, Nobutada; Ohno, Satoshi; Nakamura, Masashi; Senda, Toshiya; Moriguchi, Tomohisa; Asai, Norio; Sekine, Mitsuo; Yokogawa, Takashi; Nishikawa, Kazuya; Nakamura, Kazuo T

    2007-01-01

    The specific aminoacylation of tRNA by tyrosyl-tRNA synthetases (TyrRSs) relies on the identity determinants in the cognate tRNA(Tyr)s. We have determined the crystal structure of Saccharomyces cerevisiae TyrRS (SceTyrRS) complexed with a Tyr-AMP analog and the native tRNA(Tyr)(GPsiA). Structural information for TyrRS-tRNA(Tyr) complexes is now full-line for three kingdoms. Because the archaeal/eukaryotic TyrRSs-tRNA(Tyr)s pairs do not cross-react with their bacterial counterparts, the recognition modes of the identity determinants by the archaeal/eukaryotic TyrRSs were expected to be similar to each other but different from that by the bacterial TyrRSs. Interestingly, however, the tRNA(Tyr) recognition modes of SceTyrRS have both similarities and differences compared with those in the archaeal TyrRS: the recognition of the C1-G72 base pair by SceTyrRS is similar to that by the archaeal TyrRS, whereas the recognition of the A73 by SceTyrRS is different from that by the archaeal TyrRS but similar to that by the bacterial TyrRS. Thus, the lack of cross-reactivity between archaeal/eukaryotic and bacterial TyrRS-tRNA(Tyr) pairs most probably lies in the different sequence of the last base pair of the acceptor stem (C1-G72 vs G1-C72) of tRNA(Tyr). On the other hand, the recognition mode of Tyr-AMP is conserved among the TyrRSs from the three kingdoms.

  4. Research on Factors Affecting Children Planned Immunity Implementation and Countermeasures%影响儿童计划免疫实施因素分析及对策探讨

    Institute of Scientific and Technical Information of China (English)

    王翔云

    2015-01-01

    ObjectiveTo analyze factors affecting children planned immunity implementation and discuss the corresponding countermeasures.MethodsA total of 496 children vaccinated from October 2013 to February 2015 in our hospital as investigation objects. We used the form of questionnaire to survey 496 cases of children's parents,and colected children planned immunity vaccination and analyze the factors.Results The factors that influenced children planned immunity implementation were children living type,parents culture degree,average monthly income of family,whether to establish vaccination card and know the role of vaccine.ConclusionTo take corresponding measures according to the influencing factors,so as to improve the immunization coverage rate.%目的:分析影响儿童计划免疫实施的因素,并探讨相应对策。方法选择2013年10月~2015年2月在我院接种的496例儿童作为调查对象,采取调查问卷的形式对496例儿童家长进行问卷调查,收集,分析儿童计划免疫接种情况及有关影响因素。结果儿童的居住类型、父母的文化程度、家庭平均月收入、是否建立疫苗接种卡及是否知道疫苗的作用,是影响儿童计划免疫实施的因素。结论根据影响因素采取相应的措施,从而提高计划免疫的接种率。

  5. 炎症-免疫因素与子痫前期发病机制研究进展%Inflammation and immune factors involve in the pathogenesis of preeclampsia

    Institute of Scientific and Technical Information of China (English)

    孔艳; 李小芳; 孔祥

    2016-01-01

    Preeclampsia is a common disease in department of obstetrics, which has serious influence on mother and fetus. Some studies have shown that many factors involved in the pathogenesis of preeclampsia. The changes of inflammation and the immune system are important factors of preeclampsia. Patients with preeclampsia have serious inflammation, and immune damage occured on maternal-fetal interface, which enhanced the immune balance. The article mainly focused on NF-κB, CXCL10 and the relation with other factors to expound the pathogenesis of preeclampsia.%子痫前期是产科常见疾病,严重影响母儿结局。研究表明多种因素参与子痫前期的发病,炎症免疫因素是子痫前期发病的一个重要因素。子痫前期患者体内存在严重的炎症反应,免疫破坏作用增强导致母胎界面免疫平衡被打破。文中主要从核因子-κB(NF-κB)、CXC 类趋化因子10(CXCL10)两个因子入手阐述子痫前期发病的炎症免疫因素及与其他相关发病因素的联系。

  6. Immune Mechanisms in Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Andreas Glenthøj

    2016-06-01

    Full Text Available Myelodysplastic syndrome (MDS is a spectrum of diseases, characterized by debilitating cytopenias and a propensity of developing acute myeloid leukemia. Comprehensive sequencing efforts have revealed a range of mutations characteristic, but not specific, of MDS. Epidemiologically, autoimmune diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients—especially younger low-risk patients with HLA-DR15 tissue type—demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS.

  7. Immune Mechanisms in Myelodysplastic Syndrome

    DEFF Research Database (Denmark)

    Glenthøj, Andreas; Ørskov, Andreas Due; Hansen, Jakob Werner

    2016-01-01

    diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients......-especially younger low-risk patients with HLA-DR15 tissue type-demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune...... mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS....

  8. The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression.

    Science.gov (United States)

    Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Giao Ly, Nancy Ngoc; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Barilla, Rocky; Daley, Donnele; Greco, Stephanie H; Torres-Hernandez, Alejandro; Pergamo, Matthew; Ochi, Atsuo; Zambirinis, Constantinos P; Pansari, Mridul; Rendon, Mauricio; Tippens, Daniel; Hundeyin, Mautin; Mani, Vishnu R; Hajdu, Cristina; Engle, Dannielle; Miller, George

    2016-04-14

    Neoplastic pancreatic epithelial cells are believed to die through caspase 8-dependent apoptotic cell death, and chemotherapy is thought to promote tumour apoptosis. Conversely, cancer cells often disrupt apoptosis to survive. Another type of programmed cell death is necroptosis (programmed necrosis), but its role in pancreatic ductal adenocarcinoma (PDA) is unclear. There are many potential inducers of necroptosis in PDA, including ligation of tumour necrosis factor receptor 1 (TNFR1), CD95, TNF-related apoptosis-inducing ligand (TRAIL) receptors, Toll-like receptors, reactive oxygen species, and chemotherapeutic drugs. Here we report that the principal components of the necrosome, receptor-interacting protein (RIP)1 and RIP3, are highly expressed in PDA and are further upregulated by the chemotherapy drug gemcitabine. Blockade of the necrosome in vitro promoted cancer cell proliferation and induced an aggressive oncogenic phenotype. By contrast, in vivo deletion of RIP3 or inhibition of RIP1 protected against oncogenic progression in mice and was associated with the development of a highly immunogenic myeloid and T cell infiltrate. The immune-suppressive tumour microenvironment associated with intact RIP1/RIP3 signalling depended in part on necroptosis-induced expression of the chemokine attractant CXCL1, and CXCL1 blockade protected against PDA. Moreover, cytoplasmic SAP130 (a subunit of the histone deacetylase complex) was expressed in PDA in a RIP1/RIP3-dependent manner, and Mincle--its cognate receptor--was upregulated in tumour-infiltrating myeloid cells. Ligation of Mincle by SAP130 promoted oncogenesis, whereas deletion of Mincle protected against oncogenesis and phenocopied the immunogenic reprogramming of the tumour microenvironment that was induced by RIP3 deletion. Cellular depletion suggested that whereas inhibitory macrophages promote tumorigenesis in PDA, they lose their immune-suppressive effects when RIP3 or Mincle is deleted. Accordingly, T cells

  9. 流动儿童免疫规划疫苗接种率影响因素分析%Analyses of factors influencing the coverage of national immunization program vaccines in migrant children in Wenzhou

    Institute of Scientific and Technical Information of China (English)

    林献丹; 陈玲萍; 郑晓春; 李万仓; 王志刚; 邓泽静

    2011-01-01

    [Objective]The investigation was carried out to better understand the factors influencing the coverage of national immunization program (NIP) vaccines in migrant children in Wenzhou, and to improve the immunization coverage of these vaccines.[Method]Population characteristics of 1 198 migrant children and their guardians, immunization situation of NIP vaccines, knowledge of the guardians on and their attitude towards preventive immunization, effectiveness of preventive immunization, were investigated in 15 towns from 3 counties in Wenzhou by using randomized sampling method.[Results]In the migrant children over one year old, who stayed in Wenzhou equal or more than 3 months, the coverage rates of BCG, OPV, DTP, MV, and H epB, were 86.8 %, 84.9 %, 81.5 %, 82.1%, and 80.35 %, respectively.Notably,the coverage rate of these five vaccines was only 66.4 %.Multi-factors analysis revealed that the iow coverage rate of five vaccines was mainly influenced by the staying time and birth place of migrant children, their family economy, having immunization card, cost of preventive immunization, their guardians' attitude towards to preventive immunization.[Conclusion]Vaccination rate was low in migrant children, many factors were influence it, and it should be taken targeted intervention to imporve immune status.%[目的]探讨影响温州市流动儿童国家免疫规划(national immunization program,NIP)疫苗预防接种的因素,为制订有效的干预措施提供依据. [方法]采用分阶段整群随机抽样方法,调查温州市3个县(市、区)的15个乡(镇、街道)1 543名流动儿童和监护人的人口学特征,NIP疫苗预防接种,监护人预防接种知识、态度、预防接种服务及利用情况,分析影响流动儿童NIP疫苗接种率的因素. [结果] 1 198名居住时间≥3个月的1岁以上流动儿童卡介苗(BCG)、口服脊髓灰质炎减毒活疫苗(OPV)、百日咳-白喉-破伤风联合疫苗(DTP)、麻疹减毒活疫苗(MV

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

    Science.gov (United States)

    Nakada-Tsukui, Kumiko; Nozaki, Tomoyoshi

    2016-01-01

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

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

    Science.gov (United States)

    Nakada-Tsukui, Kumiko; Nozaki, Tomoyoshi

    2016-01-01

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

  12. The Effect of Lupinus albus and Calcium Chloride on Growth Performance, Body Composition, Plasma Biochemistry and Meat Quality of Male Pigs Immunized Against Gonadotrophin Releasing Factor

    Directory of Open Access Journals (Sweden)

    Karen Moore

    2016-12-01

    Full Text Available Two hundred and ninety-four pigs were used to assess the effect of two ingredients (Lupinus albus (albus lupins or a combination of calcium chloride and sodium tri-polyphosphate (mineral salts on growth performance, body composition and objective meat quality of pigs immunized against gonadotrophin releasing factor (immunocastrates and entire male pigs in the late finishing phase. Pigs fed mineral salts ate less feed than those fed the control diet with no effect on growth rate (p > 0.05, backfat (p > 0.05 or fat deposition (p > 0.05. Pigs fed albus lupins had a reduced feed intake (p < 0.001 for all time periods, lower growth rate (p < 0.001 for all time periods, lower backfat (p < 0.005 and decreased fat deposition (p < 0.001 for all time periods compared to those fed the control diet or mineral salts. From day (d 0–28 pigs fed mineral salts had a better feed conversion ratio (p = 0.001 than those fed albus lupins who in turn had an improved feed conversion compared to the control diet. Immunocastrates had thicker backfat than entire males at the end of the experiment (p < 0.001, however, feeding albus lupins to immunocastrated males reduced backfat thickness to similar to entire males fed the control diet (p = 0.01. With the exception of the increased muscle pH at 45 minutes post-exsanguination in mineral salts and albus lupins compared with the control diet (p = 0.03 there was no effect of diet on objective pork quality. Pork from IC males had a higher ultimate pH (p < 0.001, was lighter (L*; p = 0.003, more yellow (p = 0.008 and had a higher drip loss (p < 0.001 compared to entire males. Albus lupins show potential in reducing the increase in feed intake and backfat associated with immunocastration. Mineral salts may be useful in situations where a reduction in feed intake and an improvement in feed conversion is desired and reducing fat deposition is not the objective.

  13. Lack of macrophage migration inhibitory factor in mice does not affect hallmarks of the inflammatory/immune response during the first week after stroke

    Directory of Open Access Journals (Sweden)

    Deierborg Tomas

    2011-06-01

    Full Text Available Abstract Background Macrophage migration inhibitory factor (MIF has been proposed to play a detrimental role in stroke. We recently showed that MIF promotes neuronal death and aggravates neurological deficits during the first week after experimental stroke, in mice. Since MIF regulates tissue inflammation, we studied the putative role of MIF in post-stroke inflammation. Methods We subjected C57BL/6 mice, Mif-/- (MIF-KO or Mif+/+ (WT, to a transient occlusion of the right middle cerebral artery (tMCAo or sham-surgery. We studied MIF expression, GFAP expression and the number of CD74-positive cells in the ischemic brain hemisphere 7 days after tMCAo using primarily immunohistochemistry. We determined IFN-γ, IL-2, IL-4, IL-5, IL-10, IL-12, KC/CXCL-1 and TNF-α protein levels in the brain (48 h after surgery and serum (48 h and 7 days after surgery by a multiplex immunoassay. Results We observed that MIF accumulates in neurons and astrocytes of the peri-infarct region, as well as in microglia/macrophages of the infarct core up to 7 days after stroke. Among the inflammatory mediators analyzed, we found a significant increase in cerebral IL-12 and KC levels after tMCAo, in comparison to sham-surgery. Importantly, the deletion of Mif did not significantly affect the levels of the cytokines evaluated, in the brain or serum. Moreover, the spleen weight 48 h and 7 days subsequent to tMCAo was similar in WT and MIF-KO mice. Finally, the extent of GFAP immunoreactivity and the number of MIF receptor (CD74-positive cells within the ischemic brain hemisphere did not differ significantly between WT and MIF-KO mice subjected to tMCAo. Conclusions We conclude that MIF does not affect major components of the inflammatory/immune response during the first week after experimental stroke. Based on present and previous evidence, we propose that the deleterious MIF-mediated effects in stroke depend primarily on an intraneuronal and/or interneuronal action.

  14. Lymphoma: Immune Evasion Strategies

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-04-30

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

  15. Maternal immune activation by poly(I:C induces expression of cytokines IL-1β and IL-13, chemokine MCP-1 and colony stimulating factor VEGF in fetal mouse brain

    Directory of Open Access Journals (Sweden)

    Arrode-Brusés Géraldine

    2012-04-01

    Full Text Available Abstract Background Maternal viral infection during pregnancy is associated with an increase in the incidence of psychiatric disorders with presumed neurodevelopmental origin, including autism spectrum disorders and schizophrenia. The enhanced risk for developing mental illness appears to be caused by deleterious effects of innate immune response-associated factors on the development of the central nervous system, which predispose the offspring to pathological behaviors in adolescence and adulthood. To identify the immune response-associated soluble factors that may affect central nervous system development, we examined the effect of innate immune response activation by polyriboinosinic-polyribocytidylic acid (poly(I:C, a synthetic analogue of viral double-stranded RNA, on the expression levels of pro- and anti-inflammatory cytokines, chemokines and colony stimulating factors in fetal and postnatal mouse brain 6 h and 24 h after treatment. Methods C57BL/6J pregnant mice (gestational day 16 or newborn mice (postnatal day 4 received a single intraperitoneal injection of the synthetic analogue of viral double-stranded RNA poly(I:C (20 mg/kg. Thirty-two immune response-associated soluble factors, including pro- and anti-inflammatory cytokines, chemokines and colony stimulating factors, were assayed 6 h and 24 h after poly(I:C injection using multiplexed bead-based immunoassay (Milliplex Map and processed in a Luminex 100 IS instrument. Results Maternal exposure to poly(I:C at gestational day 16 induced a significant increase in cytokines interleukin (IL-1β, IL-7 and IL-13; chemokines monocyte chemoattractant protein 1 (MCP-1, macrophage inflammatory protein (MIP-1α, interferon gamma-induced protein (IP-10 and monokine induced by IFN-gamma (MIG; and in the colony stimulating factor vascular endothelial growth factor (VEGF in the fetal brain. IL-1β showed the highest concentration levels in fetal brains and was the only cytokine

  16. Alternative adaptive immunity in invertebrates

    DEFF Research Database (Denmark)

    Kurtz, Joachim; Armitage, Sophie Alice Octavia

    2006-01-01

    Vertebrate adaptive immunity is characterized by challenge-specific long-term protection. This specific memory is achieved through the vast diversity of somatically rearranged immunological receptors such as antibodies. Whether or not invertebrates are capable of a comparable phenotypic plasticity...... and memory has long been a matter of debate. A recent study on Anopheles gambiae mosquitoes now establishes Down syndrome cell adhesion molecule (Dscam) as a key immune surveillance factor with characteristics analogous to antibodies....

  17. Human monoclonal antibodies against anthrax lethal factor and protective antigen act independently to protect against Bacillus anthracis infection and enhance endogenous immunity to anthrax

    NARCIS (Netherlands)

    Albrecht, Mark T.; Li, Han; Williamson, E. Diane; LeButt, Chris S.; Flick-Smith, Helen C.; Quinn, Conrad P.; Westra, Hans; Galloway, Darrell; Mateczun, Alfred; Goldman, Stanley; Groen, Herman; Baillie, Les W. J.

    2007-01-01

    The unpredictable nature of bioterrorism and the absence of real-time detection systems have highlighted the need for an efficient postexposure therapy for Bacillus anthracis infection. One approach is passive immunization through the administration of antibodies that mitigate the biological action

  18. Human monoclonal antibodies against anthrax lethal factor and protective antigen act independently to protect against Bacillus anthracis infection and enhance endogenous immunity to anthrax

    NARCIS (Netherlands)

    Albrecht, Mark T.; Li, Han; Williamson, E. Diane; LeButt, Chris S.; Flick-Smith, Helen C.; Quinn, Conrad P.; Westra, Hans; Galloway, Darrell; Mateczun, Alfred; Goldman, Stanley; Groen, Herman; Baillie, Les W. J.

    2007-01-01

    The unpredictable nature of bioterrorism and the absence of real-time detection systems have highlighted the need for an efficient postexposure therapy for Bacillus anthracis infection. One approach is passive immunization through the administration of antibodies that mitigate the biological action

  19. The nuclear factor-κB inhibitor pyrrolidine dithiocarbamate reduces polyinosinic-polycytidilic acid-induced immune response in pregnant rats and the behavioral defects of their adult offspring

    Directory of Open Access Journals (Sweden)

    Song Xueqin

    2011-12-01

    Full Text Available Abstract Background Epidemiological studies have indicated that maternal infection during pregnancy may lead to a higher incidence of schizophrenia in the offspring. It is assumed that the maternal infection increases the immune response, leading to neurodevelopmental disorders in the offspring. Maternal polyinosinic-polycytidilic acid (PolyI:C treatment induces a wide range of characteristics in the offspring mimicking some schizophrenia symptoms in humans. These observations are consistent with the neurodevelopmental hypothesis of schizophrenia. Methods We examined whether suppression of the maternal immune response could prevent neurodevelopmental disorders in adult offspring. PolyI:C or saline was administered to early pregnant rats to mimic maternal infection, and the maternal immune response represented by tumor necrosis factor alpha (TNF-α and interleukin-10 (IL-10 levels was determined by enzyme-linked immunosorbent assays (ELISA. The NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC was used to suppress the maternal immune response. Neurodevelopmental disorders in adult offspring were examined by prepulse inhibition (PPI, passive avoidance, and active avoidance tests. Results PolyI:C administration to early pregnant rats led to elevated serum cytokine levels as shown by massive increases in serum TNF-α and IL-10 levels. The adult offspring showed defects in prepulse inhibition, and passive avoidance and active avoidance tests. PDTC intervention in early pregnant rats suppressed cytokine increases and reduced the severity of neurodevelopmental defects in adult offspring. Conclusions Our findings suggest that PDTC can suppress the maternal immune response induced by PolyI:C and partially prevent neurodevelopmental disorders of adult offspring.

  20. Anti-HBV efficacy of combined siRNAs targeting viral gene and heat shock cognate 70

    Directory of Open Access Journals (Sweden)

    Bian Zhongqi

    2012-11-01

    Full Text Available Abstract Background Hepatitis B virus (HBV infection is a major health concern with more than two billion individuals currently infected worldwide. Because of the limited effectiveness of existing vaccines and drugs, development of novel antiviral strategies is urgently needed. Heat stress cognate 70 (Hsc70 is an ATP-binding protein of the heat stress protein 70 family. Hsc70 has been found to be required for HBV DNA replication. Here we report, for the first time, that combined siRNAs targeting viral gene and siHsc70 are highly effective in suppressing ongoing HBV expression and replication. Methods We constructed two plasmids (S1 and S2 expressing short hairpin RNAs (shRNAs targeting surface open reading frame of HBV(HBVS and one plasmid expressing shRNA targeting Hsc70 (siHsc70, and we used the EGFP-specific siRNA plasmid (siEGFP as we had previously described. First, we evaluated the gene-silencing efficacy of both shRNAs using an enhanced green fluorescent protein (EGFP reporter system and flow cytometry in HEK293 and T98G cells. Then, the antiviral potencies of HBV-specific siRNA (siHBV in combination with siHsc70 in HepG2.2.15 cells were investigated. Moreover, type I IFN and TNF-α induction were measured by quantitative real-time PCR and ELISA. Results Cotransfection of either S1 or S2 with an EGFP plasmid produced an 80%–90% reduction in EGFP signal relative to the control. This combinational RNAi effectively and specifically inhibited HBV protein, mRNA and HBV DNA, resulting in up to a 3.36 log10 reduction in HBV load in the HepG2.2.15 cell culture supernatants. The combined siRNAs were more potent than siHBV or siHsc70 used separately, and this approach can enhance potency in suppressing ongoing viral gene expression and replication in HepG2.2.15 cells while forestalling escape by mutant HBV. The antiviral synergy of siHBV used in combination with siHsc70 produced no cytotoxicity and induced no production of IFN-α, IFN-β and TNF

  1. The stress protein heat shock cognate 70 (Hsc70) inhibits the Transient Receptor Potential Vanilloid type 1 (TRPV1) channel

    Science.gov (United States)

    Iftinca, Mircea; Flynn, Robyn; Basso, Lilian; Melo, Helvira; Aboushousha, Reem; Taylor, Lauren

    2016-01-01

    Background Specialized cellular defense mechanisms prevent damage from chemical, biological, and physical hazards. The heat shock proteins have been recognized as key chaperones that maintain cell survival against a variety of exogenous and endogenous stress signals including noxious temperature. However, the role of heat shock proteins in nociception remains poorly understood. We carried out an expression analysis of the constitutively expressed 70 kDa heat-shock cognate protein, a member of the stress-induced HSP70 family in lumbar dorsal root ganglia from a mouse model of Complete Freund’s Adjuvant-induced chronic inflammatory pain. We used immunolabeling of dorsal root ganglion neurons, behavioral analysis and patch clamp electrophysiology in both dorsal root ganglion neurons and HEK cells transfected with Hsc70 and Transient Receptor Potential Channels to examine their functional interaction in heat shock stress condition. Results We report an increase in protein levels of Hsc70 in mouse dorsal root ganglia, 3 days post Complete Freund’s Adjuvant injection in the hind paw. Immunostaining of Hsc70 was observed in most of the dorsal root ganglion neurons, including the small size nociceptors immunoreactive to the TRPV1 channel. Standard whole-cell patch-clamp technique was used to record Transient Receptor Potential Vanilloid type 1 current after exposure to heat shock. We found that capsaicin-evoked currents are inhibited by heat shock in dorsal root ganglion neurons and transfected HEK cells expressing Hsc70 and TRPV1. Blocking Hsc70 with matrine or spergualin compounds prevented heat shock-induced inhibition of the channel. We also found that, in contrast to TRPV1, both the cold sensor channels TRPA1 and TRPM8 were unresponsive to heat shock stress. Finally, we show that inhibition of TRPV1 depends on the ATPase activity of Hsc70 and involves the rho-associated protein kinase. Conclusions Our work identified Hsc70 and its ATPase activity as a central

  2. Prevalence and associated factors of partially/non-immunization of under-five in Goma city, Democratic Republic of Congo: a community-based cross-sectional survey

    Science.gov (United States)

    Kabudi, André Mwanishayi; Lutala, Prosper Mukobelwa; Kazadi, Junior Mulaja; Bardella, Inis Jane

    2015-01-01

    Introduction At the East part of DRC, anecdotal reports are advancing several causes of unsuccessful campaigns of vaccination by the time going: rumors about use of vaccines for killing purpose, injection of vaccine to decrease the reproductive potential in coming generations, use of vaccines by some rebellions and neighboring countries to kill children indirectly, ineffectiveness of vaccines currently on the market. While those rumors seem to be less reliable, potential beneficiaries are taking them seriously and justifying a reluctance to bring their children or siblings for immunization. Against this above background, our community Primary Health Care team indicates that still, in Goma city in general and even in the referral hospital catchment area, there are children who have never been vaccinated. Objectives To determine the prevalence and determinants of non-immunization of under-five children in Goma City. Study design Cross-sectional community-based survey. Methods A sample size of 384 children aged under-five years from the target population was used for the study. The ratio of under-five years of age Goma city to the total population of Goma city for the year 2012 was considered as the study population frame. Results The prevalence of under-five non-immunized children was 25.7%. There was an association between immunization status of children and their gender, school characteristics, age, sibling, the level of literacy, the marital status of their parents and the age of their mothers. Conclusion For improving the quality of under-five children immunization, the medical authorities must consider these different determinants. PMID:26029327

  3. Differential effect of immune cells on non-pathogenic Gram-negative bacteria-induced nuclear factor-kappaB activation and pro-inflammatory gene expression in intestinal epithelial cells

    DEFF Research Database (Denmark)

    Haller, D.; Holt, L.; Parlesak, Alexandr;

    2004-01-01

    of immune-epithelial cell cross-talk on Gram-negative enteric bacteria-induced NF-kappaB signalling and pro-inflammatory gene expression in IEC using HT-29/MTX as well as CaCO-2 transwell cultures Interestingly, while differentiated HT-29/MTX cells are unresponsive to non-pathogenic Gram negative bacterial......-kappaB signalling and IL-8 gene expression in IEC cocultured with immune cells and suggests the presence of mechanisms that assure hyporesponsiveness of the intestinal epithelium to certain commensally enteric bacteria.......We have previously shown that non-pathogenic Gram negative bacteria induce RelA phosphorylation, nuclear factor (NF)-kappaB transcriptional activity and pro-inflammatory gene expression in intestinal epithelial cells (IEC) in vivo and in vitro. In this study, we investigated the molecular mechanism...

  4. Immune Vasculitis Induced Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The relationship between immune vasculitis and atherosclerosis was studied. The experimental model of weanling rabbits for immune vasculitis was reproduced by intravenous injection of 10 % bovine serum albumin. There were 6 groups: group A, 25 weanling rabbits with immune vasculitis subject to coronary arteriography; group B, 10 normal mature rabbits subject to coronary arteriography; group C, 10 weanling rabbits subject to coronary arteriography; group D, 8 weanling rabbits with vasculitis and cholesterol diet; group E, 8 weanling rabbits receiving single cholesterol diet; group F: 8 weanling rabbits receiving basic diet. Four weeks later, coronary arteriography was performed in groups A, B and C. The rabbits in groups D, E and F were sacrificed for the study of pathological changes in the coronary artery after 12 weeks. The results showed that the dilatation of coronary artery occurred in 6 rabbits of group A, but in groups B and C, no dilatation of coronary artery appeared. In comparison with group E, more severe atherosclerosis occurred in group D, showing the thickened plaque, fibrous sclerosis and atherosclerotic lesion. Percentage of plaques covering aortic intima, incidence of atherosclerosis of small coronary arteries and degree of stenosis of coronary arteries were significantly higher in group D than in group E (P<0.01). No atherosclerosis changes were found in group F. It was concluded that in the acute phase, the serum immune vasculitis can induce the dilatation of coronary artery of some weanling rabbits, and aggravate the formation of atherosclerosis in rabbits fed with cholesterol diet. Immune vasculitis is a new risk factor of atherosclerosis and ischemic heart disease.

  5. Fine-Tuning of the RIG-I-Like Receptor/Interferon Regulatory Factor 3-Dependent Antiviral Innate Immune Response by the Glycogen Synthase Kinase 3/β-Catenin Pathway.

    Science.gov (United States)

    Khan, Kashif Aziz; Dô, Florence; Marineau, Alexandre; Doyon, Priscilla; Clément, Jean-François; Woodgett, James R; Doble, Bradley W; Servant, Marc J

    2015-09-01

    Induction of an antiviral innate immune response relies on pattern recognition receptors, including retinoic acid-inducible gene 1-like receptors (RLR), to detect invading pathogens, resulting in the activation of multiple latent transcription factors, including interferon regulatory factor 3 (IRF3). Upon sensing of viral RNA and DNA, IRF3 is phosphorylated and recruits coactivators to induce type I interferons (IFNs) and selected sets of IRF3-regulated IFN-stimulated genes (ISGs) such as those for ISG54 (Ifit2), ISG56 (Ifit1), and viperin (Rsad2). Here, we used wild-type, glycogen synthase kinase 3α knockout (GSK-3α(-/-)), GSK-3β(-/-), and GSK-3α/β double-knockout (DKO) embryonic stem (ES) cells, as well as GSK-3β(-/-) mouse embryonic fibroblast cells in which GSK-3α was knocked down to demonstrate that both isoforms of GSK-3, GSK-3α and GSK-3β, are required for this antiviral immune response. Moreover, the use of two selective small-molecule GSK-3 inhibitors (CHIR99021 and BIO-acetoxime) or ES cells reconstituted with the catalytically inactive versions of GSK-3 isoforms showed that GSK-3 activity is required for optimal induction of antiviral innate immunity. Mechanistically, GSK-3 isoform activation following Sendai virus infection results in phosphorylation of β-catenin at S33/S37/T41, promoting IRF3 DNA binding and activation of IRF3-regulated ISGs. This study identifies the role of a GSK-3/β-catenin axis in antiviral innate immunity.

  6. Innate Immunity and Breast Milk

    Science.gov (United States)

    Cacho, Nicole Theresa; Lawrence, Robert M.

    2017-01-01

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

  7. Immune system modifications and feto-maternal immune tolerance.

    Science.gov (United States)

    Song, Dan; Shi, Yichao

    2014-01-01

    This review aimed at understanding pregnancy-induced changes in the maternal immune response and mechanisms for the establishment of feto-maternal tolerance. Articles cited in this review were obtained from PubMed in English from 2000 to 2014, and the search string included keywords such as feto-maternal tolerance, dendritic cells, macrophage, T regulatory cells, natural killer cells, cytokines and hormone. Articles regarding altered maternal immune response, including the proliferation and differentiation of the altered cells, and the production of cytokines and regulation of hormones in the feto-maternal interface were retrieved, reviewed and analyzed. The changes in immune cells and cytokines in the local uterine microenvironment and peripheral blood are correlated with the establishment of feto-maternal tolerance. The endocrine system regulates the maternal immune system, promoting modifications during pregnancy. In these regulatory networks, every factor is indispensible for others. The integration and balance of these immune factors during pregnancy give rise to an environment that enables the fetus to escape rejection by the maternal immune system. This progress is complicated, and needs more comprehensive exploration and explanation.

  8. Immune system modifications and feto-maternal immune tolerance

    Institute of Scientific and Technical Information of China (English)

    Song Dan; Shi Yichao

    2014-01-01

    Objective This review aimed at understanding pregnancy-induced changes in the maternal immune response and mechanisms for the establishment of feto-maternal tolerance.Data sources Articles cited in this review were obtained from PubMed in English from 2000 to 2014,and the search string included keywords such as feto-maternal tolerance,dendritic cells,macrophage,T regulatory cells,natural killer cells,cytokines and hormone.Study selection Articles regarding altered maternal immune response,including the proliferation and differentiation of the altered cells,and the production of cytokines and regulation of hormones in the feto-maternal interface were retrieved,reviewed and analyzed.Results The changes in immune cells and cytokines in the local uterine microenvironment and peripheral blood are correlated with the establishment of feto-maternal tolerance.The endocrine system regulates the maternal immune system,promoting modifications during pregnancy.In these regulatory networks,every factor is indispensible for others.Conclusions The integration and balance of these immune factors during pregnancy give rise to an environment that enables the fetus to escape rejection by the maternal immune system.This progress is complicated,and needs more comprehensive exploration and explanation.

  9. Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity.

    Science.gov (United States)

    Hugues, Stéphanie; Fetler, Luc; Bonifaz, Laura; Helft, Julie; Amblard, François; Amigorena, Sebastian

    2004-12-01

    Induction of immunity and peripheral tolerance requires contacts between antigen-bearing dendritic cells (DCs) and cognate T cells. Using real-time two-photon microscopy, we have analyzed the dynamics of CD8(+) T cells in lymph nodes during the induction of antigen-specific immunity or tolerance. At 15-20 h after the induction of immunity, T cells stopped moving and established prolonged interactions with DCs. In tolerogenic conditions, despite effective initial T cell activation and proliferation, naive T cells remained motile and established serial brief contacts with multiple DCs. Thus, stable DC-T cell interactions occur during the induction of priming, whereas brief contacts may contribute to the induction of T cell tolerance.

  10. Multipronged attenuation of macrophage-colony stimulating factor signaling by Epstein-Barr virus BARF1

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Ann Hye-Ryong; Chang, Rhoda Ahn; Chen, Xiaoyan; Longnecker, Richard; He, Xiaolin [NWU

    2014-10-02

    The ubiquitous EBV causes infectious mononucleosis and is associated with several types of cancers. The EBV genome encodes an early gene product, BARF1, which contributes to pathogenesis, potentially through growth-altering and immune-modulating activities, but the mechanisms for such activities are poorly understood. We have determined the crystal structure of BARF1 in complex with human macrophage-colony stimulating factor (M-CSF), a hematopoietic cytokine with pleiotropic functions in development and immune response. BARF1 and M-CSF form a high-affinity, stable, ring-like complex in both solution and the crystal, with a BARF1 hexameric ring surrounded by three M-CSF dimers in triangular array. The binding of BARF1 to M-CSF dramatically reduces but does not completely abolish M-CSF binding and signaling through its cognate receptor FMS. A three-pronged down-regulation mechanism is proposed to explain the biological effect of BARF1 on M-CSF:FMS signaling. These prongs entail control of the circulating and effective local M-CSF concentration, perturbation of the receptor-binding surface of M-CSF, and imposition of an unfavorable global orientation of the M-CSF dimer. Each prong may reduce M-CSF:FMS signaling to a limited extent but in combination may alter M-CSF:FMS signaling dramatically. The downregulating mechanism of BARF1 underlines a viral modulation strategy, and provides a basis for understanding EBV pathogenesis.

  11. Covalent aspartylation of aspartyl-tRNA synthetase from Bakers' yeast by its cognat aspartyl adenylate: identification of the labeled residues

    Energy Technology Data Exchange (ETDEWEB)

    Mejdoub, H.; Kern, D.; Giege, R.; Ebel, J.P.; Boulanger, Y.; Reinbolt, J.

    1987-04-07

    Aspartyl-tRNA synthetase from bakers' yeast gives an unstable complex with the cognate adenylate, which reacts after dissociation with amino acid side chains of the protein. This leads to a covalent incorporation of (/sup 14/C)-aspartic acid into aspartyl-tRNA synthetase via amide or ester bonds formed between the ..cap alpha..-carboxyl group of activated aspartic acid and accessible lysines, serines, and threonines. This property is used to label the peptides at the surface of the enzyme. The main labeled residues have been identified, and their location in the primary structure is discussed in relation to structural properties of aspartyl-tRNA synthetase.

  12. VapC toxins from Mycobacterium tuberculosis are ribonucleases that differentially inhibit growth and are neutralized by cognate VapB antitoxins.

    Directory of Open Access Journals (Sweden)

    Bintou Ahmadou Ahidjo

    Full Text Available The chromosome of Mycobacterium tuberculosis (Mtb encodes forty seven toxin-antitoxin modules belonging to the VapBC family. The role of these modules in the physiology of Mtb and the function(s served by their expansion are unknown. We investigated ten vapBC modules from Mtb and the single vapBC from M. smegmatis. Of the Mtb vapCs assessed, only Rv0549c, Rv0595c, Rv2549c and Rv2829c were toxic when expressed from a tetracycline-regulated promoter in M. smegmatis. The same genes displayed toxicity when conditionally expressed in Mtb. Toxicity of Rv2549c in M. smegmatis correlated with the level of protein expressed, suggesting that the VapC level must exceed a threshold for toxicity to be observed. In addition, the level of Rv2456 protein induced in M. smegmatis was markedly lower than Rv2549c, which may account for the lack of toxicity of this and other VapCs scored as 'non-toxic'. The growth inhibitory effects of toxic VapCs were neutralized by expression of the cognate VapB as part of a vapBC operon or from a different chromosomal locus, while that of non-cognate antitoxins did not. These results demonstrated a specificity of interaction between VapCs and their cognate VapBs, a finding corroborated by yeast two-hybrid analyses. Deletion of selected vapC or vapBC genes did not affect mycobacterial growth in vitro, but rendered the organisms more susceptible to growth inhibition following toxic VapC expression. However, toxicity of 'non-toxic' VapCs was not unveiled in deletion mutant strains, even when the mutation eliminated the corresponding cognate VapB, presumably due to insufficient levels of VapC protein. Together with the ribonuclease (RNase activity demonstrated for Rv0065 and Rv0617--VapC proteins with similarity to Rv0549c and Rv3320c, respectively--these results suggest that the VapBC family potentially provides an abundant source of RNase activity in Mtb, which may profoundly impact the physiology of the organism.

  13. Immune disorders in hemodialysis patients.

    Science.gov (United States)

    Sharif, Mohammad Reza; Chitsazian, Zahra; Moosavian, Mehdi; Raygan, Fariba; Nikoueinejad, Hassan; Sharif, Ali Reza; Einollahi, Behzad

    2015-03-01

    Immunologically, End Stage renal Disease (ESRD) is associated with some disorders in both innate and adaptive immune system in such a form that there is a coexistence of both immune activation and immune suppression. Although these disorders are complex yet thoroughly unknown, there is a close relation between the progressively defective immune system with side effects as well as mortality causes including cardiovascular problems, infections, and malignancies. From the other point, chronic inflammation as a major determinant of "dialysis syndrome" (including malnutrition, cachexia, and vasculopathy) is considered as the main factor of inability and mortality in dialysis patients. Such inflammation is generally arisen from immune system response to uremia and individual's repetitive contact with dialysis instruments and, in the long term, leads to premature aging via intensifying tissue degeneration. Therefore, the immune system is known as one of the most important therapeutic targets to reduce morbidity and mortality in uremic and dialysis patients.   This review addresses different aspects as well as mechanisms of immune system dysfunction and possible therapeutics in dialysis patients.

  14. Soluble Mediators Regulating Immunity in Early Life

    Directory of Open Access Journals (Sweden)

    Matthew Aaron Pettengill

    2014-09-01

    Full Text Available Soluble factors in blood plasma have a substantial impact on both the innate and adaptive immune responses. The complement system, antibodies, and antimicrobial proteins and peptides (APPs, can directly interact with potential pathogens, protecting against systemic infection. The extracellular environment also has a critical influence on immune cell maturation, activation, and effector functions, and many of the factors in plasma, including hormones, vitamins, and purines, have been shown to influence these processes for leukocytes of both the innate and adaptive immune systems. In this review we give particular consideration to soluble mediators in plasma for which age-dependent differences in abundance may influence the ontogeny of immune function.

  15. dlk1/FA1 regulates the function of human bone marrow mesenchymal stem cells by modulating gene expression of pro-inflammatory cytokines and immune response-related factors

    DEFF Research Database (Denmark)

    Abdallah, Basem M.; Boissy, Patrice; Tan, Qihua

    2007-01-01

    dlk1/FA1 (delta-like 1/fetal antigen-1) is a member of the epidermal growth factor-like homeotic protein family whose expression is known to modulate the differentiation signals of mesenchymal and hematopoietic stem cells in bone marrow. We have demonstrated previously that Dlk1 can maintain...... the human bone marrow mesenchymal stem cells (hMSC) in an undifferentiated state. To identify the molecular mechanisms underlying these effects, we compared the basal gene expression pattern in Dlk1-overexpressing hMSC cells (hMSC-dlk1) versus control hMSC (negative for Dlk1 expression) by using Affymetrix......, apoptosis, and cell adhesion. Also, addition of purified FA1 to hMSC up-regulated the same factors in a dose-dependent manner. As biological consequences of up-regulating these immune response-related factors, we showed that the inhibitory effects of dlk1 on osteoblast and adipocyte differentiation of h...

  16. Granulocyte-macrophage stimulating factor (GM-CSF increases circulating dendritic cells but does not abrogate suppression of adaptive cellular immunity in patients with metastatic colorectal cancer receiving chemotherapy

    Directory of Open Access Journals (Sweden)

    Martinez Micaela

    2012-01-01

    Full Text Available Abstract Background Advanced cancer and chemotherapy are both associated with immune system suppression. We initiated a clinical trial in patients receiving chemotherapy for metastatic colorectal cancer to determine if administration of GM-CSF in this setting was immunostimulatory. Methods Between June, 2003 and January, 2007, 20 patients were enrolled in a clinical trial (NCT00257322 in which they received 500 ug GM-CSF daily for 4 days starting 24 hours after each chemotherapy cycle. There were no toxicities or adverse events reported. Blood was obtained before chemotherapy/GM-CSF administration and 24 hours following the final dose of GM-CSF and evaluated for circulating dendritic cells and adaptive immune cellular subsets by flow cytometry. Peripheral blood mononuclear cell (PBMC expression of γ-interferon and T-bet transcription factor (Tbx21 by quantitative real-time PCR was performed as a measure of Th1 adaptive cellular immunity. Pre- and post-treatment (i.e., chemotherapy and GM-CSF samples were evaluable for 16 patients, ranging from 1 to 5 cycles (median 3 cycles, 6 biologic sample time points. Dendritic cells were defined as lineage (- and MHC class II high (+. Results 73% of patients had significant increases in circulating dendritic cells of ~3x for the overall group (5.8% to 13.6%, p = 0.02 and ~5x excluding non-responders (3.2% to 14.5%, p Tbx21 levels declined by 75% following each chemotherapy cycle despite administration of GM-CSF (p = 0.02. PBMC γ-interferon expression, however was unchanged. Conclusions This clinical trial confirms the suppressive effects of chemotherapy on Th1 cellular immunity in patients with metastatic colorectal cancer but demonstrates that mid-cycle administration of GM-CSF can significantly increase the proportion of circulating dendritic cells. As the role of dendritic cells in anti-tumor immunity becomes better defined, GM-CSF administration may provide a non-toxic intervention to augment this arm

  17. Immunity and immunization in elderly.

    Science.gov (United States)

    Bourée, Patrice

    2003-12-01

    As the average life expectancy increases, retired people want to travel. Five to 8% of travellers in tropical areas are old persons. Immune system suffers of old age as the other organs. The number and the functions of the T-lymphocytes decrease, but the B-lymphocytes are not altered. So, the response to the vaccinations is slower and lower in the elderly. Influenza is a great cause of death rate in old people. The seroconversion, after vaccine, is 50% from 60 to 70 years old, 31% from 70 to 80 years old, and only 11% after 80 years old. But in public health, the vaccination reduced the morbidity by 25%, admission to hospital by 20%, pneumonia by 50%, and mortality by 70%. Antipoliomyelitis vaccine is useful for travellers, as the vaccines against hepatitis and typhoid fever. Pneumococcal vaccine is effective in 60%. Tetanus is fatal in at last 32% of the people above 80 years, therefore this vaccine is very important.

  18. Innate immune response to viral infection.

    Science.gov (United States)

    Koyama, Shohei; Ishii, Ken J; Coban, Cevayir; Akira, Shizuo

    2008-09-01

    In viral infections the host innate immune system is meant to act as a first line defense to prevent viral invasion or replication before more specific protection by the adaptive immune system is generated. In the innate immune response, pattern recognition receptors (PRRs) are engaged to detect specific viral components such as viral RNA or DNA or viral intermediate products and to induce type I interferons (IFNs) and other pro-inflammatory cytokines in the infected cells and other immune cells. Recently these innate immune receptors and their unique downstream pathways have been identified. Here, we summarize their roles in the innate immune response to virus infection, discrimination between self and viral nucleic acids and inhibition by virulent factors and provide some recent advances in the coordination between innate and adaptive immune activation.

  19. Epithelial cells prime the immune response to an array of gut-derived commensals towards a tolerogenic phenotype through distinct actions of thymic stromal lymphopoietin and transforming growth factor-beta

    DEFF Research Database (Denmark)

    Zeuthen, Louise Hjerrild; Fink, Lisbeth Nielsen; Frøkiær, Hanne

    2007-01-01

    maintenance of the gut immune homeostasis. Here we report novel crosstalk mechanisms between the human enterocyte cell line, Caco2, and underlying human monocyte-derived DC in a transwell model where Gram-positive (G+) commensals prevent Toll-like receptor-4 (TLR4)-dependent Escherichia coli...... of maturation markers, interleukin (IL)-12p70, and tumour necrosis factor-alpha when matured with G+ and Gram-negative (G-) commensals, while IL-10 production is enhanced in DC upon encountering G+ commensals and reduced upon encountering G- bacteria. The Caco2 SM-induced tolerogenic phenotype is also seen...

  20. Study of immunization coverage and influence factors of left-behind children in rural areas of Chongqing%重庆市农村留守儿童预防接种现状与影响因素分析

    Institute of Scientific and Technical Information of China (English)

    徐佳薇; 姚宁; 匡珊珊; 王青

    2015-01-01

    Objective To investigate the immunization coverage and its influence factors of left-behind children in rural areas of Chongqing, and explore intervening measures. Methods 1 441 complete questionnaires were obtained by surveying the custodians of 1 year old left-behind/non left-behind children in 3 counties;immunization difference and influence factors were statistically analyzed. Results Besides BCG and the former two doses of hepatitis B vaccine, non-left-behind children all have statistically higher coverage than left-behind children of the 7 vaccines in immunization program targeted 1 year age group. Parents as guardians, non-left-behind children and the guardians knew children′s inoculation schedule were the positive factors to children′s inoculation rate. Conclusion Grandfather or grandmother as the guardians of left-behind children were with low education level, and their poor awareness of immunization knowledge and inoculation schedule are the main influence factor to vaccination coverage of the left-behind children in rural area.%目的:了解重庆市农村留守儿童的免疫状况及其影响因素,探索相应的干预政策。方法对3个项目县的1441名1岁组留守/非留守儿童监护人进行问卷调查,并查验儿童接种证获取信息,分析儿童接种率差异和影响因素。结果除卡介苗和乙肝前两剂次外,各项基础免疫疫苗非留守儿童接种率均高于留守儿童,差异有统计学意义(P<0.05)。监护人为父母、非留守、监护人对接种时间知晓是影响儿童接种的保护因素。结论留守儿童的监护人主要为文化程度较低的(外)祖父母,他们对预防接种知识的掌握以及监护人的性质成为了影响儿童接种率的主要原因。

  1. Immune System Quiz

    Science.gov (United States)

    ... Know About Puberty Train Your Temper Quiz: Immune System KidsHealth > For Kids > Quiz: Immune System Print A A A How much do you know about your immune system? Find out by taking this quiz! About KidsHealth ...

  2. The structure of a contact-dependent growth-inhibition (CDI) immunity protein from Neisseria meningitidis MC58

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Kemin; Johnson, Parker M.; Stols, Lucy; Boubion, Bryan; Eschenfeldt, William; Babnigg, Gyorgy; Hayes, Christopher S.; Joachimiak, Andrzej; Goulding, Celia W.

    2015-06-01

    Contact-dependent growth inhibition (CDI) is an important mechanism of intercellular competition between neighboring Gram-negative bacteria. CDI systems encode large surface-exposed CdiA effector proteins that carry a variety of C-terminal toxin domains (CdiA-CTs). All CDI+ bacteria also produce CdiI immunity proteins that specifically bind to the cognate CdiA-CT and neutralize its toxin activity to prevent auto-inhibition. Here, the X-ray crystal structure of a CdiI immunity protein from Neisseria meningitidis MC58 is presented at 1.45 angstrom resolution. The CdiI protein has structural homology to the Whirly family of RNA-binding proteins, but appears to lack the characteristic nucleic acid-binding motif of this family. Sequence homology suggests that the cognate CdiA-CT is related to the eukaryotic EndoU family of RNA-processing enzymes. A homology model is presented of the CdiA-CT based on the structure of the XendoU nuclease from Xenopus laevis. Molecular-docking simulations predict that the CdiA-CT toxin active site is occluded upon binding to the CdiI immunity protein. Together, these observations suggest that the immunity protein neutralizes toxin activity by preventing access to RNA substrates.

  3. MICROECOLOGY OF NASOPHARYNGEAL MUCOSAL MEMBRANES AND ESTIMATION OF FACTORS OF MUCOSAL AND LYMPHOCYTIC IMMUNITY IN RECRUITS DURING THE FORMATION OF ORGANIZED TEAM

    Directory of Open Access Journals (Sweden)

    V. A. Nikiforov

    2014-01-01

    Full Text Available Contamination of nasopharyngeal mucosa by opportunistic and pathogenic bacteria in practically healthy people during the formation of the close group has been accompanied by a dysfunction of mucosal immunity, imbalanceof cytokine profile, insolvency of antioxidant system, increasing endointoxication. Adequate changes of serum immunoglobulins level in patients with nasopharyngeal dysbiosis allow to conclude of usefulness of the pre-emptive vaccination and using drugs with immunomodulatory effect which reliably satisfy body’s need for antioxidants.

  4. Boar taint, meat quality and fail rate in entire male pigs and male pigs immunized against gonadotrophin releasing factor as related to body weight and feeding regime.

    Science.gov (United States)

    Moore, K L; Mullan, B P; Dunshea, F R

    2017-03-01

    The objective of this experiment was to compare the pork quality of entire male pigs and pigs immunized against GnRF (IC males) at both light (64.8kg) and heavy (106kg) liveweights and two feeding regimes (restricted at 2.5 times maintenance and ad libitum). There was no difference in objective measurements (P>0.05) or eating pork quality (P>0.1) between entire male and IC males. Fail rates were reduced by 9.1% and 12% for pork from IC males for quality grade (P=0.007) and re-purchase intention (P=0.001), respectively, compared to pork from entire males. Skatole (P=0.001) and androstenone (P<0.001) levels in belly fat were higher in entire male than IC male pigs. In addition, 37.5% of the light entire male pigs fed ad libitum showed skatole levels that exceeded the sensory threshold of 0.2μg/g. This work confirms that immunization against GnRF is effective in eliminating boar taint and reducing pork quality fail rates by approximately 10% compared to pork from entire males.

  5. Ribosome-induced changes in elongation factor Tu conformation control GTP hydrolysis

    DEFF Research Database (Denmark)

    Villa, Elizabeth; Sengupta, Jayati; Trabuco, Leonard G.

    2009-01-01

    In translation, elongation factor Tu (EF-Tu) molecules deliver aminoacyl-tRNAs to the mRNA-programmed ribosome. The GTPase activity of EF-Tu is triggered by ribosome-induced conformational changes of the factor that play a pivotal role in the selection of the cognate aminoacyl-tRNAs. We present a...

  6. Yersinia pestis YopJ suppresses tumor necrosis factor alpha induction and contributes to apoptosis of immune cells in the lymph node but is not required for virulence in a rat model of bubonic plague.

    Science.gov (United States)

    Lemaître, Nadine; Sebbane, Florent; Long, Daniel; Hinnebusch, B Joseph

    2006-09-01

    The virulence of the pathogenic Yersinia species depends on a plasmid-encoded type III secretion system that transfers six Yop effector proteins into host cells. One of these proteins, YopJ, has been shown to disrupt host cell signaling pathways involved in proinflammatory cytokine production and to induce macrophage apoptosis in vitro. YopJ-dependent apoptosis in mesenteric lymph nodes has also been demonstrated in a mouse model of Yersinia pseudotuberculosis infection. These results suggest that YopJ attenuates the host innate and adaptive immune response during infection, but the role of YopJ during bubonic plague has not been completely established. We evaluated the role of Yersinia pestis YopJ in a rat model of bubonic plague following intradermal infection with a fully virulent Y. pestis strain and an isogenic yopJ mutant. Deletion of yopJ resulted in a twofold decrease in the number of apoptotic immune cells in the bubo and a threefold increase in serum tumor necrosis factor alpha levels but did not result in decreased virulence, systemic spread, or colonization levels in the spleen and blood. Our results indicate that YopJ is not essential for bubonic plague pathogenesis, even after peripheral inoculation of low doses of Y. pestis. Instead, the effects of YopJ appear to overlap and augment the immunomodulatory effects of other Y. pestis virulence factors.

  7. 嗜肺军团菌主要毒力因子与细胞免疫反应%Major virulence factors of legionella pneumophila and cell immune response

    Institute of Scientific and Technical Information of China (English)

    严慧; 朱庆义

    2014-01-01

    Legionella pneumophila (L. pneumophila) is an intracellular pathogen, it is a common cause of community-acquired respiratory tract infections and an occasional cause of nosocomial pneumonia. The pathogenicity is closely related to its virulence factors. The main protective role was played by the cellular responses after L. pneumophila infection. The Dot/IcmⅣ type secretion system is the main virulence factor of L. pneumophila, secretes a large number of effector proteins into infected cells. These effectors activate immune regulator factors like NF-κB, and mediated the L. pneumophila intracellular growth and replication. The other main virulence factors, such as Mip, flagellin and LPS, are referred to its infection and reproductive capacity, and play an important role in the cell immune response. This review will focus on the interactions between the major virulence factors of L. pneumophila and its pathogenicity, and discuss implications for the study of the immune detection mechanisms.%嗜肺军团菌是胞内的寄生菌,主要以细胞免疫为主,是引起社区获得性和医院内感染性肺炎的重要病原体,其致病性与毒力因子密切相关。Dot/IcmⅣ分泌系统是嗜肺军团菌的重要毒力因子,能诱发大量底物效应蛋白,激活免疫调控因子如NF-κB,调控嗜肺军团菌细胞内的生长繁殖。该细菌表面主要毒力因子如Mip蛋白、鞭毛蛋白和LPS脂多糖等,与嗜肺军团菌侵染和繁殖能力有关,在细胞免疫反应中具有重要作用。本文简要概述了嗜肺军团菌几个主要毒力因子、致病性以及与寄主免疫之间的相互关系。

  8. Dietary myo-inositol modulates immunity through antioxidant activity and the Nrf2 and E2F4/cyclin signalling factors in the head kidney and spleen following infection of juvenile fish with Aeromonas hydrophila.

    Science.gov (United States)

    Jiang, Wei-Dan; Hu, Kai; Liu, Yang; Jiang, Jun; Wu, Pei; Zhao, Juan; Zhang, Yong-An; Zhou, Xiao-Qiu; Feng, Lin

    2016-02-01

    This study was conducted to investigate the effects of the dietary vitamin myo-inositol (MI), on the immunity and structural integrity of the head kidney and spleen following infection of fish with the major freshwater pathogen bacterial Aeromonas hydrophila. The results demonstrated for the first time that MI deficiency depressed the lysozyme and acid phosphatase (ACP) activities and the complement 3 (C3) and C4 contents in the head kidney and spleen compared with the optimal MI levels, indicating that MI deficiency decreased the immunity of these important fish immune organs. The depression in immunity due to MI deficiency was partially related to oxidative damage [indicated by increases in the malondialdehyde (MDA) and protein carbonyl (PC) contents] that was in turn partially due to the decreased glutathione (GSH) content and the disturbances in antioxidant enzyme activities [total superoxide dismutase (T-SOD), CuZnSOD, MnSOD, catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR)]. MI deficiency inhibited the antioxidant-related gene transcription [CuZnSOD, MnSOD, CAT, GPx1a, GR and NF-E2-related factor 2 (Nrf2)] in the head kidney and spleen following infection of the fish with A. hydrophila. The oxidative damage due to MI deficiency also resulted in the inhibition of proliferation-associated signalling (cyclin D1, cyclin A, cyclin E and E2F4). Thus, MI deficiency partially inhibited damage repair. Excessive MI exhibited negative effects that were similar to MI deficiency, whereas the optimal MI content reversed those indicators. These observations indicated that an MI deficiency or excess could cause depression of the immune system that might be partially related to oxidative damage, antioxidant disturbances, and the inhibition of the proliferation-associated signalling in the head kidney and spleen following infection of fish with A. hydrophila. Finally, the optimal MI levels were 660.7 (based on ACP) and 736.8 mg kg(-1) diet (based

  9. 从同源词的孳乳看词源意义的运动%The Movement of the Etymological Meaning Seen from the Evolution of Cognate Words

    Institute of Scientific and Technical Information of China (English)

    陈昌琳; 孙品健

    2011-01-01

    从认知和心理的角度,按照相似联想、对比联想和接近联想对同源词孳乳的不同作用,描述同源词孳乳的动态过程,从中观察词源意义的运动,总结出同源词孳乳过程中三种词源意义的运动形式。%At the level of the cognitive psychology, and according to the influences on the Evolution of Cognate Words caused by the similarity association, the contrast association and the contiguity association, the paper describes the dynamic process of the Evolution of Cognate Words and the movement of the etymological meaning and summarizes three forms of the movement of the etymological meaning in the Evolution of Cognate Words.

  10. The immune consequences of preterm birth

    Directory of Open Access Journals (Sweden)

    Jacqueline M Melville

    2013-05-01

    Full Text Available Preterm birth occurs in 11% of live births globally and accounts for 35% of all newborn deaths. Preterm newborns have immature immune systems, with reduced innate and adaptive immunity; their immune systems may be further compromised by various factors associated with preterm birth.The immune systems of preterm infants have a smaller pool of monocytes and neutrophils, impaired ability of these cells to kill pathogens, and lower production of cytokines which limits T cell activation and reduces the ability to fight bacteria and detect viruses in cells, compared to term infants.Intrauterine inflammation is a major contributor to preterm birth, and causes premature immune activation and cytokine production. This can induce immune tolerance leading to reduced newborn immune function. Intrauterine inflammation is associated with an increased risk of early-onset sepsis and likely has long-term adverse immune consequences.Requisite medical interventions further impact on immune development and function. Antenatal corticosteroid treatment to prevent newborn respiratory disease is routine but may be immunosuppressive, and has been associated with febrile responses, reductions in lymphocyte proliferation and cytokine production, and increased risk of infection. Invasive medical procedures result in an increased risk of late-onset sepsis. Respiratory support can cause chronic inflammatory lung disease associated with increased risk of long-term morbidity.Colonisation of the infant by microorganisms at birth is a significant contributor to the establishment of the microbiome. Caesarean section affects infant colonisation, potentially contributing to lifelong immune function and wellbeing.Several factors associated with preterm birth alter immune function. A better understanding of perinatal modification of the preterm immune system will allow for the refinement of care to minimise lifelong adverse immune consequences.

  11. Pasteurella multocida and immune cells.

    Science.gov (United States)

    Kubatzky, Katharina F

    2012-01-01

    Pasteurella multocida was first discovered by Perroncito in 1878 and named after Louis Pasteur who first isolated and described this Gram-negative bacterium as the cause of fowl disease in 1880. Subsequently, P. multocida was also found to cause atrophic rhinitis in pigs, haemorrhagic septicaemia in cattle and respiratory diseases in many other animals. Among other factors such as lipopolysaccharide, outer membrane proteins and its capsule, the protein toxin (PMT) of P. multocida is an important virulence factor that determines the immunological response of the host's immune system. However, the exact molecular mechanisms taking place in cells of the innate and adaptive immune system are largely unknown for any of these virulence factors. Due to the obvious function of PMT on cells of the porcine skeletal system where it causes bone destruction, PMT was regarded as an osteolytic protein toxin. However, it remained unclear what the actual benefit for the bacteria would be. Recently, more attention was drawn to the osteoimmunological effects of PMT and the interplay between bone and immune cells. This review summarises the knowledge of effects of P. multocida virulence factors on the host's immune system.

  12. Immune response to fungal infections.

    Science.gov (United States)

    Blanco, Jose L; Garcia, Marta E

    2008-09-15

    The immune mechanisms of defence against fungal infections are numerous, and range from protective mechanisms that were present early in evolution (innate immunity) to sophisticated adaptive mechanisms that are induced specifically during infection and disease (adaptive immunity). The first-line innate mechanism is the presence of physical barriers in the form of skin and mucous membranes, which is complemented by cell membranes, cellular receptors and humoral factors. There has been a debate about the relative contribution of humoral and cellular immunity to host defence against fungal infections. For a long time it was considered that cell-mediated immunity (CMI) was important, but humoral immunity had little or no role. However, it is accepted now that CMI is the main mechanism of defence, but that certain types of antibody response are protective. In general, Th1-type CMI is required for clearance of a fungal infection, while Th2 immunity usually results in susceptibility to infection. Aspergillosis, which is a disease caused by the fungus Aspergillus, has been the subject of many studies, including details of the immune response. Attempts to relate aspergillosis to some form of immunosuppression in animals, as is the case with humans, have not been successful to date. The defence against Aspergillus is based on recognition of the pathogen, a rapidly deployed and highly effective innate effector phase, and a delayed but robust adaptive effector phase. Candida albicans, part of the normal microbial flora associated with mucous surfaces, can be present as congenital candidiasis or as acquired defects of cell-mediated immunity. Resistance to this yeast is associated with Th1 CMI, whereas Th2 immunity is associated with susceptibility to systemic infection. Dermatophytes produce skin alterations in humans and other animals, and the essential role of the CMI response is to destroy the fungi and produce an immunoprotective status against re-infection. The resolution

  13. Understanding Herd Immunity.

    Science.gov (United States)

    Metcalf, C J E; Ferrari, M; Graham, A L; Grenfell, B T

    2015-12-01

    Individual immunity is a powerful force affecting host health and pathogen evolution. Importantly, the effects of individual immunity also scale up to affect pathogen transmission dynamics and the success of vaccination campaigns for entire host populations. Population-scale immunity is often termed 'herd immunity'. Here we outline how individual immunity maps to population outcomes and discuss implications for control of infectious diseases. Particular immunological characteristics may be more or less likely to result in a population level signature of herd immunity; we detail this and also discuss other population-level outcomes that might emerge from individual-level immunity.

  14. Macrophage Migration Inhibitory Factor (MIF) of the protozoan parasite Eimeria influences the components of the immune system of its host, the chicken

    Science.gov (United States)

    Macrophage migration inhibitory factor (MIF) is a soluble factor produced by sensitized T lymphocytes that inhibits the random migration of macrophages. Homologues of MIF from invertebrates have been identified making it an interesting molecule from a functional perspective. In the present study, ...

  15. Feeding Our Immune System: Impact on Metabolism

    Directory of Open Access Journals (Sweden)

    Isabelle Wolowczuk

    2008-01-01

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

  16. Immune regulation of ovarian development: programming by neonatal immune challenge

    Directory of Open Access Journals (Sweden)

    Luba eSominsky

    2013-06-01

    Full Text Available Neonatal immune challenge by administration of lipopolysaccharide (LPS produces enduring alterations in the development and activity of neuroendocrine, immune and other physiological systems. We have recently reported that neonatal exposure to an immune challenge by administration of LPS results in altered reproductive development in the female Wistar rat. Specifically, LPS-treated animals exhibited diminished ovarian reserve and altered reproductive lifespan. In the current study, we examined the cellular mechanisms that lead to the previously documented impaired ovulation and reduced follicular pool. Rats were administered intraperitoneally either 0.05mg/kg of LPS (Salmonella Enteritidis or an equivalent volume of non-pyrogenic saline on postnatal days (PNDs 3 and 5, and ovaries were obtained on PND 7. Microarray analysis revealed a significant upregulation in transcript expression (2-fold change; p<.05 for a substantial number of genes in the ovaries of LPS-treated animals, implicated in immune cell signalling, inflammatory responses, reproductive system development and disease. Several canonical pathways involved in immune recognition were affected by LPS treatment, such as nuclear factor-κB (NF-kB activation and LPS-stimulated mitogen-activated protein kinase (MAPK signalling. Real-time PCR analysis supported the microarray results. Protein expression analysis of several components of the MAPK signalling pathway revealed a significant upregulation in the expression of Toll-like receptor 4 (TLR4 in the neonatal ovary of LPS-treated animals. These results indicate that neonatal immune challenge by administration of LPS has a direct effect on the ovary during the sensitive period of follicular formation. Given the pivotal role of inflammatory processes in the regulation of reproductive health, our findings suggest that early life immune activation via TLR signalling may have significant implications for the programming of ovarian development

  17. Factor interaction analysis for chromosome 8 and DNA methylation alterations highlights innate immune response suppression and cytoskeletal changes in prostate cancer

    Directory of Open Access Journals (Sweden)

    Lengauer Thomas

    2007-02-01

    Full Text Available Abstract Background Alterations of chromosome 8 and hypomethylation of LINE-1 retrotransposons are common alterations in advanced prostate carcinoma. In a former study including many metastatic cases, they strongly correlated with each other. To elucidate a possible interaction between the two alterations, we investigated their relationship in less advanced prostate cancers. Results In 50 primary tumor tissues, no correlation was observed between chromosome 8 alterations determined by comparative genomic hybridization and LINE-1 hypomethylation measured by Southern blot hybridization. The discrepancy towards the former study, which had been dominated by advanced stage cases, suggests that both alterations converge and interact during prostate cancer progression. Therefore, interaction analysis was performed on microarray-based expression profiles of cancers harboring both alterations, only one, or none. Application of a novel bioinformatic method identified Gene Ontology (GO groups related to innate immunity, cytoskeletal organization and cell adhesion as common targets of both alterations. Many genes targeted by their interaction were involved in type I and II interferon signaling and several were functionally related to hereditary prostate cancer genes. In addition, the interaction appeared to influence a switch in the expression pattern of EPB41L genes encoding 4.1 cytoskeleton proteins. Real-time RT-PCR revealed GADD45A, MX1, EPB41L3/DAL1, and FBLN1 as generally downregulated in prostate cancer, whereas HOXB13 and EPB41L4B were upregulated. TLR3 was downregulated in a subset of the cases and associated with recurrence. Downregulation of EPB41L3, but not of GADD45A, was associated with promoter hypermethylation, which was detected in 79% of carcinoma samples. Conclusion Alterations of chromosome 8 and DNA hypomethylation in prostate cancer probably do not cause each other, but converge during progression. The present analysis implicates their

  18. SLAP deficiency increases TCR avidity leading to altered repertoire and negative selection of cognate antigen-specific CD8+ T cells.

    Science.gov (United States)

    Friend, Samantha F; Peterson, Lisa K; Kedl, Ross M; Dragone, Leonard L

    2013-03-01

    How T cell receptor (TCR) avidity influences CD8(+) T cell development and repertoire selection is not yet fully understood. To fill this gap, we utilized Src-like adaptor protein (SLAP)-deficient mice as a tool to increase TCR avidity on double positive (DP) thymocytes. We generated SLAP(-/-) mice with the transgenic MHC class I-restricted TCR (OT-1) and SLAP(-/-) Vβ5 mice, expressing only the β-chain of the TCR OT-1 transgene, to examine the effects of increased TCR surface levels on CD8(+) T cell development and repertoire selection. In comparing SLAP(-/-) OT-1 and Vβ5 mice with wild-type controls, we performed compositional analysis and assessed thymocyte signaling by measuring CD5 levels. In addition, we performed tetramer and compositional staining to measure affinity for the cognate antigen, ovalbumin (OVA) peptide, presented by MHC. Furthermore, we quantified differences in α-chain repertoire in SLAP(-/-) Vβ5 mice. We have found that SLAP(-/-) OT-1 mice have fewer CD8(+) thymocytes but have increased CD5 expression. SLAP(-/-) OT-1 mice have fewer DP thymocytes expressing Vα2, signifying increased endogenous α-chain rearrangement, and more non-OVA-specific CD8(+) splenocytes upon tetramer staining. Our data demonstrate that SLAP(-/-) Vβ5 mice also have fewer OVA-specific cells and increased Vα2 usage in the peripheral Vβ5 CD8(+) T cells that were non-OVA-specific, demonstrating differences in α-chain repertoire. These studies provide direct evidence that increased TCR avidity in DP thymocytes enhances CD8(+) T cell negative selection deleting thymocytes with specificity for cognate antigen, an antigen the mature T cells may never encounter. Collectively, these studies provide new insights into how TCR avidity during CD8(+) T cell development influences repertoire selection.

  19. Immune response of rainbow trout (Oncorhynchus mykiss) larvae to Yersinia ruckeri

    DEFF Research Database (Denmark)

    Chettri, Jiwan Kumar; Kania, Per Walter; Raida, Martin Kristian

    Innate immune factors play a crucial role in survival of young fish especially during early stages of life where adaptive immunity is not fully developed. In the present study, we investigated the immune response of rainbow trout larvae (Onchorhynchus mykiss) at an early stage of development. We...... of immune factors at the transcriptional level. It may be speculated that at this stage of life, larvae may combat invading pathogens by using armour consisting of different immune factors without regulating their expression....

  20. Female versus male biological identities of nanoparticles determine the interaction with immune cells in fish

    DEFF Research Database (Denmark)

    Hayashi, Yuya; Miclaus, Teodora; Murugadoss, Sivakumar

    2017-01-01

    can acquire a differential biological identity. Here we examined whether a unique biological identity acquired from sex-specific protein repertoires could alter the degree of nanoparticle uptake by cognate immune cells. We chose zebrafish as a model species of which blood plasma is sexually contrasted......, a “female” biological identity of the nanoparticles was represented by prevailing contribution of vitellogenins to the corona proteome. We then exposed zebrafish blood cells to the three types of pre-formed nanoparticle–protein complexes and compared nanoparticle uptake using flow cytometry. Lymphoid...

  1. Pathogen effectors target Arabidopsis EDS1 and alter its interactions with immune regulators.

    Science.gov (United States)

    Bhattacharjee, Saikat; Halane, Morgan K; Kim, Sang Hee; Gassmann, Walter

    2011-12-01

    Plant resistance proteins detect the presence of specific pathogen effectors and initiate effector-triggered immunity. Few immune regulators downstream of resistance proteins have been identified, none of which are known virulence targets of effectors. We show that Arabidopsis ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1), a positive regulator of basal resistance and of effector-triggered immunity specifically mediated by Toll-interleukin-1 receptor-nucleotide binding-leucine-rich repeat (TIR-NB-LRR) resistance proteins, forms protein complexes with the TIR-NB-LRR disease resistance proteins RPS4 and RPS6 and with the negative immune regulator SRFR1 at a cytoplasmic membrane. Further, the cognate bacterial effectors AvrRps4 and HopA1 disrupt these EDS1 complexes. Tight association of EDS1 with TIR-NB-LRR-mediated immunity may therefore derive mainly from being guarded by TIR-NB-LRR proteins, and activation of this branch of effector-triggered immunity may directly connect to the basal resistance signaling pathway via EDS1.

  2. Target motifs affecting natural immunity by a constitutive CRISPR-Cas system in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Cristóbal Almendros

    Full Text Available Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR and CRISPR associated (cas genes conform the CRISPR-Cas systems of various bacteria and archaea and produce degradation of invading nucleic acids containing sequences (protospacers that are complementary to repeat intervening spacers. It has been demonstrated that the base sequence identity of a protospacer with the cognate spacer and the presence of a protospacer adjacent motif (PAM influence CRISPR-mediated interference efficiency. By using an original transformation assay with plasmids targeted by a resident spacer here we show that natural CRISPR-mediated immunity against invading DNA occurs in wild type Escherichia coli. Unexpectedly, the strongest activity is observed with protospacer adjoining nucleotides (interference motifs that differ from the PAM both in sequence and location. Hence, our results document for the first time native CRISPR activity in E. coli and demonstrate that positions next to the PAM in invading DNA influence their recognition and degradation by these prokaryotic immune systems.

  3. Vaccination with DNA encoding truncated enterohemorrhagic Escherichia coli (EHEC factor for adherence-1 gene (efa-1’ confers protective immunity to mice infected with E. coli O157:H7

    Directory of Open Access Journals (Sweden)

    Roberto eRiquelme-Neira

    2016-01-01

    Full Text Available Enterohemorrhagic Escherichia coli (EHEC O157:H7 is the predominant causative agent of hemorrhagic colitis in humans and is the cause of haemolytic uraemic syndrome and other illnesses. Cattle have been implicated as the main reservoir of this organism. Here, we evaluated the immunogenicity and protective efficacy of a DNA vaccine encoding conserved sequences of truncated EHEC factor for adherence-1 (efa-1’ in a mouse model. Intranasal administration of plasmid DNA carrying the efa-1’ gene (pVAXefa-1’ into C57BL/6 mice elicited both humoral and cellular immune responses. In animals immunized with pVAXefa-1`, EHEC-secreted protein-specific IgM and IgG antibodies were detected in sera at day 45. Anti-EHEC-secreted protein sIgA was also detected in nasal and bronchoalveolar lavages. In addition, antigen-specific T-cell-proliferation, IL-10 and IFN-γ were observed upon re-stimulation with either heat-killed bacteria or EHEC-secreted proteins. Vaccinated animals were also protected against challenge with E. coli O157:H7 strain EDL933. These results suggest that DNA vaccine encoding efa-1´ have therapeutic potential in interventions against EHEC infections. This approach could lead to a new strategy in the production of vaccines that prevent infections in cattle.

  4. Immune-enhancing effect of nano-DNA vaccine encoding a gene of the prME protein of Japanese encephalitis virus and BALB/c mouse granulocyte-macrophage colony-stimulating factor.

    Science.gov (United States)

    Zhai, Yongzhen; Zhou, Yan; Li, Ximei; Feng, Guohe

    2015-07-01

    Plasmid-encoded granulocyte-macrophage colony-stimulating factor (GM‑CSF) is an adjuvant for genetic vaccines; however, how GM-CSF enhances immunogenicity remains to be elucidated. In the present study, it was demonstrated that injection of a plasmid encoding the premembrane (prM) and envelope (E) protein of Japanese encephalitis virus and mouse GM-CSF (pJME/GM-CSF) into mouse muscle recruited large and multifocal conglomerates of macrophages and granulocytes, predominantly neutrophils. During the peak of the infiltration, an appreciable number of immature dendritic cells (DCs) appeared, although no T and B-cells was detected. pJME/GM-CSF increased the number of splenic DCs and the expression of major histocompatibility complex class II (MHCII) on splenic DC, and enhanced the antigenic capture, processing and presentation functions of splenic DCs, and the cell-mediated immunity induced by the vaccine. These findings suggested that the immune-enhancing effect by pJME/GM-CSF was associated with infiltrate size and the appearance of integrin αx (CD11c)+cells. Chitosan-pJME/GM-CSF nanoparticles, prepared by coacervation via intramuscular injection, outperformed standard pJME/GM-CSF administrations in DC recruitment, antigen processing and presentation, and vaccine enhancement. This revealed that muscular injection of chitosan‑pJME/GM-CSF nanoparticles may enhance the immunoadjuvant properties of GM-CSF.

  5. Vaccination with DNA Encoding Truncated Enterohemorrhagic Escherichia coli (EHEC) Factor for Adherence-1 Gene (efa-1') Confers Protective Immunity to Mice Infected with E. coli O157:H7.

    Science.gov (United States)

    Riquelme-Neira, Roberto; Rivera, Alejandra; Sáez, Darwin; Fernández, Pablo; Osorio, Gonzalo; del Canto, Felipe; Salazar, Juan C; Vidal, Roberto M; Oñate, Angel

    2015-01-01

    Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is the predominant causative agent of hemorrhagic colitis in humans and is the cause of haemolytic uraemic syndrome and other illnesses. Cattle have been implicated as the main reservoir of this organism. Here, we evaluated the immunogenicity and protective efficacy of a DNA vaccine encoding conserved sequences of truncated EHEC factor for adherence-1 (efa-1') in a mouse model. Intranasal administration of plasmid DNA carrying the efa-1' gene (pVAXefa-1') into C57BL/6 mice elicited both humoral and cellular immune responses. In animals immunized with pVAXefa-1', EHEC-secreted protein-specific IgM and IgG antibodies were detected in sera at day 45. Anti-EHEC-secreted protein sIgA was also detected in nasal and bronchoalveolar lavages. In addition, antigen-specific T-cell-proliferation, IL-10, and IFN-γ were observed upon re-stimulation with either heat-killed bacteria or EHEC-secreted proteins. Vaccinated animals were also protected against challenge with E. coli O157:H7 strain EDL933. These results suggest that DNA vaccine encoding efa-1' have therapeutic potential in interventions against EHEC infections. This approach could lead to a new strategy in the production of vaccines that prevent infections in cattle.

  6. Determinants of immunization coverage in Lucknow district

    Directory of Open Access Journals (Sweden)

    Pratibha Gupta

    2015-01-01

    Full Text Available Background: Immunization remains one of the most important public health interventions and a cost-effective strategy to reduce both the morbidity and mortality associated with infectious diseases. Over two million deaths are delayed through immunization each year worldwide. Aims: This study sought to identify specific factors associated with immunization coverage in order to advance improved intervention, policies/strategies therefore raising overall immunization coverage. Materials and Methods: A cross-sectional study was conducted among a total of 198 children aged 12-23 months at Urban Health and Training Centre (UHTC, Era′s Lucknow Medical College, Lucknow, over a period of 6 months i.e., from July 2012-December 2012. Data were collected, compiled and tabulated using Microsoft Excel and analyzed using SPSS 17.0 version. Results: A total of 198 children of age 12-23 months were included in this study, of which 74.7% of children were fully immunized, 11.1% were partially immunized and 14.1% were not immunized at all. The most common reason for partial or non-immunization was family problems (24% of the respondents followed by lack of knowledge of immunization (20%, and fear of side effects (16%. The odds of risk of partial/non-immunization in illiterate women is 5.78 more than the graduate women (P = 0.039. Conclusions: Although in the present study, majority of the children were immunized, it is still not up to the mark. We have to make it 100%, so that we can reduce mortality due to vaccine-preventable diseases. Increasing awareness and reducing fear of side effects of immunization among parents through health education, counseling, etc. can increase the percentage of immunized children.

  7. Identification of HIV-1 Epitopes that Induce the Synthesis of a R5 HIV-1 Suppression Factor by Human CD4+ T Cells Isolated from HIV-1 Immunized Hu-PBL SCID Mice

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    Atsushi Yoshida

    2005-01-01

    Full Text Available We have previously reported that immunization of the severe combined immunodeficiency (SCID mice reconstituted with human peripheral blood mononuclear cells (PBMC (hu-PBL-SCID mice with inactivated human immunodeficiency virus type-1 (HIV-1-pulsed-autologous dendritic cells (HIV-DC elicits HIV-1-reactive CD4+ T cells that produce an as yet to be defined novel soluble factor in vitro with anti-viral properties against CCR5 tropic (R5 HIV-1 infection. These findings led us to perform studies designed to identify the lineage of the cell that synthesizes such a factor in vitro and define the epitopes of HIV-1 protein that have specificity for the induction of such anti-viral factor. Results of our studies show that this property is a function of CD4+ but not CD8+ T cells. Human CD4+ T cells were thus recovered from the HIV-DC-immunized hu-PBL-SCID mice and were re-stimulated in vitro by co-culture for 2 days with autologous adherent PBMC as antigen presenting cells, APC previously pulsed with inactivated HIV in IL-2-containing medium to expand HIV-1-reactive CD4+ T cells. Aliquots of these re-stimulated CD4+ T cells were then co-cultured with similar APC's that were previously pulsed with 10 μg/ml of a panel of HIV peptides for an additional 2 days, and their culture supernatants were examined for the production of both the R5 HIV-1 suppression factor and IFN-Υ. The data presented herein show that the HIV-1 primed CD4+ T cells produced the R5 suppression factor in response to a wide variety of HIV-1 gag, env, pol, nef or vif peptides, depending on the donor of the CD4+ T cells. Simultaneous production of human interferon (IFN-Υ was observed in some cases. These results indicate that human CD4+ T cells in PBMC of HIV-1 naive donors have a wide variety of HIV-1 epitope-specific CD4+ T cell precursors that are capable of producing the R5 HIV-1 suppression factor upon DC-based vaccination with whole inactivated HIV-1.

  8. Identification of HIV-1 epitopes that induce the synthesis of a R5 HIV-1 suppression factor by human CD4+ T cells isolated from HIV-1 immunized hu-PBL SCID mice.

    Science.gov (United States)

    Yoshida, Atsushi; Tanaka, Reiko; Kodama, Akira; Yamamoto, Naoki; Ansari, Aftab A; Tanaka, Yuetsu

    2005-12-01

    We have previously reported that immunization of the severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood mononuclear cells (PBMC) (hu-PBL-SCID mice) with inactivated human immunodeficiency virus type-1 (HIV-1)-pulsed-autologous dendritic cells (HIV-DC) elicits HIV-1-reactive CD4(+) T cells that produce an as yet to be defined novel soluble factor in vitro with anti-viral properties against CCR5 tropic (R5) HIV-1 infection. These findings led us to perform studies designed to identify the lineage of the cell that synthesizes such a factor in vivo and define the epitopes of HIV-1 protein that have specificity for the induction of such anti-viral factor. Results of our studies show that this property is a function of CD4(+) but not CD8(+) T cells. Human CD4(+) T cells were thus recovered from the HIV-DC-immunized hu-PBL-SCID mice and were re-stimulated in vitro by co-culture for 2 days with autologous adherent PBMC as antigen presenting cells, APC previously pulsed with inactivated HIV in IL-2-containing medium to expand HIV-1-reactive CD4(+) T cells. Aliquots of these re-stimulated CD4(+) T cells were then co-cultured with similar APC's that were previously pulsed with 10 microg/ml of a panel of HIV peptides for an additional 2 days, and their culture supernatants were examined for the production of both the R5 HIV-1 suppression factor and IFN-gamma. The data presented herein show that the HIV-1 primed CD4(+) T cells produced the R5 suppression factor in response to a wide variety of HIV-1 gag, env, pol, nef or vif peptides, depending on the donor of the CD4(+) T cells. Simultaneous production of human interferon (IFN)-gamma was observed in some cases. These results indicate that human CD4(+) T cells in PBMC of HIV-1 naive donors have a wide variety of HIV-1 epitope-specific CD4(+) T cell precursors that are capable of producing the R5 HIV-1 suppression factor upon DC-based vaccination with whole inactivated HIV-1.

  9. Combined effect of the environmental factors as ionizing radiation and a chronic iodine deficiency on the thyroid gland and the immune condition

    Energy Technology Data Exchange (ETDEWEB)

    Danyarova, L. [Department of Endocrynology, Research Institute of Cardiology and Internal Medicine, Almaty (Kazakhstan)

    2012-07-01

    The Semipalatinsk Test Site was the primary testing venue for the Soviet Union's nuclear weapons. It is located on the steppe in northeast Kazakhstan. The tragic situation of the Semipalatinsk region is an acute and chronic radiation, repeated in big and small doses and a total absence of territorial decontamination, created unique conditions for study of the long term influence of the radiation doses on the health of the population. The Semipalatinsk region of the Republic of Kazakhstan belongs also to an area of moderate and pronounced iodine deficiency. The purpose of the research is to study the prevalence of a thyroid gland pathology and the condition of a cytokine immune link that is likely to be influenced by a combine effect of ionizing radiation and a chronic iodine deficiency. 1100 people passed through the investigation and it appears that 56, 75% of them had a thyroid pathology. Thyroid gland functional condition analysis (TSH, FT3, FT4 a-TG, a-TPO) has shown the prevalence of a subclinical hypothyroidism (33%). 28, 8% resulted in the presence of antibodies to thyroglobulin and the thyroid peroxides, whereas in the areas located further to the nuclear range, the percentage was only 13, 0%

  10. Factors that Influence the Immunological Adjuvant Effect of Lactobacillus fermentum PC1 on Specific Immune Responses in Mice to Orally Administered Antigens

    Directory of Open Access Journals (Sweden)

    Meera Esvaran

    2016-07-01

    Full Text Available This study examined the influences of the dosage of the adjuvant, the nature of the antigen and the host genetics on the capacity of L. fermentum PC1 (PC1 to function as an oral adjuvant. BALB/c and DBA/1 mice were vaccinated with either ovalbumin (OVA or Salmonella Typhimurium on days 0 and 14, Mice were also dosed with the PC1 (108 CFU or 1011 CFU per dose per mouse with the antigens (days 0 and 14 and alone (days −1 and 13. The higher PC1 dose elicited a greater specific serum IgG2a response than IgG1 for both antigens and mice strains, indicating a Th1-biased humoral immune response. The Th1 bias was also observed at the cellular level with greater specific IFN-γ levels than IL-4 and IL-10 with both antigen types and mouse strains. With the particulate antigen, the lower dose of PC1 elicited a Th1 bias at the cellular level, but a balanced Th1/Th2 response at the systemic humoral level. With the soluble antigen, a strong Th1-biased response occurred at the cellular level while the systemic humoral response was Th2-biased. In conclusion, PC1 at the higher dose was an excellent Th1 adjuvant, which was unaffected by the nature of the antigen or the host’s genetic background.

  11. Comparison between Effects of Addition of Salvia mirzayanii Essence with Virginiamycin on Performance, Carcass Characteristics, Blood Factors and some Immune Parameters of Broiler Chickens

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    R. Mosaddegh

    2013-08-01

    Full Text Available In order to investigate effects of addition of Salvia mirzayanii essence and comparison with antibiotic an experiment was conducted as dietary a completely of the randomized design with 5 treatments, and 5 replicates with 12 chickens per replicate for 42 days with treatments control, virginiamycin antibiotic 10% (100 ppm and three levels of S. mirzayanii essence (200, 400 and 600 ppm. Weight gain and feed intake recorded weekly and carcass characteristics analysis and blood parameters were determined at 28 and 42 days of age. Highest weight gain was observed at the level of 200 ppm essence at the 22-42 days of age (grower phase and at1-42 days of age (total of experiment, 200 and 600 ppm essence showed the highest results. Feed intake was highest in 200 and 600ppm essence level in the grower phase as well as overall. Best feed conversion ratio at the grower phase and total of experiment observed in the 200 ppm essence treatment. Gizzard and gastrointestinal tract weights significantly decreased with addition of antibiotic. This essence significantly decreased cholesterol, HDL and LDL. Bursa of fabricius weight was significantly highest at level of 400 ppm essence and lowest at the level of 600 ppm. Dietary addition of essence significantly decreased blood eosinofil. The results of this experiment showed that S. mirzayanii essence could be used as growth promoter and using low levels of the essence could improve performance and immune system.

  12. Humoral immunity in Hansen's Disease

    Directory of Open Access Journals (Sweden)

    Waldenise Cossermelli-Messina

    Full Text Available For many years immune response in leprosy has been studied. Since 1960 several reports dealing with humoral immunity have been described in the literature. Different autoantibody rates occur in leprosy. There is an increase in the prevalence of autoantibodies in elderly patients with long standing disease, in lepromatous leprosy and in those with reactional states. The diferences in rates among various studies are attributed to different methods and variations among patient samples concerning age, gender, polar forms, therapy and other elements. The prevalence of numerous antibodies, immune complexes, cryoglobulins and complement levels have been studied by many authors. This also highlights the importance of the more recent reviews of anti-Mycobacterium leprae glycolipid antibodies such as the anti-phenolic glycolipid-I antibodies in which titers are variable and depend on genetic factors.

  13. Immune-modulating effects in mouse dendritic cells of lactobacilli and bifidobacteria isolated from individuals following omnivorous, vegetarian and vegan diets.

    Science.gov (United States)

    Luongo, Diomira; Treppiccione, Lucia; Sorrentino, Alida; Ferrocino, Ilario; Turroni, Silvia; Gatti, Monica; Di Cagno, Raffaella; Sanz, Yolanda; Rossi, Mauro

    2017-09-01

    Lactobacilli and bifidobacteria play a primary role in modulation of gut immunity. By considering that microbiota composition depends on various factors, including diet, we asked whether functional differences could characterize faecal populations of lactobacilli and bifidobacteria isolated from individuals with different dietary habits. 155 healthy volunteers who followed omnivorous, ovo-lacto-vegetarian or vegan diets were recruited at four Italian centres (Turin, Parma, Bologna and Bari). Faecal samples were collected; lactobacilli and bifidobacteria were isolated on selective media and their immunomodulatory activity was tested in mouse dendritic cells (DCs). Pre-incubation with lactobacilli increased LPS-induced expression of the maturation markers CD80 and CD86, whereas pre-incubation with bifidobacteria decreased such expression. Analysis of the cytokine profile indicated that strains of both genera induced down-regulation of IL-12 and up-regulation of IL-10, whereas expression of TNF-α was not modulated. Notably, analysis of anti-inflammatory potential (IL-10/IL-12 ratio) showed that lactobacilli evoked a greater anti-inflammatory effect than did bifidobacteria in the omnivorous group (P<0.05). We also found significantly reduced anti-inflammatory potential in the bacterial strains isolated from Bari's volunteers in comparison with those from the cognate groups from the other centres. In conclusion, lactobacilli and bifidobacteria showed a genus-specific ability of modulating in vitro innate immunity associated with a specific dietary habit. Furthermore, the geographical area had a significant impact on the anti-inflammatory potential of some components of faecal microbiota. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Sequential displacement of Type VI Secretion System effector genes leads to evolution of diverse immunity gene arrays in Vibrio cholerae

    Science.gov (United States)

    Kirchberger, Paul C.; Unterweger, Daniel; Provenzano, Daniele; Pukatzki, Stefan; Boucher, Yan

    2017-01-01

    Type VI secretion systems (T6SS) enable bacteria to engage neighboring cells in contact-dependent competition. In Vibrio cholerae, three chromosomal clusters each encode a pair of effector and immunity genes downstream of those encoding the T6SS structural machinery for effector delivery. Different combinations of effector-immunity proteins lead to competition between strains of V. cholerae, which are thought to be protected only from the toxicity of their own effectors. Screening of all publically available V. cholerae genomes showed that numerous strains possess long arrays of orphan immunity genes encoded in the 3′ region of their T6SS clusters. Phylogenetic analysis reveals that these genes are highly similar to those found in the effector-immunity pairs of other strains, indicating acquisition by horizontal gene transfer. Extensive genomic comparisons also suggest that successive addition of effector-immunity gene pairs replaces ancestral effectors, yet retains the cognate immunity genes. The retention of old immunity genes perhaps provides protection against nearby kin bacteria in which the old effector was not replaced. This mechanism, combined with frequent homologous recombination, is likely responsible for the high diversity of T6SS effector-immunity gene profiles observed for V. cholerae and closely related species. PMID:28327641

  15. Expression, Purification, and Functional Characterization of Atypical Xenocin, Its Immunity Protein, and Their Domains from Xenorhabdus nematophila

    Directory of Open Access Journals (Sweden)

    Jitendra Singh Rathore

    2013-01-01

    Full Text Available Xenorhabdus nematophila, a gram-negative bacterium belonging to the family Enterobacteriaceae is a natural symbiont of a soil nematode from the family Steinernematidae. In this study cloning, expression, and purification of broad range iron regulated multidomain bacteriocin called xenocin from X. nematophila (66 kDa, encoded by xcinA gene and its multidomain immunity protein (42 kDa, encoded by ximB gene have been done. xcinA-ximB (N′ terminal 270 bp, translocation, and translocation-receptor domain of xcinA, ximB, and its hemolysin domain were cloned, expressed, and purified by single step Ni-NTA chromatography under native conditions. In the functional characterization, neutralization of xcinA toxicity by immunity domain of ximB gene was determined by endogenous assay. Exogenous toxic assays results showed that only the purified recombinant xenocin-immunity domain (10 kDa protein complex had toxic activity. Atypical cognate immunity protein (42 kDa of xenocin was fusion of immunity domain (10 kDa and hemolysin domain (32 kDa. In silico analysis of immunity protein revealed its similarity with hemolysin and purine NTPase like proteins. Hemolytic activity was not observed in immunity protein or in its various domains; however, full-length immunity protein lacking Walker motif showed ATPase activity. Finally, using circular dichroism performed secondary structural analyses of all the recombinant proteins/protein complexes.

  16. Plasma-mediated immune suppression : a neonatal perspective

    NARCIS (Netherlands)

    Belderbos, Mirjam E.; Levy, Ofer; Meyaard, Linde; Bont, Louis

    Plasma is a rich mixture of immune regulatory factors that shape immune cell function. This immunomodulatory role of plasma is especially important in neonates. To maintain in utero feto-maternal tolerance and to allow for microbial colonization after birth, the neonatal immune system is biased

  17. Differential effect of immune cells on non-pathogenic Gram-negative bacteria-induced nuclear factor-kappaB activation and pro-inflammatory gene expression in intestinal epithelial cells

    DEFF Research Database (Denmark)

    Haller, D.; Holt, L.; Parlesak, Alexandr;

    2004-01-01

    We have previously shown that non-pathogenic Gram negative bacteria induce RelA phosphorylation, nuclear factor (NF)-kappaB transcriptional activity and pro-inflammatory gene expression in intestinal epithelial cells (IEC) in vivo and in vitro. In this study, we investigated the molecular mechanism...... of immune-epithelial cell cross-talk on Gram-negative enteric bacte