Distributions of Cognates in Europe as Based on Levenshtein Distance

Science.gov (United States)

Schepens, Job; Dijkstra, Ton; Grootjen, Franc

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 and non-cognates were identified across pairs of…

Cognate effects in sentence context depend on word class, L2 proficiency, and task

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Bultena, S.S.; Dijkstra, A.F.J.; Hell, J.G. van

2014-01-01

Noun translation equivalents that share orthographic and semantic features, called "cognates", are generally recognized faster than translation equivalents without such overlap. This cognate effect, which has also been obtained when cognates and noncognates were embedded in a sentence context,

English-Spanish Cognates in Picture Books: Toward a Vocabulary Curriculum for Latino ELLs

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Montelongo, José A.; Durán, Richard; Hernández, Anita C.

2013-01-01

English-Spanish cognates are words that are spelled similarly or identically and possess the same or nearly the same meanings in both languages. Many cognates are academic vocabulary words and are very common in content area textbooks. The primary purpose of this investigation was to obtain an estimate of the number of different cognates in…

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

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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.

Autoselection of cytoplasmic yeast virus like elements encoding toxin/antitoxin systems involves a nuclear barrier for immunity gene expression.

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Kast, Alene; Voges, Raphael; Schroth, Michael; Schaffrath, Raffael; Klassen, Roland; Meinhardt, Friedhelm

2015-05-01

Cytoplasmic virus like elements (VLEs) from Kluyveromyces lactis (Kl), Pichia acaciae (Pa) and Debaryomyces robertsiae (Dr) are extremely A/T-rich (>75%) and encode toxic anticodon nucleases (ACNases) along with specific immunity proteins. Here we show that nuclear, not cytoplasmic expression of either immunity gene (PaORF4, KlORF3 or DrORF5) results in transcript fragmentation and is insufficient to establish immunity to the cognate ACNase. Since rapid amplification of 3' ends (RACE) as well as linker ligation of immunity transcripts expressed in the nucleus revealed polyadenylation to occur along with fragmentation, ORF-internal poly(A) site cleavage due to the high A/T content is likely to prevent functional expression of the immunity genes. Consistently, lowering the A/T content of PaORF4 to 55% and KlORF3 to 46% by gene synthesis entirely prevented transcript cleavage and permitted functional nuclear expression leading to full immunity against the respective ACNase toxin. Consistent with a specific adaptation of the immunity proteins to the cognate ACNases, cross-immunity to non-cognate ACNases is neither conferred by PaOrf4 nor KlOrf3. Thus, the high A/T content of cytoplasmic VLEs minimizes the potential of functional nuclear recruitment of VLE encoded genes, in particular those involved in autoselection of the VLEs via a toxin/antitoxin principle.

Autoselection of cytoplasmic yeast virus like elements encoding toxin/antitoxin systems involves a nuclear barrier for immunity gene expression.

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Alene Kast

2015-05-01

Full Text Available Cytoplasmic virus like elements (VLEs from Kluyveromyces lactis (Kl, Pichia acaciae (Pa and Debaryomyces robertsiae (Dr are extremely A/T-rich (>75% and encode toxic anticodon nucleases (ACNases along with specific immunity proteins. Here we show that nuclear, not cytoplasmic expression of either immunity gene (PaORF4, KlORF3 or DrORF5 results in transcript fragmentation and is insufficient to establish immunity to the cognate ACNase. Since rapid amplification of 3' ends (RACE as well as linker ligation of immunity transcripts expressed in the nucleus revealed polyadenylation to occur along with fragmentation, ORF-internal poly(A site cleavage due to the high A/T content is likely to prevent functional expression of the immunity genes. Consistently, lowering the A/T content of PaORF4 to 55% and KlORF3 to 46% by gene synthesis entirely prevented transcript cleavage and permitted functional nuclear expression leading to full immunity against the respective ACNase toxin. Consistent with a specific adaptation of the immunity proteins to the cognate ACNases, cross-immunity to non-cognate ACNases is neither conferred by PaOrf4 nor KlOrf3. Thus, the high A/T content of cytoplasmic VLEs minimizes the potential of functional nuclear recruitment of VLE encoded genes, in particular those involved in autoselection of the VLEs via a toxin/antitoxin principle.

Activating KIR molecules and their cognate ligands prevail in children with a diagnosis of ASD and in their mothers.

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Guerini, Franca R; Bolognesi, Elisabetta; Chiappedi, Matteo; Manca, Salvatorica; Ghezzo, Alessandro; Agliardi, Cristina; Zanette, Michela; Littera, Roberto; Carcassi, Carlo; Sotgiu, Stefano; Clerici, Mario

2014-02-01

The activity of natural killer (NK) cells is modulated by the interaction between killer-cell immune globulin-like receptor (KIR) proteins and their cognate HLA ligands; activated NK cells produce inflammatory cytokines and mediate innate immune responses. Activating KIR/HLA complexes (aKIR/HLA) were recently suggested to prevail in children with autism spectrum disorders (ASD), a neurodevelopmental syndrome characterized by brain and behavioral abnormalities and associated with a degree of inflammation. We verified whether such findings could be confirmed by analyzing two sample cohorts of Sardinian and continental Italian ASD children and their mothers. Results showed that aKIR/HLA are increased whereas inhibitory KIR/HLA complexes are reduced in ASD children; notably this skewing was even more significant in their mothers. KIR and HLA molecules are expressed by placental cells and by the trophoblast and their interactions result in immune activation and influence fetal, as well as central nervous system development and plasticity. Data herein suggest that in utero KIR/HLA immune interactions favor immune activation in ASD; this may play a role in the pathogenesis of the disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Partial Diversity Generates Effector Immunity Specificity of the Bac41-Like Bacteriocins of Enterococcus faecalis Clinical Strains.

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Kurushima, Jun; Ike, Yasuyoshi; Tomita, Haruyoshi

2016-09-01

Bacteriocin 41 (Bac41) is the plasmid-encoded bacteriocin produced by the opportunistic pathogen Enterococcus faecalis Its genetic determinant consists of bacL1 (effector), bacL2 (regulator), bacA (effector), and bacI (immunity). The secreted effectors BacL1 and BacA coordinate to induce the lytic cell death of E. faecalis Meanwhile, the immunity factor BacI provides self-resistance to the Bac41 producer, E. faecalis, against the action of BacL1 and BacA. In this study, we demonstrated that more than half of the 327 clinical strains of E. faecalis screened had functional Bac41 genes. Analysis of the genetic structure of the Bac41 genes in the DNA sequences of the E. faecalis strains revealed that the Bac41-like genes consist of a relatively conserved region and a variable region located downstream from bacA Based on similarities in the variable region, the Bac41-like genes could be classified into type I, type IIa, and type IIb. Interestingly, the distinct Bac41 types had specific immunity factors for self-resistance, BacI1 or BacI2, and did not show cross-immunity to the other type of effector. We also demonstrated experimentally that the specificity of the immunity was determined by the combination of the C-terminal region of BacA and the presence of the unique BacI1 or BacI2 factor. These observations suggested that Bac41-like bacteriocin genes are extensively disseminated among E. faecalis strains in the clinical environment and can be grouped into at least three types. It was also indicated that the partial diversity results in specificity of self-resistance which may offer these strains a competitive advantage. Bacteriocins are antibacterial effectors produced by bacteria. In general, a bacteriocin-coding gene is accompanied by a cognate immunity gene that confers self-resistance on the bacteriocin-producing bacterium itself. We demonstrated that one of the bacteriocins, Bac41, is disseminated among E. faecalis clinical strains and the Bac41 subtypes with

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

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Mulder, Kimberley; Dijkstra, Ton; Baayen, R. Harald

2015-01-01

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 activation framework

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

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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

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

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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

A robust demonstration of the cognate facilitation effect in first-language and second-language naming.

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Sheng, Li; Lam, Boji Pak Wing; Cruz, Diana; Fulton, Aislynn

2016-01-01

The cognate facilitation effect refers to the phenomenon that in bilinguals performance on various vocabulary tasks is enhanced for cross-linguistic cognates as opposed to noncognates. However, research investigating the presence of the cognate advantage in bilingual children remains limited. Most studies with children conducted to date has not included a control group or rigorously designed stimuli, which may jeopardize the validity and robustness of the emerging evidence. The current study addressed these methodological problems by examining performance in picture naming tasks in 34 4- to 7-year-old Spanish-English bilinguals and 52 Mandarin-English bilinguals as well as 37 English-speaking monolinguals who served as controls. Stimuli were controlled for phonology, word frequency, and length. The Spanish-English bilinguals performed better for cognates than for noncognates and exhibited a greater number of doublet responses (i.e., providing correct responses in both languages) in naming cognate targets than in naming noncognates. The control groups did not show differences in performance between the two sets of words. These findings provide compelling evidence that cross-linguistic similarities at the phonological level allow bootstrapping of vocabulary learning. Copyright © 2015 Elsevier Inc. All rights reserved.

TAM Receptor Signaling in Immune Homeostasis

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

2015-01-01

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

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

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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…

Cognate xenoliths in Mt. Etna lavas: witnesses of the high-velocity body beneath the volcano

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Corsaro, Rosa Anna; Rotolo, Silvio Giuseppe; Cocina, Ornella; Tumbarello, Gianvito

2014-01-01

Various xenoliths have been found in lavas of the 1763 ("La Montagnola"), 2001, and 2002-03 eruptions at Mt. Etna whose petrographic evidence and mineral chemistry exclude a mantle origin and clearly point to a cognate nature. Consequently, cognate xenoliths might represent a proxy to infer the nature of the high-velocity body (HVB) imaged beneath the volcano by seismic tomography. Petrography allows us to group the cognate xenoliths as follows: i) gabbros with amphibole and amphibole-bearing mela-gabbros, ii) olivine-bearing leuco-gabbros, iii) leuco-gabbros with amphibole, and iv) Plg-rich leuco gabbros. Geobarometry estimates the crystallization pressure of the cognate xenoliths between 1.9 and 4.1 kbar. The bulk density of the cognate xenoliths varies from 2.6 to 3.0 g/cm3. P wave velocities (V P ), calculated in relation to xenolith density, range from 4.9 to 6.1 km/s. The integration of mineralogical, compositional, geobarometric data, and density-dependent V P with recent literature data on 3D V P seismic tomography enabled us to formulate the first hypothesis about the nature of the HVB which, in the depth range of 3-13 km b.s.l., is likely made of intrusive gabbroic rocks. These are believed to have formed at the "solidification front", a marginal zone that encompasses a deep region (>5 km b.s.l.) of Mt. Etna's plumbing system, within which magma crystallization takes place. The intrusive rocks were afterwards fragmented and transported as cognate xenoliths by the volatile-rich and fast-ascending magmas of the 1763 "La Montagnola", 2001 and 2002-03 eruptions.

Foreign language comprehension achievement: insights from the cognate facilitation effect

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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.

Molecular mechanism and function of CD40/CD40L engagement in the immune system.

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Elgueta, Raul; Benson, Micah J; de Vries, Victor C; Wasiuk, Anna; Guo, Yanxia; Noelle, Randolph J

2009-05-01

During the generation of a successful adaptive immune response, multiple molecular signals are required. A primary signal is the binding of cognate antigen to an antigen receptor expressed by T and B lymphocytes. Multiple secondary signals involve the engagement of costimulatory molecules expressed by T and B lymphocytes with their respective ligands. Because of its essential role in immunity, one of the best characterized of the costimulatory molecules is the receptor CD40. This receptor, a member of the tumor necrosis factor receptor family, is expressed by B cells, professional antigen-presenting cells, as well as non-immune cells and tumors. CD40 binds its ligand CD40L, which is transiently expressed on T cells and other non-immune cells under inflammatory conditions. A wide spectrum of molecular and cellular processes is regulated by CD40 engagement including the initiation and progression of cellular and humoral adaptive immunity. In this review, we describe the downstream signaling pathways initiated by CD40 and overview how CD40 engagement or antagonism modulates humoral and cellular immunity. Lastly, we discuss the role of CD40 as a target in harnessing anti-tumor immunity. This review underscores the essential role CD40 plays in adaptive immunity.

Purification, crystallization and preliminary X-ray analysis of OsAREB8 from rice, a member of the AREB/ABF family of bZIP transcription factors, in complex with its cognate DNA

International Nuclear Information System (INIS)

Miyazono, Ken-ichi; Koura, Tsubasa; Kubota, Keiko; Yoshida, Takuya; Fujita, Yasunari; Yamaguchi-Shinozaki, Kazuko; Tanokura, Masaru

2012-01-01

OsAREB8 from rice (O. sativa), a member of the AREB/ABF family of bZIP transcription factors, was expressed, purified and crystallized using the sitting-drop vapour-diffusion method. A crystal of OsAREB8 in complex with its cognate DNA diffracted X-rays to 3.65 Å resolution. The AREB/ABF family of bZIP transcription factors play a key role in drought stress response and tolerance during the vegetative stage in plants. To reveal the DNA-recognition mechanism of the AREB/ABF family of proteins, the bZIP domain of OsAREB8, an AREB/ABF-family protein from Oryza sativa, was expressed in Escherichia coli, purified and crystallized with its cognate DNA. Crystals of the OsAREB8–DNA complex were obtained by the sitting-drop vapour-diffusion method at 277 K with a reservoir solution consisting of 50 mM MES pH 6.4, 29% MPD, 2 mM spermidine, 20 mM magnesium acetate and 100 mM sodium chloride. A crystal diffracted X-rays to 3.65 Å resolution and belonged to space group C222, with unit-cell parameters a = 155.1, b = 206.7, c = 38.5 Å. The crystal contained one OsAREB8–DNA complex in the asymmetric unit

Transgenerational Social Stress, Immune Factors, Hormones, and Social Behavior

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Christopher Anthony Murgatroyd

2016-01-01

Full Text Available A social signal transduction theory of depression has been proposed that states that exposure to social adversity alters the immune response and these changes mediate symptoms of depression such as anhedonia and impairments in social behavior. The exposure of maternal rats to the chronic social stress (CSS of a male intruder depresses maternal care and impairs social behavior in the F1 and F2 offspring of these dams. The objective of the present study was to characterize basal peripheral levels of several immune factors and related hormone levels in the adult F2 offspring of CSS exposed dams and assess whether changes in these factors are associated with previously reported deficits in allogrooming behavior. CSS decreased acid glycoprotein (α1AGP and intercellular adhesion molecule-1 (ICAM-1 in F2 females, and increased granulocyte macrophage-colony stimulating factor (GM-CSF in F2 males. There were also sex dependent changes in IL-18, tissue inhibitors of metalloproteinases 1 (TIMP-1, and vascular endothelial growth factor (VEGF. Progesterone was decreased and alpha melanocyte stimulating hormone (α-MSH was increased in F2 males, and brain-derived neurotrophic factor (BDNF was decreased in F2 females. Changes in α1AGP, GM-CSF, progesterone and α-MSH were correlated with decreased allogrooming in the F2 offspring of stressed dams. These results support the hypothesis that transgenerational social stress affects both the immune system and social behavior, and also support previous studies on the adverse effects of early life stress on immune functioning and stress associated immunological disorders, including the increasing prevalence of asthma. The immune system may represent an important transgenerational etiological factor in disorders which involve social and/or early life stress associated changes in social behavior, such as depression, anxiety, and autism, as well as comorbid immune disorders. Future studies involving immune and

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.

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

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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…

Distinction of the memory B cell response to cognate antigen versus bystander inflammatory signals.

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Benson, Micah J; Elgueta, Raul; Schpero, William; Molloy, Michael; Zhang, Weijun; Usherwood, Edward; Noelle, Randolph J

2009-08-31

The hypothesis that bystander inflammatory signals promote memory B cell (B(MEM)) self-renewal and differentiation in an antigen-independent manner is critically evaluated herein. To comprehensively address this hypothesis, a detailed analysis is presented examining the response profiles of B-2 lineage B220(+)IgG(+) B(MEM) toward cognate protein antigen in comparison to bystander inflammatory signals. After in vivo antigen encounter, quiescent B(MEM) clonally expand. Surprisingly, proliferating B(MEM) do not acquire germinal center (GC) B cell markers before generating daughter B(MEM) and differentiating into plasma cells or form structurally identifiable GCs. In striking contrast to cognate antigen, inflammatory stimuli, including Toll-like receptor agonists or bystander T cell activation, fail to induce even low levels of B(MEM) proliferation or differentiation in vivo. Under the extreme conditions of adjuvanted protein vaccination or acute viral infection, no detectable bystander proliferation or differentiation of B(MEM) occurred. The absence of a B(MEM) response to nonspecific inflammatory signals clearly shows that B(MEM) proliferation and differentiation is a process tightly controlled by the availability of cognate antigen.

Immunity to intestinal pathogens: lessons learned from Salmonella

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McSorley, Stephen J.

2014-01-01

Summary Salmonella are a common source of food or water-borne infection and cause a wide range of clinical disease in human and animal hosts. Salmonella are relatively easy to culture and manipulate in a laboratory setting, and the infection of laboratory animals induces robust innate and adaptive immune responses. Thus, immunologists have frequently turned to Salmonella infection models to expand understanding of immunity to intestinal pathogens. In this review, I summarize current knowledge of innate and adaptive immunity to Salmonella and highlight features of this response that have emerged from recent studies. These include the heterogeneity of the antigen-specific T-cell response to intestinal infection, the prominence of microbial mechanisms to impede T and B-cell responses, and the contribution of non-cognate pathways for elicitation of T-cell effector functions. Together, these different issues challenge an overly simplistic view of host-pathogen interaction during mucosal infection but also allow deeper insight into the real-world dynamic of protective immunity to intestinal pathogens. PMID:24942689

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

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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…

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, Andrezj; Goulding, Celia W.

2015-05-20

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 fromNeisseria meningitidisMC58 is presented at 1.45 Å 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 fromXenopus 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.

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

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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. ©2011 The British Psychological Society.

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

African Journals Online (AJOL)

Risk factors for discordant immune response among HIV-infected patients initiating antiretroviral therapy: A retrospective cohort study. ... Multivariate logistic regression models were used to estimate adjusted odds ratios (AORs) to determine associations between discordant immune response and clinical and demographic ...

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

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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.

ANALYSIS OF FACTORS CAUSE LOW INFANT IMMUNIZATION ACHIEVEMENTS IN TANJUNGSARI CLINICSANALYSIS OF FACTORS CAUSE LOW INFANT IMMUNIZATION ACHIEVEMENTS IN PUBLIC HEALTH DISTRIC

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Juni Kurnia Santi

2016-07-01

Full Text Available Immunization is a promotif and preventive efforts in basic health services play an important role in the decline of infant mortality that occurs due to a disease that can be prevented by immunization (PD3I. Annual reports from public health Tanjungsari noted that the results of the coverage of immunization activities results of the baby has not yet reached the target UCI (Uneversal Child Immunization. An assumption of the reason for immunization low coverage was the way on how Public Heath Center implemented its management funtion : planning, actuacting (supervision, coordination, cold chain, work load, motivation, evaluating and the result of baby`s immunization program. The risset of study is observational study. tanjunsari Public Health Center district the unit of analysis of this study. The object of study was all immunization program documentation which constituted of planning, implementation, supervision check list, coordination check list, evaluation documents as well as the document of coverage results. The respondent were the personnel of immunization program. The results of study revealed baby`s immunization until four years old is 86% campak, 89% DPT1, 86% DPT3, 87% Polio4, 84% BCG dan 85% HB3. Conclusively, it can derived that was discovered that the coverage of baby`s immunization was far below the UCI (Universal Child Immunization standart in public health, implementatiton (supervision, coordination, clod chain, load work, motivation and evaluating immunization program has nor been performed well. The inhibiting factors are now knowledge the process Planning Of Action formulation, no supervision to immunization program dan insufficient motivation to personnel immunization program. Key words : planning, immunization program, Public Health

Innate immune factors associated with HIV-1 transmission

NARCIS (Netherlands)

Pollakis, Georgios; Stax, Martijn J.; Paxton, William A.

2011-01-01

Relatively little is known with regards to the mechanisms of HIV-1 transmission across a mucosal surface and more specifically what effects host factors have on influencing infection and early viral dissemination. The purpose of this review is to summarize which factors of the innate immune response

Complement anaphylatoxins as immune regulators in cancer.

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Sayegh, Eli T; Bloch, Orin; Parsa, Andrew T

2014-08-01

The role of the complement system in innate immunity is well characterized. However, a recent body of research implicates the complement anaphylatoxins C3a and C5a as insidious propagators of tumor growth and progression. It is now recognized that certain tumors elaborate C3a and C5a and that complement, as a mediator of chronic inflammation and regulator of immune function, may in fact foster rather than defend against tumor growth. A putative mechanism for this function is complement-mediated suppression of immune effector cells responsible for immunosurveillance within the tumor microenvironment. This paradigm accords with models of immune dysregulation, such as autoimmunity and infectious disease, which have defined a pathophysiological role for abnormal complement signaling. Several types of immune cells express the cognate receptors for the complement anaphylatoxins, C3aR and C5aR, and demonstrate functional modulation in response to complement stimulation. In turn, impairment of antitumor immunity has been intimately tied to tumor progression in animal models of cancer. In this article, the literature was systematically reviewed to identify studies that have characterized the effects of the complement anaphylatoxins on the composition and function of immune cells within the tumor microenvironment. The search identified six studies based upon models of lymphoma and ovarian, cervical, lung, breast, and mammary cancer, which collectively support the paradigm of complement as an immune regulator in the tumor microenvironment. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Identification of the cognate peptide-MHC target of T cell receptors using molecular modeling and force field scoring

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Lanzarotti, Esteban; Marcatili, Paolo; Nielsen, Morten

2018-01-01

Interactions of T cell receptors (TCR) to peptides in complex with MHC (p:MHC) are key features that mediate cellular immune responses. While MHC binding is required for a peptide to be presented to T cells, not all MHC binders are immunogenic. The interaction of a TCR to the p:MHC complex holds...... terms. Building a benchmark of TCR:p:MHC complexes where epitopes and non-epitopes are modelled using state-of-the-art molecular modelling tools, scoring p:MHC to a given TCR using force-fields, optimized in a cross-validation setup to evaluate TCR inter atomic interactions involved with each p:MHC, we...... and model the TCR:p:MHC complex structure. In summary, we conclude that it is possible to identify the TCR cognate target among different candidate peptides by using a force-field based model, and believe this works could lay the foundation for future work within prediction of TCR:p:MHC interactions....

Cross-Linguistic Influence in the Bilingual Mental Lexicon: Evidence of Cognate Effects in the Phonetic Production and Processing of a Vowel Contrast.

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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.

A Killer Immunoglobulin - Like Receptor Gene - Content Haplotype and A Cognate Human Leukocyte Antigen Ligand are Associated with Autism

OpenAIRE

Torres, Anthony; Westover, Jonna; Benson, Michael; Johnson, Randall; Dykes, Annelise

2016-01-01

The killing activity of natural killer cells is largely regulated by the binding of class I human leukocyte antigen cognate ligands to killer cell immunoglobulin - like receptor proteins. The killer cell immunoglobulin - like receptor gene - complex contains genes that activate and others that inhibit the killing state of natural killer cells depending on the binding of specific human leukocyte antigen cognate ligands. It has been suggested in previous publications that activating human leuko...

The use of CD47-modified biomaterials to mitigate the immune response.

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Tengood, Jillian E; Levy, Robert J; Stachelek, Stanley J

2016-05-01

Addressing the aberrant interactions between immune cells and biomaterials represents an unmet need in biomaterial research. Although progress has been made in the development of bioinert coatings, identifying and targeting relevant cellular and molecular pathways can provide additional therapeutic strategies to address this major healthcare concern. To that end, we describe the immune inhibitory motif, receptor-ligand pairing of signal regulatory protein alpha and its cognate ligand CD47 as a potential signaling pathway to enhance biocompatibility. The goals of this article are to detail the known roles of CD47-signal regulatory protein alpha signal transduction pathway and to describe how immobilized CD47 can be used to mitigate the immune response to biomaterials. Current applications of CD47-modified biomaterials will also be discussed herein. © 2016 by the Society for Experimental Biology and Medicine.

Immunization, urbanization and slums - a systematic review of factors and interventions.

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Crocker-Buque, Tim; Mindra, Godwin; Duncan, Richard; Mounier-Jack, Sandra

2017-06-08

In 2014, over half (54%) of the world's population lived in urban areas and this proportion will increase to 66% by 2050. This urbanizing trend has been accompanied by an increasing number of people living in urban poor communities and slums. Lower immunization coverage is found in poorer urban dwellers in many contexts. This study aims to identify factors associated with immunization coverage in poor urban areas and slums, and to identify interventions to improve coverage. We conducted a systematic review, searching Medline, Embase, Global Health, CINAHL, Web of Science and The Cochrane Database with broad search terms for studies published between 2000 and 2016. Of 4872 unique articles, 327 abstracts were screened, leading to 63 included studies: 44 considering factors and 20 evaluating interventions (one in both categories) in 16 low or middle-income countries. A wide range of socio-economic characteristics were associated with coverage in different contexts. Recent rural-urban migration had a universally negative effect. Parents commonly reported lack of awareness of immunization importance and difficulty accessing services as reasons for under-immunization of their children. Physical distance to clinics and aspects of service quality also impacted uptake. We found evidence of effectiveness for interventions involving multiple components, especially if they have been designed with community involvement. Outreach programmes were effective where physical distance was identified as a barrier. Some evidence was found for the effective use of SMS (text) messaging services, community-based education programmes and financial incentives, which warrant further evaluation. No interventions were identified that provided services to migrants from rural areas. Different factors affect immunization coverage in different urban poor and slum contexts. Immunization services should be designed in collaboration with slum-dwelling communities, considering the local context

Immune responses to influenza virus and its correlation to age and inherited factors

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Azadeh Bahadoran

2016-11-01

Full Text Available Influenza viruses belong to the family Orthomyxoviridae of enveloped viruses and are an important cause of respiratory infections worldwide. The influenza virus is able to infect a wide variety species as diverse as poultry, marine, pigs, horses and humans. Upon infection with influenza virus the innate immunity plays a critical role in efficient and rapid control of viral infections as well as in adaptive immunity initiation. The humoral immune system produces antibodies against different influenza antigens, of which the HA-specific antibody is the most important for neutralization of the virus and thus prevention of illness. Cell mediated immunity including CD4+ helper T cells and CD8+ cytotoxic T cells are the other arms of adaptive immunity induced upon influenza virus infection. The complex inherited factors and age related changes are associated with the host immune responses. Here, we review the different components of immune responses against influenza virus. Additionally, the correlation of the immune response to age and inherited factors has been discussed. These determinations lead to a better understanding of the limitations of immune responses for developing improved vaccines to control influenza virus infection.

COGNAT: a web server for comparative analysis of genomic neighborhoods.

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Klimchuk, Olesya I; Konovalov, Kirill A; Perekhvatov, Vadim V; Skulachev, Konstantin V; Dibrova, Daria V; Mulkidjanian, Armen Y

2017-11-22

In prokaryotic genomes, functionally coupled genes can be organized in conserved gene clusters enabling their coordinated regulation. Such clusters could contain one or several operons, which are groups of co-transcribed genes. Those genes that evolved from a common ancestral gene by speciation (i.e. orthologs) are expected to have similar genomic neighborhoods in different organisms, whereas those copies of the gene that are responsible for dissimilar functions (i.e. paralogs) could be found in dissimilar genomic contexts. Comparative analysis of genomic neighborhoods facilitates the prediction of co-regulated genes and helps to discern different functions in large protein families. We intended, building on the attribution of gene sequences to the clusters of orthologous groups of proteins (COGs), to provide a method for visualization and comparative analysis of genomic neighborhoods of evolutionary related genes, as well as a respective web server. Here we introduce the COmparative Gene Neighborhoods Analysis Tool (COGNAT), a web server for comparative analysis of genomic neighborhoods. The tool is based on the COG database, as well as the Pfam protein families database. As an example, we show the utility of COGNAT in identifying a new type of membrane protein complex that is formed by paralog(s) of one of the membrane subunits of the NADH:quinone oxidoreductase of type 1 (COG1009) and a cytoplasmic protein of unknown function (COG3002). This article was reviewed by Drs. Igor Zhulin, Uri Gophna and Igor Rogozin.

Immune Defence Factors In Human Milk

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Kumar Sanjeev

1985-01-01

Full Text Available Scientific evidence is accumulating to prove the nutritional, anti-infective, anti-fertility, psychosomal and economic advantages of breast-feeding. A number of studies have shown that breast milk protects against diarrheal, respiratory and other infections. Its value in protecting against allergy has also been established. This article reviews the studies on various immune defence factors present in the human milk. The available scientific knowledge makes a very strong case in favour of promoting breast-feeding.

Subtle variation within conserved effector operon gene products contributes to T6SS-mediated killing and immunity.

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Alteri, Christopher J; Himpsl, Stephanie D; Zhu, Kevin; Hershey, Haley L; Musili, Ninette; Miller, Jessa E; Mobley, Harry L T

2017-11-01

Type VI secretion systems (T6SS) function to deliver lethal payloads into target cells. Many studies have shown that protection against a single, lethal T6SS effector protein requires a cognate antidote immunity protein, both of which are often encoded together in a two-gene operon. The T6SS and an effector-immunity pair is sufficient for both killing and immunity. HereIn this paper we describe a T6SS effector operon that differs from conventional effector-immunity pairs in that eight genes are necessary for lethal effector function, yet can be countered by a single immunity protein. In this study, we investigated the role that the PefE T6SS immunity protein plays in recognition between two strains harboring nearly identical effector operons. Interestingly, despite containing seven of eight identical effector proteins, the less conserved immunity proteins only provided protection against their native effectors, suggesting that specificity and recognition could be dependent on variation within an immunity protein and one effector gene product. The variable effector gene product, PefD, is encoded upstream from pefE, and displays toxic activity that can be countered by PefE independent of T6SS-activity. Interestingly, while the entire pef operon was necessary to exert toxic activity via the T6SS in P. mirabilis, production of PefD and PefE alone was unable to exert this effector activity. Chimeric PefE proteins constructed from two P. mirabilis strains were used to localize immunity function to three amino acids. A promiscuous immunity protein was created using site-directed mutagenesis to change these residues from one variant to another. These findings support the notion that subtle differences between conserved effectors are sufficient for T6SS-mediated kin discrimination and that PefD requires additional factors to function as a T6SS-dependent effector.

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

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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…

Differential Effects of Environmental and Genetic Factors on T and B Cell Immune Traits

NARCIS (Netherlands)

Aguirre-Gamboa, Raul; Joosten, Irma; Urbano, Paulo C. M.; van der Molen, Renate G.; van Rijssen, Esther; van Cranenbroek, Bram; Oosting, Marije; Smeekens, Sanne; Jaeger, Martin; Zorro, Maria; Withoff, Sebo; van Herwaarden, Antonius E.; Sweep, Fred C. G. J.; Netea, Romana T.; Swertz, Morris A.; Franke, Lude; Xavier, Ramnik J.; Joosten, Leo A. B.; Netea, Mihai G.; Wijmenga, Cisca; Kumar, Vinod; Li, Yang; Koenen, Hans J. P. M.

2016-01-01

Effective immunity requires a complex network of cellular and humoral components that interact with each other and are influenced by different environmental and host factors. We used a systems biology approach to comprehensively assess the impact of environmental and genetic factors on immune cell

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

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

2013-01-01

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

Immune Checkpoint Inhibitor-Associated Type 1 Diabetes Mellitus: Case Series, Review of the Literature, and Optimal Management

OpenAIRE

Kapke, Jonathan; Shaheen, Zachary; Kilari, Deepak; Knudson, Paul; Wong, Stuart

2017-01-01

With the introduction of immune checkpoint inhibitors into clinical practice, various autoimmune toxicities have been described. Antibodies targeting the receptor:ligand pairing of programmed death receptor-1 (PD-1) and its cognate ligand programmed death-ligand 1 (PD-L1) in rare reports have been associated with autoimmune diabetes mellitus. We report 2 cases of rapid-onset, insulin-dependent, type 1 diabetes mellitus in the setting of administration of nivolumab, a fully human monoclonal an...

Distinct colicin M-like bacteriocin-immunity pairs in Burkholderia.

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Ghequire, Maarten G K; De Mot, René

2015-11-27

The Escherichia coli bacteriocin colicin M (ColM) acts via degradation of the cell wall precursor lipid II in target cells. ColM producers avoid self-inhibition by a periplasmic immunity protein anchored in the inner membrane. In this study, we identified colM-like bacteriocin genes in genomes of several β-proteobacterial strains belonging to the Burkholderia cepacia complex (Bcc) and the Burkholderia pseudomallei group. Two selected Burkholderia ambifaria proteins, designated burkhocins M1 and M2, were produced recombinantly and showed antagonistic activity against Bcc strains. In their considerably sequence-diverged catalytic domain, a conserved aspartate residue equally proved pivotal for cytotoxicity. Immunity to M-type burkhocins is conferred upon susceptible strains by heterologous expression of a cognate gene located either upstream or downstream of the toxin gene. These genes lack homology with currently known ColM immunity genes and encode inner membrane-associated proteins of two distinct types, differing in predicted transmembrane topology and moiety exposed to the periplasm. The addition of burkhocins to the bacteriocin complement of Burkholderia reveals a wider phylogenetic distribution of ColM-like bacteriotoxins, beyond the γ-proteobacterial genera Escherichia, Pectobacterium and Pseudomonas, and illuminates the diversified nature of immunity-providing proteins.

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

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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.

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

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L.I. Chernyshova

2013-10-01

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.

Natural immunity factors in Polish mixed breed rabbits.

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Tokarz-Deptuła, B; Niedźwiedzka-Rystwej, P; Adamiak, M; Hukowska-Szematowicz, B; Trzeciak-Ryczek, A; Deptuła, W

2015-01-01

Mixed-breed rabbits in Poland are widely used for diagnostic and scientific research and as utility animals, therefore there is a need to know their immunological status, as well as their haematological status. In this study natural immunity factors were analyzed in Polish mixed-breed rabbits and Polish mixed-breed rabbits with addition of blood of meet-breed, considering the impact of sex and season of the year (spring, summer, autumn, winter) using measurement of non-specific cellular and humoral immunity parameters in peripheral blood. The study has revealed that there is a variety between the two commonly used mixed-breed types of rabbits, especially when sex and season is concerned, which is crucial for using these animals in experiments.

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

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Hua-Jia Dai

2016-05-01

Full Text Available 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.

Factors Affecting the Immunity to Respiratory Syncytial Virus: From Epigenetics to Microbiome

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Wendy Fonseca

2018-02-01

Full Text Available Respiratory syncytial virus (RSV is a common pathogen that infects virtually all children by 2 years of age and is the leading cause of hospitalization of infants worldwide. While most children experience mild symptoms, some children progress to severe lower respiratory tract infection. Those children with severe disease have a much higher risk of developing childhood wheezing later in life. Many risk factors are known to result in exacerbated disease, including premature birth and early age of RSV infection, when the immune system is relatively immature. The development of the immune system before and after birth may be altered by several extrinsic and intrinsic factors that could lead to severe disease predisposition in children who do not exhibit any currently known risk factors. Recently, the role of the microbiome and the resulting metabolite profile has been an area of intense study in the development of lung disease, including viral infection and asthma. This review explores both known risk factors that can lead to severe RSV-induced disease as well as emerging topics in the development of immunity to RSV and the long-term consequences of severe infection.

Activating Transcription Factor 3 Regulates Immune and Metabolic Homeostasis

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Rynes, Jan; Donohoe, Colin D.; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek

2012-01-01

Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins. PMID:22851689

Activating transcription factor 3 regulates immune and metabolic homeostasis.

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Rynes, Jan; Donohoe, Colin D; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek; Uhlirova, Mirka

2012-10-01

Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins.

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

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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.

Incomplete childhood immunization in Nigeria: a multilevel analysis of individual and contextual factors

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Sulaimon T. Adedokun

2017-03-01

Full Text Available Abstract Background Under-five mortality remains high in sub-Saharan Africa despite global decline. One quarter of these deaths are preventable through interventions such as immunization. The aim of this study was to examine the independent effects of individual-, community- and state-level factors on incomplete childhood immunization in Nigeria, which is one of the 10 countries where most of the incompletely immunised children in the world live. Methods The study was based on secondary analyses of cross-sectional data from the 2013 Nigeria Demographic and Health Survey (DHS. Multilevel multivariable logistic regression models were applied to the data on 5,754 children aged 12–23 months who were fully immunized or not (level 1, nested within 896 communities (level 2 from 37 states (level 3. Results More than three-quarter of the children (76.3% were not completely immunized. About 83% of children of young mothers (15–24 years and 94% of those whose mothers are illiterate did not receive full immunization. In the fully adjusted model, the chances of not being fully immunized reduced for children whose mothers attended antenatal clinic (adjusted odds ratio [aOR] = 0.49; 95% credible interval [CrI] = 0.39–0.60, delivered in health facility (aOR = 0.62; 95% CrI = 0.51–0.74 and lived in urban area (aOR = 0.66; 95% CrI = 0.50–0.82. Children whose mothers had difficulty getting to health facility (aOR = 1.28; 95% CrI = 1.02–1.57 and lived in socioeconomically disadvantaged communities (aOR = 2.93; 95% CrI = 1.60–4.71 and states (aOR = 2.69; 955 CrI =1.37–4.73 were more likely to be incompletely immunized. Conclusions This study has revealed that the risk of children being incompletely immunized in Nigeria was influenced by not only individual factors but also community- and state-level factors. Interventions to improve child immunization uptake should take into consideration these contextual

Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity.

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Hamilton, Gerhard; Rath, Barbara

2017-04-01

Immune checkpoint inhibition holds great promise for selected tumors. The human monoclonal antibody (mAB) avelumab is directed to programmed death ligand-1 (PD-L1) and is supposed to inhibit the immunosuppressive PD-L1/PD-1 interaction and, furthermore, effect antibody-dependent cytotoxicity (ADCC) lysis of tumor cells. Areas covered: This article presents an overview of the current means to activate the antitumor immune defense by targeting PD-1 or PD-L1 with mABs and their possible role in ADCC-mediated tumor cell elimination. Expert opinion: Avelumab contains a Fc region which can bind cognate receptors on immune effector cells and induce ADCC-mediated tumor cell lysis, in contrast to other mABs directed to PD-1/PD-L1 which lack the ability to trigger ADCC due to belonging to the IgG4 subclass or possessing a mutated Fc region. Preclinical and clinical data indicate that avelumab can be safely administered to cancer patients with a toxicity profile comparable to other mABs and without lysis of PD-L1-positive activated immune cells. This antibody yielded durable responses in a phase II trial in advanced Merkel cell carcinoma patients. Tumor cell lysis by avelumab prevents cells from resorting to alternative checkpoints as shown by targeting PD-1 and the upregulation of TIM-3.

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

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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.

Innate and adaptive immune traits are differentially affected by genetic and environmental factors

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Mangino, Massimo; Roederer, Mario; Beddall, Margaret H.; Nestle, Frank O.; Spector, Tim D.

2017-01-01

The diversity and activity of leukocytes is controlled by genetic and environmental influences to maintain balanced immune responses. However, the relative contribution of environmental compared with genetic factors that affect variations in immune traits is unknown. Here we analyse 23,394 immune phenotypes in 497 adult female twins. 76% of these traits show a predominantly heritable influence, whereas 24% are mostly influenced by environment. These data highlight the importance of shared childhood environmental influences such as diet, infections or microbes in shaping immune homeostasis for monocytes, B1 cells, γδ T cells and NKT cells, whereas dendritic cells, B2 cells, CD4+ T and CD8+ T cells are more influenced by genetics. Although leukocyte subsets are influenced by genetics and environment, adaptive immune traits are more affected by genetics, whereas innate immune traits are more affected by environment. PMID:28054551

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

The role of granulocyte macrophage-colony stimulating factor in gastrointestinal immunity to salmonellosis.

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Coon, C; Beagley, K W; Bao, S

2009-08-01

Human Salmonella infection, in particular, typhoid fever is a highly infectious disease that remains a major public health problem causing significant morbidity and mortality. The outcome of these infections depends on the host's immune response, particularly the actions of granulocytes and macrophages. Using a mouse model of human typhoid fever, with Salmonella typhimurium infection of wild type and granulocyte macrophage-colony stimulating factor (GM-CSF) knock out mice we show a delay in the onset of immune-mediated tissue damage in the spleens and livers of GM-CSF(-/-) mice. Furthermore, GM-CSF(-/-) mice have a prolonged sequestration of S. typhimurium in affected tissues despite an increased production of F4/80+ effector cells. Moreover in the absence of GM-CSF, a decrease in pro-inflammatory cytokine expression of tumor necrosis factor-alpha, interleukin-12 (IL-12) and IL-18 was found, which may alter the host's immune response to infection. GM-CSF appears to play an important role in the pathogenesis of Salmonellosis, and may contribute significantly to the development of protective gastrointestinal mucosal immune responses against oral pathogens.

The Specificity of Innate Immune Responses Is Enforced by Repression of Interferon Response Elements by NF-κB p50

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Cheng, Christine S.; Feldman, Kristyn E.; Lee, James; Verma, Shilpi; Huang, De-Bin; Huynh, Kim; Chang, Mikyoung; Ponomarenko, Julia V.; Sun, Shao-Cong; Benedict, Chris A.; Ghosh, Gourisankar; Hoffmann, Alexander

2011-01-01

The specific binding of transcription factors to cognate sequence elements is thought to be critical for the generation of specific gene expression programs. Members of the nuclear factor κB (NF-κB) and interferon (IFN) regulatory factor (IRF) transcription factor families bind to the κB site and the IFN response element (IRE), respectively, of target genes, and they are activated in macrophages after exposure to pathogens. However, how these factors produce pathogen-specific inflammatory and immune responses remains poorly understood. Combining top-down and bottom-up systems biology approaches, we have identified the NF-κB p50 homodimer as a regulator of IRF responses. Unbiased genome-wide expression and biochemical and structural analyses revealed that the p50 homodimer repressed a subset of IFN-inducible genes through a previously uncharacterized subclass of guanine-rich IRE (G-IRE) sequences. Mathematical modeling predicted that the p50 homodimer might enforce the stimulus specificity of composite promoters. Indeed, the production of the antiviral regulator IFN-β was rendered stimulus-specific by the binding of the p50 homodimer to the G-IRE–containing IFNβ enhancer to suppress cytotoxic IFN signaling. Specifically, a deficiency in p50 resulted in the inappropriate production of IFN-β in response to bacterial DNA sensed by Toll-like receptor 9. This role for the NF-κB p50 homodimer in enforcing the specificity of the cellular response to pathogens by binding to a subset of IRE sequences alters our understanding of how the NF-κB and IRF signaling systems cooperate to regulate antimicrobial immunity. PMID:21343618

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.

Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity.

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Lorenzo Asti

2016-04-01

Full Text Available The immune system has developed a number of distinct complex mechanisms to shape and control the antibody repertoire. One of these mechanisms, the affinity maturation process, works in an evolutionary-like fashion: after binding to a foreign molecule, the antibody-producing B-cells exhibit a high-frequency mutation rate in the genome region that codes for the antibody active site. Eventually, cells that produce antibodies with higher affinity for their cognate antigen are selected and clonally expanded. Here, we propose a new statistical approach based on maximum entropy modeling in which a scoring function related to the binding affinity of antibodies against a specific antigen is inferred from a sample of sequences of the immune repertoire of an individual. We use our inference strategy to infer a statistical model on a data set obtained by sequencing a fairly large portion of the immune repertoire of an HIV-1 infected patient. The Pearson correlation coefficient between our scoring function and the IC50 neutralization titer measured on 30 different antibodies of known sequence is as high as 0.77 (p-value 10-6, outperforming other sequence- and structure-based models.

The Role of TAM Family Receptors in Immune Cell Function: Implications for Cancer Therapy.

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Paolino, Magdalena; Penninger, Josef M

2016-10-21

The TAM receptor protein tyrosine kinases-Tyro3, Axl, and Mer-are essential regulators of immune homeostasis. Guided by their cognate ligands Growth arrest-specific gene 6 (Gas6) and Protein S (Pros1), these receptors ensure the resolution of inflammation by dampening the activation of innate cells as well as by restoring tissue function through promotion of tissue repair and clearance of apoptotic cells. Their central role as negative immune regulators is highlighted by the fact that deregulation of TAM signaling has been linked to the pathogenesis of autoimmune, inflammatory, and infectious diseases. Importantly, TAM receptors have also been associated with cancer development and progression. In a cancer setting, TAM receptors have a dual regulatory role, controlling the initiation and progression of tumor development and, at the same time, the associated anti-tumor responses of diverse immune cells. Thus, modulation of TAM receptors has emerged as a potential novel strategy for cancer treatment. In this review, we discuss our current understanding of how TAM receptors control immunity, with a particular focus on the regulation of anti-tumor responses and its implications for cancer immunotherapy.

Plasma levels of immune factors and sex steroids in the male seahorse Hippocampus erectus during a breeding cycle.

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Lin, Tingting; Liu, Xin; Xiao, Dongxue; Zhang, Dong

2017-06-01

To better understand the endocrine- and immune-response pattern during reproduction in a fish species having parental care behaviors and also to accumulate the endocrine- and immune-related data for future explanations of the low reproductive efficiency in seahorse species, the variations of immune factors and sex steroids in the plasma of the male lined seahorse Hippocampus erectus at different breeding stages, i.e., pre-pregnancy, pregnancy (early, middle, and late periods), and post-pregnancy, were investigated in the present study. The immune factors included monocytes/leucocytes (M/L), leucocyte phagocytic rate (LPR), immunoglobulin M (Ig M), interleukin-2 (IL-2), interferon-α (IFN-α), and lysozyme (LZM). The sex steroids included testosterone (T), 11-ketotestosterone (11-KT), 11β-hydroxytestosterone (11β-OHT), 17α-methyltestosterone (17α-MT), 17β-estradiol (E2), and 17α-hydroxy-20β-dihydroprogesterone (17α-20β-P). Moreover, the immune metabolic activity of epithelium cells in the brood pouch at different breeding stages was also analyzed through ultrastructural observations of the abundance of cytoplasmic granules, mitochondria, endoplasmic reticulum, lysosomes, and exocytosis. The results show that a higher immune level was observed during pregnancy, particularly in the early and middle periods, and a lower immune level was noted during pre-pregnancy. Correspondingly, the epithelium cells in the brood pouch also showed a stronger immune metabolic activity during pregnancy and weaker activity during pre-pregnancy. Four sex steroids of T, 11β-OHT, 17α-MT, and E2 were higher during pre-pregnancy and lower during post-pregnancy, whereas 11-KT and 17α-20β-P, which were positively correlated with part immune factors, were higher during pregnancy. No negative correlations between sex steroids and immune factors were observed. In conclusion, the higher immune competence during pregnancy may indicate that parental care could improve immunity, which may

Autoimmune hepatitis in childhood: the role of genetic and immune factors.

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Ferri Liu, Priscila Menezes; de Miranda, Débora Marques; Fagundes, Eleonora Druve Tavares; Ferreira, Alexandre Rodrigues; Simões e Silva, Ana Cristina

2013-07-28

Autoimmune hepatitis (AIH) is a rare chronic inflammatory disease of the liver, which affects a group of patients who lost their immunological tolerance to antigens of the liver. It is clinically characterized by hypergammaglobulinemia, elevated liver enzymes, presence of autoantibodies and histological changes. Although being rare in children, it represents a serious cause of chronic hepatic disease that can lead to cirrhosis and hepatic failure. Clinical findings, exclusion of more common liver disorders and the detection of antibodies antinuclear antibodies, smooth muscle antibodies and anti-LKM1 are usually enough for diagnosis on clinical practice. The pathogenic mechanisms that lead to AIH remain obscure, but some research findings suggest the participation of immunologic and genetic factors. It is not yet knew the triggering factor or factors that stimulate inflammatory response. Several mechanisms proposed partially explain the immunologic findings of AIH. The knowledge of immune factors evolved might result in better markers of prognosis and response to treatment. In this review, we aim to evaluate the findings of research about genetic and immune markers and their perspectives of application in clinical practice especially in pediatric population.

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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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.

Tumor Necrosis Factor-Mediated Survival of CD169+ Cells Promotes Immune Activation during Vesicular Stomatitis Virus Infection

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Shinde, Prashant V; Xu, Haifeng C; Maney, Sathish Kumar

2018-01-01

Innate immune activation is essential to mount an effective antiviral response and to prime adaptive immunity. Although a crucial role of CD169(+) cells during vesicular stomatitis virus (VSV) infections is increasingly recognized, factors regulating CD169(+) cells during viral infections remain...... stomatitis virus infection, phagocytes produce tumor necrosis factor (TNF) which signals via TNFR1 and promote "enforced virus replication" in CD169(+) macrophages. Consequently, lack of TNF or TNFR1 resulted in defective immune activation and VSV clearance....

Common Genetic Variants Found in HLA and KIR Immune Genes in Autism Spectrum Disorder

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Anthony R Torres

2016-10-01

Full Text Available The common variant - common disease hypothesis was proposed to explain diseases with strong inheritance. This model suggests that a genetic disease is the result of the combination of several common genetic variants. Common genetic variants are described as a 5% frequency differential between diseased versus matched control populations. This theory was recently supported by an epidemiology paper stating that about 50% of genetic risk for autism resides in common variants. However, rare variants, rather than common variants, have been found in numerous genome wide genetic studies and many have concluded that the common variant—common disease hypothesis is incorrect. One interpretation is that rare variants are major contributors to genetic diseases and autism involves the interaction of many rare variants, especially in the brain. It is obvious there is much yet to be learned about autism genetics.Evidence has been mounting over the years indicating immune involvement in autism, particularly the HLA genes on chromosome 6 and KIR genes on chromosome 19. These two large multigene complexes have important immune functions and have been shown to interact to eliminate unwanted virally infected and malignant cells. HLA proteins have important functions in antigen presentation in adaptive immunity and specific epitopes on HLA class I proteins act as cognate ligands for KIR receptors in innate immunity. Data suggests that HLA alleles and KIR activating genes/haplotypes are common variants in different autism populations. For example, class I allele (HLA-A2 and HLA-G 14bp-indel frequencies are significantly increased by more than 5% over control populations (Table2. The HLA-DR4 Class II and shared epitope frequencies are significantly above the control populations (Table 2. Three activating KIR genes: 3DS1, 2DS1 and 2DS2 have increased frequencies of 15%, 22% and 14% in autism populations, respectively. There is a 6% increase in total activating KIR

Adolescent immunization rates and the effect of socio-demographic factors on immunization in a cosmopolitan city (ERZURUM) in the eastern Turkey.

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Alp, Handan; Altinkaynak, Sevin; Arikan, Duygu; Ozyazicioğlu, Nurcan

2006-04-01

Pediatric vaccinations have decreased the incidence and mortality from infectious diseases in children, but adolescents continue to be adversely affected by vaccine preventable disease. The present study was performed to determine the status of adolescents immunization and to investigate the effect of several socio-demographic factors on immunization. Using the cluster-sampling method, 817 adolescents were selected in 24 high schools (15,000 students) in central district of Erzurum (Turkey). Adolescents were categorized as completely vaccinated, incompletely vaccinated, unvaccinated or vaccination status unknown. Of the 817 adolescents, 6.9% were completely vaccinated, 24.4% were incompletely vaccinated and 64.1% were unvaccinated. The vaccination status of 4.6% of adolescents was unknown. A significantly correlation was seen between the number of siblings, the level of mother and father education, the level of parent's socio-economics status, health insurance and immunization status. Our findings indicated a small percentage of adolescents receive all of the recommended vaccine. In immunization programs in Turkey, priority should be given to increase adolescent immunization rate with a middle school and/or adolescents, vaccination.

Unbiased proteomics analysis demonstrates significant variability in mucosal immune factor expression depending on the site and method of collection.

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Kenzie M Birse

Full Text Available Female genital tract secretions are commonly sampled by lavage of the ectocervix and vaginal vault or via a sponge inserted into the endocervix for evaluating inflammation status and immune factors critical for HIV microbicide and vaccine studies. This study uses a proteomics approach to comprehensively compare the efficacy of these methods, which sample from different compartments of the female genital tract, for the collection of immune factors. Matching sponge and lavage samples were collected from 10 healthy women and were analyzed by tandem mass spectrometry. Data was analyzed by a combination of differential protein expression analysis, hierarchical clustering and pathway analysis. Of the 385 proteins identified, endocervical sponge samples collected nearly twice as many unique proteins as cervicovaginal lavage (111 vs. 61 with 55% of proteins common to both (213. Each method/site identified 73 unique proteins that have roles in host immunity according to their gene ontology. Sponge samples enriched for specific inflammation pathways including acute phase response proteins (p = 3.37×10(-24 and LXR/RXR immune activation pathways (p = 8.82×10(-22 while the role IL-17A in psoriasis pathway (p = 5.98×10(-4 and the complement system pathway (p = 3.91×10(-3 were enriched in lavage samples. Many host defense factors were differentially enriched (p<0.05 between sites including known/potential antimicrobial factors (n = 21, S100 proteins (n = 9, and immune regulatory factors such as serpins (n = 7. Immunoglobulins (n = 6 were collected at comparable levels in abundance in each site although 25% of those identified were unique to sponge samples. This study demonstrates significant differences in types and quantities of immune factors and inflammation pathways collected by each sampling technique. Therefore, clinical studies that measure mucosal immune activation or factors assessing HIV transmission should utilize

BACH transcription factors in innate and adaptive immunity.

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Igarashi, Kazuhiko; Kurosaki, Tomohiro; Roychoudhuri, Rahul

2017-07-01

BTB and CNC homology (BACH) proteins are transcriptional repressors of the basic region leucine zipper (bZIP) transcription factor family. Recent studies indicate widespread roles of BACH proteins in controlling the development and function of the innate and adaptive immune systems, including the differentiation of effector and memory cells of the B and T cell lineages, CD4 + regulatory T cells and macrophages. Here, we emphasize similarities at a molecular level in the cell-type-specific activities of BACH factors, proposing that competitive interactions of BACH proteins with transcriptional activators of the bZIP family form a common mechanistic theme underlying their diverse actions. The findings contribute to a general understanding of how transcriptional repressors shape lineage commitment and cell-type-specific functions through repression of alternative lineage programmes.

RFX Transcription Factor DAF-19 Regulates 5-HT and Innate Immune Responses to Pathogenic Bacteria in Caenorhabditis elegans

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Choi, Sunju; Xu, Lu; Sze, Ji Ying

2013-01-01

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/Ca2+/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. PMID:23505381

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

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

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. Eighty-eight and forty-six genes were found to be up- or down-regulated 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 RT-PCR. 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. PMID:16437679

Tumor necrosis factor receptor- associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system.

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Walsh, Matthew C; Lee, JangEun; Choi, Yongwon

2015-07-01

Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an adapter protein that mediates a wide array of protein-protein interactions via its TRAF domain and a RING finger domain that possesses non-conventional E3 ubiquitin ligase activity. First identified nearly two decades ago as a mediator of interleukin-1 receptor (IL-1R)-mediated activation of NFκB, TRAF6 has since been identified as an actor downstream of multiple receptor families with immunoregulatory functions, including members of the TNFR superfamily, the Toll-like receptor (TLR) family, tumor growth factor-β receptors (TGFβR), and T-cell receptor (TCR). In addition to NFκB, TRAF6 may also direct activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor pathways. In the context of the immune system, TRAF6-mediated signals have proven critical for the development, homeostasis, and/or activation of B cells, T cells, and myeloid cells, including macrophages, dendritic cells, and osteoclasts, as well as for organogenesis of thymic and secondary lymphoid tissues. In multiple cellular contexts, TRAF6 function is essential not only for proper activation of the immune system but also for maintaining immune tolerance, and more recent work has begun to identify mechanisms of contextual specificity for TRAF6, involving both regulatory protein interactions, and messenger RNA regulation by microRNAs. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Tumor necrosis factor receptor associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system

Science.gov (United States)

Walsh, Matthew C.; Lee, JangEun; Choi, Yongwon

2016-01-01

Summary Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an adaptor protein that mediates a wide array of protein-protein interactions via its TRAF domain and a RING finger domain that possesses non-conventional E3 ubiquitin ligase activity. First identified nearly two decades ago as a mediator of IL-1 receptor (IL-1R)-mediated activation of NFκB, TRAF6 has since been identified as an actor downstream of multiple receptor families with immunoregulatory functions, including members of the TNFR superfamily, the toll-like receptor (TLR) family, tumor growth factor-β receptors (TGFβR), and T cell receptor (TCR). In addition to NFκB, TRAF6 may also direct activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor (IRF) pathways. In the context of the immune system, TRAF6-mediated signals have proven critical for the development, homeostasis, and/or activation of B cells, T cells, and myeloid cells, including macrophages, dendritic cells, and osteoclasts, as well as for organogenesis of thymic and secondary lymphoid tissues. In multiple cellular contexts, TRAF6 function is essential not only for proper activation of the immune system, but also for maintaining immune tolerance, and more recent works have begun to identify mechanisms of contextual specificity for TRAF6, involving both regulatory protein interactions, and messenger RNA regulation by microRNAs. PMID:26085208

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

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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.

Target motifs affecting natural immunity by a constitutive CRISPR-Cas system in Escherichia coli.

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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.

VapC toxins from Mycobacterium tuberculosis are ribonucleases that differentially inhibit growth and are neutralized by cognate VapB antitoxins.

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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.

Memory CD8+ T Cells: Orchestrators and Key Players of Innate Immunity?

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Grégoire Lauvau

2016-09-01

Full Text Available Over the past decades, the dichotomy between innate and adaptive immune responses has largely dominated our understanding of immunology. Upon primary encounter with microbial pathogens, differentiation of adaptive immune cells into functional effectors usually takes several days or even longer, making them contribute to host protection only late during primary infection. However, once generated, antigen-experienced T lymphocytes can persist in the organism and constitute a pool of memory cells that mediate fast and effective protection to a recall infection with the same microbial pathogen. Herein, we challenge this classical paradigm by highlighting the "innate nature" of memory CD8+ T cells. First, within the thymus or in the periphery, naïve CD8+ T cells may acquire phenotypic and functional characteristics of memory CD8+ T cells independently of challenge with foreign antigens. Second, both the "unconventional" and the "conventional" memory cells can rapidly express protective effector functions in response to sets of inflammatory cytokines and chemokines signals, independent of cognate antigen triggering. Third, memory CD8+ T cells can act by orchestrating the recruitment, activation, and licensing of innate cells, leading to broad antimicrobial states. Thus, collectively, memory CD8+ T cells may represent important actors of innate immune defenses.

Using Human Factors Techniques to Design Text Message Reminders for Childhood Immunization

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Ahlers-Schmidt, Carolyn R.; Hart, Traci; Chesser, Amy; Williams, Katherine S.; Yaghmai, Beryl; Shah-Haque, Sapna; Wittler, Robert R.

2012-01-01

This study engaged parents to develop concise, informative, and comprehensible text messages for an immunization reminder system using Human Factors techniques. Fifty parents completed a structured interview including demographics, technology questions, willingness to receive texts from their child's doctor, and health literacy. Each participant…

Radio immune analysis of endocrine system state at exposure to different physical factors

International Nuclear Information System (INIS)

Rozdyil's'ka, O.M.; Rozdtil's'kij, S.Yi.; Bratchuk, O.M.; Yakimova, T.P.

1999-01-01

Radio immune analysis allows to define more exactly the mechanisms of physical factors action and may be used for validation of new therapeutic techniques. The ultra-high frequency magneto therapy, sinusoid modulated current and direct current influence the state of the endocrine system differently but within the physiological norm. The most prominent action of the physical factor is observed at trans cerebral mode

Innovative Approaches for Immune Tolerance to Factor VIII in the Treatment of Hemophilia A

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Sherman, Alexandra; Biswas, Moanaro; Herzog, Roland W.

2017-01-01

Hemophilia A (coagulation factor VIII deficiency) is a debilitating genetic disorder that is primarily treated with intravenous replacement therapy. Despite a variety of factor VIII protein formulations available, the risk of developing anti-dug antibodies (“inhibitors”) remains. Overall, 20–30% of patients with severe disease develop inhibitors. Current clinical immune tolerance induction protocols to eliminate inhibitors are not effective in all patients, and there are no prophylactic protocols to prevent the immune response. New experimental therapies, such as gene and cell therapies, show promising results in pre-clinical studies in animal models of hemophilia. Examples include hepatic gene transfer with viral vectors, genetically engineered regulatory T cells (Treg), in vivo Treg induction using immune modulatory drugs, and maternal antigen transfer. Furthermore, an oral tolerance protocol is being developed based on transgenic lettuce plants, which suppressed inhibitor formation in hemophilic mice and dogs. Hopefully, some of these innovative approaches will reduce the risk of and/or more effectively eliminate inhibitor formation in future treatment of hemophilia A. PMID:29225598

Bacteria-triggered systemic immunity in barley is associated with WRKY and ETHYLENE RESPONSIVE FACTORs but not with salicylic acid.

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Dey, Sanjukta; Wenig, Marion; Langen, Gregor; Sharma, Sapna; Kugler, Karl G; Knappe, Claudia; Hause, Bettina; Bichlmeier, Marlies; Babaeizad, Valiollah; Imani, Jafargholi; Janzik, Ingar; Stempfl, Thomas; Hückelhoven, Ralph; Kogel, Karl-Heinz; Mayer, Klaus F X; Vlot, A Corina

2014-12-01

Leaf-to-leaf systemic immune signaling known as systemic acquired resistance is poorly understood in monocotyledonous plants. Here, we characterize systemic immunity in barley (Hordeum vulgare) triggered after primary leaf infection with either Pseudomonas syringae pathovar japonica (Psj) or Xanthomonas translucens pathovar cerealis (Xtc). Both pathogens induced resistance in systemic, uninfected leaves against a subsequent challenge infection with Xtc. In contrast to systemic acquired resistance in Arabidopsis (Arabidopsis thaliana), systemic immunity in barley was not associated with NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 or the local or systemic accumulation of salicylic acid. Instead, we documented a moderate local but not systemic induction of abscisic acid after infection of leaves with Psj. In contrast to salicylic acid or its functional analog benzothiadiazole, local applications of the jasmonic acid methyl ester or abscisic acid triggered systemic immunity to Xtc. RNA sequencing analysis of local and systemic transcript accumulation revealed unique gene expression changes in response to both Psj and Xtc and a clear separation of local from systemic responses. The systemic response appeared relatively modest, and quantitative reverse transcription-polymerase chain reaction associated systemic immunity with the local and systemic induction of two WRKY and two ETHYLENE RESPONSIVE FACTOR (ERF)-like transcription factors. Systemic immunity against Xtc was further associated with transcriptional changes after a secondary/systemic Xtc challenge infection; these changes were dependent on the primary treatment. Taken together, bacteria-induced systemic immunity in barley may be mediated in part by WRKY and ERF-like transcription factors, possibly facilitating transcriptional reprogramming to potentiate immunity. © 2014 American Society of Plant Biologists. All Rights Reserved.

Factors associated with routine immunization coverage of children under one year old in Lao People's Democratic Republic.

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Phoummalaysith, Bounfeng; Yamamoto, Eiko; Xeuatvongsa, Anonh; Louangpradith, Viengsakhone; Keohavong, Bounxou; Saw, Yu Mon; Hamajima, Nobuyuki

2018-05-03

Routine vaccination is administered free of charge to all children under one year old in Lao People's Democratic Republic (Lao PDR) and the national goal is to achieve at least 95% coverage with all vaccines included in the national immunization program by 2025. In this study, factors related to the immunization system and characteristics of provinces and districts in Lao PDR were examined to evaluate the association with routine immunization coverage. Coverage rates for Bacillus Calmette-Guerin (BCG), Diphtheria-Tetanus-Pertussis-Hepatitis B (DTP-HepB), DTP-HepB-Hib (Haemophilus influenzae type B), polio (OPV), and measles (MCV1) vaccines from 2002 to 2014 collected through regular reporting system, were used to identify the immunization coverage trends in Lao PDR. Correlation analysis was performed using immunization coverage, characteristics of provinces or districts (population, population density, and proportion of poor villages and high-risk villages), and factors related to immunization service (including the proportions of the following: villages served by health facility levels, vaccine session types, and presence of well-functioning cold chain equipment). To determine factors associated with low coverage, provinces were categorized based on 80% of DTP-HepB-Hib3 coverage (<80% = low group; ≥80% = high group). Coverages of BCG, DTP-HepB3, OPV3 and MCV1 increased gradually from 2007 to 2014 (82.2-88.3% in 2014). However, BCG coverage showed the least improvement from 2002 to 2014. The coverage of each vaccine correlated with the coverage of the other vaccines and DTP-HepB-Hib dropout rate in provinces as well as districts. The provinces with low immunization coverage were correlated with higher proportions of poor villages. Routine immunization coverage has been improving in the last 13 years, but the national goal is not yet reached in Lao PDR. The results of this study suggest that BCG coverage and poor villages should be targeted to improve

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.

RStrucFam: a web server to associate structure and cognate RNA for RNA-binding proteins from sequence information.

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Ghosh, Pritha; Mathew, Oommen K; Sowdhamini, Ramanathan

2016-10-07

RNA-binding proteins (RBPs) interact with their cognate RNA(s) to form large biomolecular assemblies. They are versatile in their functionality and are involved in a myriad of processes inside the cell. RBPs with similar structural features and common biological functions are grouped together into families and superfamilies. It will be useful to obtain an early understanding and association of RNA-binding property of sequences of gene products. Here, we report a web server, RStrucFam, to predict the structure, type of cognate RNA(s) and function(s) of proteins, where possible, from mere sequence information. The web server employs Hidden Markov Model scan (hmmscan) to enable association to a back-end database of structural and sequence families. The database (HMMRBP) comprises of 437 HMMs of RBP families of known structure that have been generated using structure-based sequence alignments and 746 sequence-centric RBP family HMMs. The input protein sequence is associated with structural or sequence domain families, if structure or sequence signatures exist. In case of association of the protein with a family of known structures, output features like, multiple structure-based sequence alignment (MSSA) of the query with all others members of that family is provided. Further, cognate RNA partner(s) for that protein, Gene Ontology (GO) annotations, if any and a homology model of the protein can be obtained. The users can also browse through the database for details pertaining to each family, protein or RNA and their related information based on keyword search or RNA motif search. RStrucFam is a web server that exploits structurally conserved features of RBPs, derived from known family members and imprinted in mathematical profiles, to predict putative RBPs from sequence information. Proteins that fail to associate with such structure-centric families are further queried against the sequence-centric RBP family HMMs in the HMMRBP database. Further, all other essential

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

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Simon Heidegger

Full Text Available 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.

High resolution crystal structure of PedB: a structural basis for the classification of pediocin-like immunity proteins

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Cha Sun-Shin

2007-05-01

Full Text Available Abstract Background Pediocin-like bacteriocins, ribosomally-synthesized antimicrobial peptides, are generally coexpressed with cognate immunity proteins in order to protect the bacteriocin-producer from its own bacteriocin. As a step for understanding the mode of action of immunity proteins, we determined the crystal structure of PedB, a pediocin-like immunity protein conferring immunity to pediocin PP-1. Results The 1.6 Å crystal structure of PedB reveals that PedB consists of an antiparallel four-helix bundle with a flexible C-terminal end. PedB shows structural similarity to an immunity protein against enterocin A (EntA-im but some disparity to an immunity protein against carnobacteriocin B2 (ImB2 in both the C-terminal conformation and the local structure constructed by α3, α4, and their connecting loop. Structure-inspired mutational studies reveal that deletion of the last seven residues of the C-terminus of PedB almost abolished its immunity activity. Conclusion The fact that PedB, EntA-im, and ImB2 share a four-helix bundle structure strongly suggests the structural conservation of this motif in the pediocin-like immunity proteins. The significant difference in the core structure and the C-terminal conformation provides a structural basis for the classification of pediocin-like immunity proteins. Our mutational study using C-terminal-shortened PedBs and the investigation of primary sequence of the C-terminal region, propose that several polar or charged residues in the extreme C-terminus of PedB which is crucial for the immunity are involved in the specific recognition of pediocin PP-1.

CRISPR-Cas: evolution of an RNA-based adaptive immunity system in prokaryotes.

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Koonin, Eugene V; Makarova, Kira S

2013-05-01

The CRISPR-Cas (clustered regularly interspaced short palindromic repeats, CRISPR-associated genes) is an adaptive immunity system in bacteria and archaea that functions via a distinct self-non-self recognition mechanism that is partially analogous to the mechanism of eukaryotic RNA interference (RNAi). The CRISPR-Cas system incorporates fragments of virus or plasmid DNA into the CRISPR repeat cassettes and employs the processed transcripts of these spacers as guide RNAs to cleave the cognate foreign DNA or RNA. The Cas proteins, however, are not homologous to the proteins involved in RNAi and comprise numerous, highly diverged families. The majority of the Cas proteins contain diverse variants of the RNA recognition motif (RRM), a widespread RNA-binding domain. Despite the fast evolution that is typical of the cas genes, the presence of diverse versions of the RRM in most Cas proteins provides for a simple scenario for the evolution of the three distinct types of CRISPR-cas systems. In addition to several proteins that are directly implicated in the immune response, the cas genes encode a variety of proteins that are homologous to prokaryotic toxins that typically possess nuclease activity. The predicted toxins associated with CRISPR-Cas systems include the essential Cas2 protein, proteins of COG1517 that, in addition to a ligand-binding domain and a helix-turn-helix domain, typically contain different nuclease domains and several other predicted nucleases. The tight association of the CRISPR-Cas immunity systems with predicted toxins that, upon activation, would induce dormancy or cell death suggests that adaptive immunity and dormancy/suicide response are functionally coupled. Such coupling could manifest in the persistence state being induced and potentially providing conditions for more effective action of the immune system or in cell death being triggered when immunity fails.

Directed evolution of human T cell receptor CDR2 residues by phage display dramatically enhances affinity for cognate peptide-MHC without increasing apparent cross-reactivity

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Dunn, Steven M.; Rizkallah, Pierre J.; Baston, Emma; Mahon, Tara; Cameron, Brian; Moysey, Ruth; Gao, Feng; Sami, Malkit; Boulter, Jonathan; Li, Yi; Jakobsen, Bent K.

2006-01-01

The mammalian α/β T cell receptor (TCR) repertoire plays a pivotal role in adaptive immunity by recognizing short, processed, peptide antigens bound in the context of a highly diverse family of cell-surface major histocompatibility complexes (pMHCs). Despite the extensive TCR–MHC interaction surface, peptide-independent cross-reactivity of native TCRs is generally avoided through cell-mediated selection of molecules with low inherent affinity for MHC. Here we show that, contrary to expectations, the germ line-encoded complementarity determining regions (CDRs) of human TCRs, namely the CDR2s, which appear to contact only the MHC surface and not the bound peptide, can be engineered to yield soluble low nanomolar affinity ligands that retain a surprisingly high degree of specificity for the cognate pMHC target. Structural investigation of one such CDR2 mutant implicates shape complementarity of the mutant CDR2 contact interfaces as being a key determinant of the increased affinity. Our results suggest that manipulation of germ line CDR2 loops may provide a useful route to the production of high-affinity TCRs with therapeutic and diagnostic potential. PMID:16600963

Involvement of Corticotropin-Releasing Factor and Receptors in Immune Cells in Irritable Bowel Syndrome

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Mahanand Chatoo

2018-02-01

Full Text Available Irritable bowel syndrome (IBS is a common functional gastrointestinal disorder defined by ROME IV criteria as pain in the lower abdominal region, which is associated with altered bowel habit or defecation. The underlying mechanism of IBS is not completely understood. IBS seems to be a product of interactions between various factors with genetics, dietary/intestinal microbiota, low-grade inflammation, and stress playing a key role in the pathogenesis of this disease. The crosstalk between the immune system and stress in IBS mechanism is increasingly recognized. Corticotropin-releasing factor (CRF, a major mediator in the stress response, is involved in altered function in GI, including inflammatory processes, colonic transit time, contractile activity, defecation pattern, pain threshold, mucosal secretory function, and barrier functions. This mini review focuses on the recently establish local GI-CRF system, its involvement in modulating the immune response in IBS, and summarizes current IBS animal models and mapping of CRF, CRFR1, and CRFR2 expression in colon tissues. CRF and receptors might be a key molecule involving the immune and movement function via brain–gut axis in IBS.

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

Breast cancer is the most common cancer in women worldwide and metastatic dissemination is the principal factor related to death by this disease. Breast cancer stem cells (bCSC) are thought to be responsible for metastasis and chemoresistance. In this study, based on whole transcriptome analysis...... 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....... 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...

Factors associated with maternal influenza immunization decision-making. Evidence of immunization history and message framing effects.

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Frew, Paula M; Owens, Lauren E; Saint-Victor, Diane S; Benedict, Samantha; Zhang, Siyu; Omer, Saad B

2014-01-01

We examined pregnant women's intention to obtain the seasonal influenza vaccine via a randomized controlled study examining the effects of immunization history, message exposure, and sociodemographic correlates. Pregnant women ages 18-50 participated in a randomized message framing study from September 2011 through May 2012. Venue-based sampling was used to recruit racial and ethnic minority women throughout Atlanta, Georgia. Key outcomes were evaluated using bivariate and multivariate analyses. History of influenza immunization was positively associated with intent to immunize during pregnancy [OR=2.31, 90%CI: (1.06, 5.00)]. Significant correlates of intention to immunize included perceived susceptibility to influenza during pregnancy [OR=3.8, 90% CI: (1.75, 8.36)] and vaccine efficacy [OR=10.53, 90% CI: (4.34, 25.50)]. Single message exposure did not influence a woman's intent to vaccinate. Prior immunization, perceived flu susceptibility and perceived vaccine effectiveness promoted immunization intent among this population of pregnant minority women. Vaccine efficacy and disease susceptibility are critical to promoting immunization among women with no history of seasonal influenza immunization, while those who received the vaccine are likely to do so again. These findings provide evidence for the promotion of repeated exposure to vaccine messages emphasizing vaccine efficacy, normative support, and susceptibility to influenza.

Platelet activating factor receptor binding plays a critical role in jet fuel-induced immune suppression

International Nuclear Information System (INIS)

Ramos, Gerardo; Kazimi, Nasser; Nghiem, Dat X.; Walterscheid, Jeffrey P.; Ullrich, Stephen E.

2004-01-01

Applying military jet fuel (JP-8) or commercial jet fuel (Jet-A) to the skin of mice suppresses the immune response in a dose-dependant manner. The release of biological response modifiers, particularly prostaglandin E 2 (PGE 2 ), is a critical step in activating immune suppression. Previous studies have shown that injecting selective cyclooxygenase-2 inhibitors into jet fuel-treated mice blocks immune suppression. Because the inflammatory phospholipid mediator, platelet-activating factor (PAF), up-regulates cyclooxygenase-2 production and PGE 2 synthesis by keratinocytes, we tested the hypothesis that PAF-receptor binding plays a role in jet fuel-induced immune suppression. Treating keratinocyte cultures with PAF and/or jet fuel (JP-8 and Jet-A) stimulates PGE 2 secretion. Jet fuel-induced PGE 2 production was suppressed by treating the keratinocytes with specific PAF-receptor antagonists. Injecting mice with PAF, or treating the skin of the mice with JP-8, or Jet-A, induced immune suppression. Jet fuel-induced immune suppression was blocked when the jet fuel-treated mice were injected with PAF-receptor antagonists before treatment. Jet fuel treatment has been reported to activate oxidative stress and treating the mice with anti-oxidants (Vitamins C, or E or beta-hydroxy toluene), before jet fuel application, interfered with immune suppression. These findings confirm previous studies showing that PAF-receptor binding can modulate immune function. Furthermore, they suggest that PAF-receptor binding may be an early event in the induction of immune suppression by immunotoxic environmental agents that target the skin

Regulation of anti-Plasmodium immunity by a LITAF-like transcription factor in the malaria vector Anopheles gambiae.

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Ryan C Smith

Full Text Available The mosquito is the obligate vector for malaria transmission. To complete its development within the mosquito, the malaria parasite Plasmodium must overcome the protective action of the mosquito innate immune system. Here we report on the involvement of the Anopheles gambiae orthologue of a conserved component of the vertebrate immune system, LPS-induced TNFα transcription factor (LITAF, and its role in mosquito anti-Plasmodium immunity. An. gambiae LITAF-like 3 (LL3 expression is up-regulated in response to midgut invasion by both rodent and human malaria parasites. Silencing of LL3 expression greatly increases parasite survival, indicating that LL3 is part of an anti-Plasmodium defense mechanism. Electrophoretic mobility shift assays identified specific LL3 DNA-binding motifs within the promoter of SRPN6, a gene that also mediates mosquito defense against Plasmodium. Further experiments indicated that these motifs play a direct role in LL3 regulation of SRPN6 expression. We conclude that LL3 is a transcription factor capable of modulating SRPN6 expression as part of the mosquito anti-Plasmodium immune response.

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

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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.

The intracellular immune receptor Rx1 regulates the DNA-binding activity of a Golden2-like transcription factor

NARCIS (Netherlands)

Townsend, Philip D.; Dixon, Christopher H.; Slootweg, Erik J.; Sukarta, Octavina C.A.; Yang, Ally W.H.; Hughes, Timothy R.; Sharples, Gary J.; Palsson, Lars-Olof; Takken, Frank L.W.; Goverse, Aska; Cann, Martin J.

2018-01-01

Plant NLR proteins enable the immune system to recognise and respond to pathogen attack. An early consequence of immune activation is transcriptional reprogramming and some NLRs have been shown to act in the nucleus and interact with transcription factors. The Rx1 NLR protein of potato is further

The Potato Nucleotide-binding Leucine-rich Repeat (NLR) Immune Receptor Rx1 Is a Pathogen-dependent DNA-deforming Protein*

Science.gov (United States)

Fenyk, Stepan; Townsend, Philip D.; Dixon, Christopher H.; Spies, Gerhard B.; de San Eustaquio Campillo, Alba; Slootweg, Erik J.; Westerhof, Lotte B.; Gawehns, Fleur K. K.; Knight, Marc R.; Sharples, Gary J.; Goverse, Aska; Pålsson, Lars-Olof; Takken, Frank L. W.; Cann, Martin J.

2015-01-01

Plant nucleotide-binding leucine-rich repeat (NLR) proteins enable cells to respond to pathogen attack. Several NLRs act in the nucleus; however, conserved nuclear targets that support their role in immunity are unknown. Previously, we noted a structural homology between the nucleotide-binding domain of NLRs and DNA replication origin-binding Cdc6/Orc1 proteins. Here we show that the NB-ARC (nucleotide-binding, Apaf-1, R-proteins, and CED-4) domain of the Rx1 NLR of potato binds nucleic acids. Rx1 induces ATP-dependent bending and melting of DNA in vitro, dependent upon a functional P-loop. In situ full-length Rx1 binds nuclear DNA following activation by its cognate pathogen-derived effector protein, the coat protein of potato virus X. In line with its obligatory nucleocytoplasmic distribution, DNA binding was only observed when Rx1 was allowed to freely translocate between both compartments and was activated in the cytoplasm. Immune activation induced by an unrelated NLR-effector pair did not trigger an Rx1-DNA interaction. DNA binding is therefore not merely a consequence of immune activation. These data establish a role for DNA distortion in Rx1 immune signaling and define DNA as a molecular target of an activated NLR. PMID:26306038

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

THE BIOTIC FACTOR OF TREMATOD OPISTHORHIS FELINEUS INVASION INFLUENCE ON HOST IMMUNE STATUS AND SOMATIC CELLS PROLIFERATIVE ACTIVITY

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A. G. Rybka

2016-01-01

Full Text Available The paper confirms long-time opisthorhis invasion role as a risk factor of host immune system reconstitution as well as an important factor in holangiocarcinomas development. It was shown that opisthorhosis invasion primal stage induce host immune system reconstitution. Host immune B-cells system is activated by metacercaria antigens, while the same antigens inhibits T-cells activity. Opisthorhis metabolites stimulate proliferative mithogen-induced T-cells acti vity. Chronic opisthorchis invasion leads to immune system disbalance. It means: decrease of specific and non-speci fic natural killers activity, number of high proliferative activity T-lymphocytes and the shift of regulatory T-cells subset to suppressors prevalence. At the same time specific as well as non-specific T-suppressors functional ability is very low. It was shown T-cells helper-amplifier activation. Despite of circulating B-cells decrease the antibody produced cells number is spleen increases significantly at the same time with circulating immune complexes accumulation. Even 3–6 month after dehelmintisation the immune system disbalance decreases but lefts. In addition, chronic opisthorhis invasion leads to the proliferative processes activation in ductal epithelium, liver, lymph nodes and in other organs which leads to cancer proliferation. According to the results obtained the opisthorhis infected patients needs to be immunocorrected before as well as after dehelmintisation for holangiocancerogenesis profylaxis.

Les verbes à objets cognats en portugais européen : quelques réflexions sur la conversion et la génération de mots

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Celda Morgado Choupina

2013-01-01

Full Text Available The text analyzes the verbs with cognate objects in European Portuguese and provides an analysis of this phenomenon in the framework of Distributed Morphology, and a few ideas of the Minimalist Program. In this paper we only develop the analysis of the constructions of the type of chorar um choro... [cry a cry…] and cantar uma cantiga [sing a song]. Since a lexicalist theory as the one developed by Hale e Keyser (1993; 2002 can’t solve all the issues raised by the various types of constructions in EP, we will try an analysis that combines the contributions of Haugen (2009, on cognate objects, Marantz (1993 and Alexiadou (2001, 2006, on verbal functional heads, and (Chomsky 1995, on the idea of movement by copy

The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression.

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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

Cloning and characterization of carboxyl terminus of heat shock cognate 70-interacting protein gene from the silkworm, Bombyx mori.

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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. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Latin, the Key to English Vocabulary. A Gamebook on English Derivatives and Cognates to Accompany "Voces de Olympo" (Echoes from Mt. Olympus).

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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…

[Study on the immunization status and its influencing factors among workers from the polio network laboratories in China].

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Guo, Y S; Wang, J Q; Xu, C; Liu, Y N; He, X H; Wei, Q

2017-06-10

Objective: To Investigate the immune status and influencing factors of provincial polio network laboratory (PNL) workers in China so as to provide evidence for the development of related strategies to protect personnel working at the PNLs. Methods: All the practitioners from the PNLs at the provincial centers for disease control, were selected as objects for this study, from October to December, 2016, under a questionnaire survey. Information on status of immunity and influencing factors was collected, with SAS software, trend chi-square used for statistics analysis. Results: A total of 77 workers were involved in this survey, with 60 (78 % ) of them completed the polio-based immune program but the rest 17 (22 % ) remained records unclear. 66 people (about 86 % ) remembered clearly that they had received vaccination when engaging in the polio-lab work, but the rest 11 (14 % ) with only partial vaccination records. We also noticed that the Influencing factors realted to vaccination status were: age ( χ (2)=2.48, P polio-related vaccination, with 41 % of them completed a 3-time inoculation program, when started working in this field.

Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells

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Göbel, Kerstin; Pankratz, Susann; Asaridou, Chloi-Magdalini; Herrmann, Alexander M.; Bittner, Stefan; Merker, Monika; Ruck, Tobias; Glumm, Sarah; Langhauser, Friederike; Kraft, Peter; Krug, Thorsten F.; Breuer, Johanna; Herold, Martin; Gross, Catharina C.; Beckmann, Denise; Korb-Pap, Adelheid; Schuhmann, Michael K.; Kuerten, Stefanie; Mitroulis, Ioannis; Ruppert, Clemens; Nolte, Marc W.; Panousis, Con; Klotz, Luisa; Kehrel, Beate; Korn, Thomas; Langer, Harald F.; Pap, Thomas; Nieswandt, Bernhard; Wiendl, Heinz; Chavakis, Triantafyllos; Kleinschnitz, Christoph; Meuth, Sven G.

2016-01-01

Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein–kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells. Immune activation by FXII is mediated by dendritic cells in a CD87-dependent manner and involves alterations in intracellular cyclic AMP formation. Our study demonstrates that a member of the plasmatic coagulation cascade is a key mediator of autoimmunity. FXII inhibition may provide a strategy to combat MS and other immune-related disorders. PMID:27188843

Innate immune humoral factors, C1q and factor H, with differential pattern recognition properties, alter macrophage response to carbon nanotubes.

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Pondman, Kirsten M; Pednekar, Lina; Paudyal, Basudev; Tsolaki, Anthony G; Kouser, Lubna; Khan, Haseeb A; Shamji, Mohamed H; Ten Haken, Bennie; Stenbeck, Gudrun; Sim, Robert B; Kishore, Uday

2015-11-01

Interaction between the complement system and carbon nanotubes (CNTs) can modify their intended biomedical applications. Pristine and derivatised CNTs can activate complement primarily via the classical pathway which enhances uptake of CNTs and suppresses pro-inflammatory response by immune cells. Here, we report that the interaction of C1q, the classical pathway recognition molecule, with CNTs involves charge pattern and classical pathway activation that is partly inhibited by factor H, a complement regulator. C1q and its globular modules, but not factor H, enhanced uptake of CNTs by macrophages and modulated the pro-inflammatory immune response. Thus, soluble complement factors can interact differentially with CNTs and alter the immune response even without complement activation. Coating CNTs with recombinant C1q globular heads offers a novel way of controlling classical pathway activation in nanotherapeutics. Surprisingly, the globular heads also enhance clearance by phagocytes and down-regulate inflammation, suggesting unexpected complexity in receptor interaction. Carbon nanotubes (CNTs) maybe useful in the clinical setting as targeting drug carriers. However, it is also well known that they can interact and activate the complement system, which may have a negative impact on the applicability of CNTs. In this study, the authors functionalized multi-walled CNT (MWNT), and investigated the interaction with the complement pathway. These studies are important so as to gain further understanding of the underlying mechanism in preparation for future use of CNTs in the clinical setting. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Pro-tumorigenic effects of transforming growth factor beta 1 in canine osteosarcoma.

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Portela, R F; Fadl-Alla, B A; Pondenis, H C; Byrum, M L; Garrett, L D; Wycislo, K L; Borst, L B; Fan, T M

2014-01-01

Transforming growth factor beta 1 (TGFβ1) is a pleiotropic cytokine that contributes to reparative skeletal remodeling by inducing osteoblast proliferation, migration, and angiogenesis. Organic bone matrix is the largest bodily reservoir for latent TGFβ1, and active osteoblasts express cognate receptors for TGFβ1 (TGFβRI and TGFβRII). During malignant osteolysis, TGFβ1 is liberated from eroded bone matrix and promotes local progression of osteotropic solid tumors by its mitogenic and prosurvival activities. Canine osteosarcoma (OS) cells will possess TGFβ1 signaling machinery. Blockade of TGFβ1 signaling will attenuate pro-tumorigenic activities in OS cells. Naturally occurring primary OS samples will express cognate TGFβ1 receptors; and in dogs with OS, focal malignant osteolysis will contribute to circulating TGFβ1 concentrations. Thirty-three dogs with appendicular OS. Expression of TGFβ1 and its cognate receptors, as well as the biologic effects of TGFβ1 blockade, was characterized in OS cells. Ten spontaneous OS samples were characterized for TGFβRI/II expressions by immunohistochemistry. In 33 dogs with OS, plasma TGFβ1 concentrations were quantified and correlated with bone resorption. Canine OS cells secrete TGFβ1, express cognate receptors, and TGFβ1 signaling blockade decreases proliferation, migration, and vascular endothelial growth factor secretion. Naturally occurring OS samples abundantly and uniformly express TGFβRI/II, and in OS-bearing dogs, circulating TGFβ1 concentrations correlate with urine N-telopeptide excretion. Canine OS cells possess TGFβ1 signaling machinery, potentially allowing for the establishment of an autocrine and paracrine pro-tumorigenic signaling loop. As such, TGFβ1 inhibitors might impede localized OS progression in dogs. Copyright © 2014 by the American College of Veterinary Internal Medicine.

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

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Yin, Jinghua; Zhang, Jian; Lu, Qianjin

2017-07-01

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

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

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

2017-08-01

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

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

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B P Muzah

2012-10-01

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

Timely immunization completion among children in Vietnam from 2000 to 2011: a multilevel analysis of individual and contextual factors

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Dao Thi Minh An

2016-02-01

Full Text Available Background: Since the beginning of 2014, there have been nearly 6,000 confirmed measles cases in northern Vietnam. Of these, more than 86% had neither been immunized nor was their vaccination status confirmed. Objective: To establish the likelihood that children under five in Vietnam had ‘timely immunization completion’ (2000–2011 and identify factors that account for variations in timely immunization completion. Design: Secondary data from the Multiple Indicator Cluster Survey (MICS, which sampled women aged 15–49 from the 1999 Vietnamese Population and Housing Census frame, were analyzed. Multilevel analysis using Poisson regression was undertaken. Results: Proportions of children under five who had timely immunization completion were low, especially for HBV dose 2 and HBV dose 3, which decreased between 2000 and 2011. Among seven vaccines used in the National Expanded Program of Immunization (EPI in 2000, 2006, and 2011, measles dose 1 had the highest timely immunization completion at 65.3%, 66.7%, and 73.6%, respectively, and hepatitis B dose 1 had the lowest at 17.5%, 19.3%, and 45.5%, respectively. Timely immunization completion was less common among children whose mothers had relatively less household wealth, were from ethnic minorities, lived in rural areas, and had less education. At the community level, the child's region of residence was the main predictor of timely immunization completion, and the availability of hospital delivery and community prenatal care in the local community were also determinants. Conclusion: The EPI should include ‘timely immunization completion’ as a quality indicator. There should also be greater focus and targeting in rural areas, and among women who have relatively low education, belong to minority groups, and have less household wealth. Further research on this topic using multilevel analysis is needed to better understand how these factors interact.

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...

Bacteria-Triggered Systemic Immunity in Barley Is Associated with WRKY and ETHYLENE RESPONSIVE FACTORs But Not with Salicylic Acid1[C][W

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Dey, Sanjukta; Wenig, Marion; Langen, Gregor; Sharma, Sapna; Kugler, Karl G.; Knappe, Claudia; Hause, Bettina; Bichlmeier, Marlies; Babaeizad, Valiollah; Imani, Jafargholi; Janzik, Ingar; Stempfl, Thomas; Hückelhoven, Ralph; Kogel, Karl-Heinz; Mayer, Klaus F.X.

2014-01-01

Leaf-to-leaf systemic immune signaling known as systemic acquired resistance is poorly understood in monocotyledonous plants. Here, we characterize systemic immunity in barley (Hordeum vulgare) triggered after primary leaf infection with either Pseudomonas syringae pathovar japonica (Psj) or Xanthomonas translucens pathovar cerealis (Xtc). Both pathogens induced resistance in systemic, uninfected leaves against a subsequent challenge infection with Xtc. In contrast to systemic acquired resistance in Arabidopsis (Arabidopsis thaliana), systemic immunity in barley was not associated with NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 or the local or systemic accumulation of salicylic acid. Instead, we documented a moderate local but not systemic induction of abscisic acid after infection of leaves with Psj. In contrast to salicylic acid or its functional analog benzothiadiazole, local applications of the jasmonic acid methyl ester or abscisic acid triggered systemic immunity to Xtc. RNA sequencing analysis of local and systemic transcript accumulation revealed unique gene expression changes in response to both Psj and Xtc and a clear separation of local from systemic responses. The systemic response appeared relatively modest, and quantitative reverse transcription-polymerase chain reaction associated systemic immunity with the local and systemic induction of two WRKY and two ETHYLENE RESPONSIVE FACTOR (ERF)-like transcription factors. Systemic immunity against Xtc was further associated with transcriptional changes after a secondary/systemic Xtc challenge infection; these changes were dependent on the primary treatment. Taken together, bacteria-induced systemic immunity in barley may be mediated in part by WRKY and ERF-like transcription factors, possibly facilitating transcriptional reprogramming to potentiate immunity. PMID:25332505

Parental concern about vaccine safety in Canadian children partially immunized at age 2: a multivariable model including system level factors.

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MacDonald, Shannon E; Schopflocher, Donald P; Vaudry, Wendy

2014-01-01

Children who begin but do not fully complete the recommended series of childhood vaccines by 2 y of age are a much larger group than those who receive no vaccines. While parents who refuse all vaccines typically express concern about vaccine safety, it is critical to determine what influences parents of 'partially' immunized children. This case-control study examined whether parental concern about vaccine safety was responsible for partial immunization, and whether other personal or system-level factors played an important role. A random sample of parents of partially and completely immunized 2 y old children were selected from a Canadian regional immunization registry and completed a postal survey assessing various personal and system-level factors. Unadjusted odds ratios (OR) and adjusted ORs (aOR) were calculated with logistic regression. While vaccine safety concern was associated with partial immunization (OR 7.338, 95% CI 4.138-13.012), other variables were more strongly associated and reduced the strength of the relationship between concern and partial immunization in multivariable analysis (aOR 2.829, 95% CI 1.151-6.957). Other important factors included perceived disease susceptibility and severity (aOR 4.629, 95% CI 2.017-10.625), residential mobility (aOR 3.908, 95% CI 2.075-7.358), daycare use (aOR 0.310, 95% CI 0.144-0.671), number of needles administered at each visit (aOR 7.734, 95% CI 2.598-23.025) and access to a regular physician (aOR 0.219, 95% CI 0.057-0.846). While concern about vaccine safety may be addressed through educational strategies, this study suggests that additional program and policy-level strategies may positively impact immunization uptake.

Differential susceptibility of HIV strains to innate immune factors in human cervical-vaginal secretions

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Mimi Ghosh

2010-07-01

Full Text Available Mimi Ghosh, John V Fahey, Charles R WiraDepartment of Physiology and Neurobiology, Dartmouth Medical School, Lebanon, New Hampshire, USAAbstract: The female reproductive tract (FRT is protected by innate and adaptive immune mechanisms, which work in concert to defend against human immunodeficiency virus (HIV and other sexually transmitted infections (STIs. Under the control of sex hormones throughout a woman’s life, the immune system in the FRT has evolved to meet the challenges of protection against STIs, coupled with the need to sustain the development of new life. The studies presented in this review focus on the threat of HIV infection and the levels of protection present in the FRT during the menstrual cycle. Studies from our laboratory and others, examined the presence and variability of immune components against viral infection in the FRT. Our findings indicate that there are some factors in the FRT secretions that inhibit and enhance infectivity of individual strains of HIV. Given the complexities of hormonal regulation, identification of the elements involved in susceptibility to and protection against HIV in women must involve a careful analysis of transmitted viruses and a clear understanding of immune protection in the FRT.Keywords: HIV susceptibility, CVL

Lexical and semantic representations of L2 cognate and noncognate words acquisition in children : evidence from two learning methods

OpenAIRE

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

2012-01-01

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 analyze the effect of two learning methods (picture-based vs. word-based method) and two types of words (cognates and noncognates) 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....

The Potato Nucleotide-binding Leucine-rich Repeat (NLR) Immune Receptor Rx1 Is a Pathogen-dependent DNA-deforming Protein.

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Fenyk, Stepan; Townsend, Philip D; Dixon, Christopher H; Spies, Gerhard B; de San Eustaquio Campillo, Alba; Slootweg, Erik J; Westerhof, Lotte B; Gawehns, Fleur K K; Knight, Marc R; Sharples, Gary J; Goverse, Aska; Pålsson, Lars-Olof; Takken, Frank L W; Cann, Martin J

2015-10-09

Plant nucleotide-binding leucine-rich repeat (NLR) proteins enable cells to respond to pathogen attack. Several NLRs act in the nucleus; however, conserved nuclear targets that support their role in immunity are unknown. Previously, we noted a structural homology between the nucleotide-binding domain of NLRs and DNA replication origin-binding Cdc6/Orc1 proteins. Here we show that the NB-ARC (nucleotide-binding, Apaf-1, R-proteins, and CED-4) domain of the Rx1 NLR of potato binds nucleic acids. Rx1 induces ATP-dependent bending and melting of DNA in vitro, dependent upon a functional P-loop. In situ full-length Rx1 binds nuclear DNA following activation by its cognate pathogen-derived effector protein, the coat protein of potato virus X. In line with its obligatory nucleocytoplasmic distribution, DNA binding was only observed when Rx1 was allowed to freely translocate between both compartments and was activated in the cytoplasm. Immune activation induced by an unrelated NLR-effector pair did not trigger an Rx1-DNA interaction. DNA binding is therefore not merely a consequence of immune activation. These data establish a role for DNA distortion in Rx1 immune signaling and define DNA as a molecular target of an activated NLR. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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

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D. Pagliari

2015-01-01

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

Ets transcription factor GABP controls T cell homeostasis and immunity.

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Luo, Chong T; Osmanbeyoglu, Hatice U; Do, Mytrang H; Bivona, Michael R; Toure, Ahmed; Kang, Davina; Xie, Yuchen; Leslie, Christina S; Li, Ming O

2017-10-20

Peripheral T cells are maintained in the absence of vigorous stimuli, and respond to antigenic stimulation by initiating cell cycle progression and functional differentiation. Here we show that depletion of the Ets family transcription factor GA-binding protein (GABP) in T cells impairs T-cell homeostasis. In addition, GABP is critically required for antigen-stimulated T-cell responses in vitro and in vivo. Transcriptome and genome-wide GABP-binding site analyses identify GABP direct targets encoding proteins involved in cellular redox balance and DNA replication, including the Mcm replicative helicases. These findings show that GABP has a nonredundant role in the control of T-cell homeostasis and immunity.

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

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...

Induced Genome-Wide Binding of Three Arabidopsis WRKY Transcription Factors during Early MAMP-Triggered Immunity.

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Birkenbihl, Rainer P; Kracher, Barbara; Somssich, Imre E

2017-01-01

During microbial-associated molecular pattern-triggered immunity (MTI), molecules derived from microbes are perceived by cell surface receptors and upon signaling to the nucleus initiate a massive transcriptional reprogramming critical to mount an appropriate host defense response. WRKY transcription factors play an important role in regulating these transcriptional processes. Here, we determined on a genome-wide scale the flg22-induced in vivo DNA binding dynamics of three of the most prominent WRKY factors, WRKY18, WRKY40, and WRKY33. The three WRKY factors each bound to more than 1000 gene loci predominantly at W-box elements, the known WRKY binding motif. Binding occurred mainly in the 500-bp promoter regions of these genes. Many of the targeted genes are involved in signal perception and transduction not only during MTI but also upon damage-associated molecular pattern-triggered immunity, providing a mechanistic link between these functionally interconnected basal defense pathways. Among the additional targets were genes involved in the production of indolic secondary metabolites and in modulating distinct plant hormone pathways. Importantly, among the targeted genes were numerous transcription factors, encoding predominantly ethylene response factors, active during early MTI, and WRKY factors, supporting the previously hypothesized existence of a WRKY subregulatory network. Transcriptional analysis revealed that WRKY18 and WRKY40 function redundantly as negative regulators of flg22-induced genes often to prevent exaggerated defense responses. © 2016 American Society of Plant Biologists. All rights reserved.

Pseudomonas syringae evades host immunity by degrading flagellin monomers with alkaline protease AprA.

Science.gov (United States)

Pel, Michiel J C; van Dijken, Anja J H; Bardoel, Bart W; Seidl, Michael F; van der Ent, Sjoerd; van Strijp, Jos A G; Pieterse, Corné M J

2014-07-01

Bacterial flagellin molecules are strong inducers of innate immune responses in both mammals and plants. The opportunistic pathogen Pseudomonas aeruginosa secretes an alkaline protease called AprA that degrades flagellin monomers. Here, we show that AprA is widespread among a wide variety of bacterial species. In addition, we investigated the role of AprA in virulence of the bacterial plant pathogen P. syringae pv. tomato DC3000. The AprA-deficient DC3000 ΔaprA knockout mutant was significantly less virulent on both tomato and Arabidopsis thaliana. Moreover, infiltration of A. thaliana Col-0 leaves with DC3000 ΔaprA evoked a significantly higher level of expression of the defense-related genes FRK1 and PR-1 than did wild-type DC3000. In the flagellin receptor mutant fls2, pathogen virulence and defense-related gene activation did not differ between DC3000 and DC3000 ΔaprA. Together, these results suggest that AprA of DC3000 is important for evasion of recognition by the FLS2 receptor, allowing wild-type DC3000 to be more virulent on its host plant than AprA-deficient DC3000 ΔaprA. To provide further evidence for the role of DC3000 AprA in host immune evasion, we overexpressed the AprA inhibitory peptide AprI of DC3000 in A. thaliana to counteract the immune evasive capacity of DC3000 AprA. Ectopic expression of aprI in A. thaliana resulted in an enhanced level of resistance against wild-type DC3000, while the already elevated level of resistance against DC3000 ΔaprA remained unchanged. Together, these results indicate that evasion of host immunity by the alkaline protease AprA is important for full virulence of strain DC3000 and likely acts by preventing flagellin monomers from being recognized by its cognate immune receptor.

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

African Journals Online (AJOL)

Globally, immunization has been considered as one of the effective methods of reducing child morbidity and mortality rate. In spite of the increasing immunization coverage worldwide, Kaduna state in Nigeria has remained one of the areas with high mortality rate as a result of vaccine preventable diseases. Research ...

Drosophila imaginal disc growth factor 2 is a trophic factor involved in energy balance, detoxification, and innate immunity

Czech Academy of Sciences Publication Activity Database

Brož, Václav; Kučerová, Lucie; Rouhová, L.; Fleischmannová, Jana; Strnad, Hynek; Bryant, P. J.; Žurovec, Michal

2017-01-01

Roč. 7, FEB 23 (2017), č. článku 43273. ISSN 2045-2322 R&D Projects: GA ČR GA14-27816S; GA ČR GA14-07172S Institutional support: RVO:60077344 ; RVO:68378050 Keywords : Drosophila * innate immunity * IDGF2 Subject RIV: CE - Biochemistry; CE - Biochemistry (UMG-J) OBOR OECD: Biochemistry and molecular biology; Biochemistry and molecular biology (UMG-J) Impact factor: 4.259, year: 2016 http://www.nature.com/articles/srep43273

District-level variations in childhood immunizations in India: The role of socio-economic factors and health infrastructure.

Science.gov (United States)

Rammohan, Anu; Awofeso, Niyi

2015-11-01

Routine childhood immunizations against measles and DPT are part of the World Health Organization's (WHO) Expanded Program on Immunization (EPI) set up in 1974, with the aim of reducing childhood morbidity and mortality. Despite this, immunization rates are sub-optimal in developing countries such as India, with wide heterogeneity observed across districts and socio-economic characteristics. The aim of this paper is to examine district-level variations in the propensity to vaccinate a child in India for measles and DPT3, and analyse the extent to which these immunizations are given age-inappropriately, either prematurely or delayed. The present study uses data from the Indian District Level Household Survey (DLHS-3) collected in 2008, and the final sample contains detailed information on 42157 children aged between 12 and 60 months, across 549 Indian districts for whom we have complete information on immunization history. Our empirical study analyses: (i) the district-level average immunization rates for measles and DPT3, and (ii) the extent to which these immunizations have been given age-appropriately. A key contribution of this paper is that we link the household-level data at the district level to data on availability and proximity to health infrastructure and district-level socio-economic factors. Our results show that after controlling for an array of socio-economic characteristics, across all our models, the district's income per capita is a strong predictor of better immunization outcomes for children. Mother's education level at the district-level has a statistically significant and positive influence on immunization outcomes across all our models. Copyright © 2015 Elsevier Ltd. All rights reserved.

Some immune reactions of the personnel, subjected to combined effect of ionizing radiation and non-radiation factors

International Nuclear Information System (INIS)

Shubin, V.M.; Litver, B.Ya.; Zykova, I.A.

1978-01-01

Some factors of nonspecific bodily protection (bactericidal capacity, complement, lysozyme, beta lysins of blood serum) are analyzed in gamma defectoscopists and in workers exposed to occupational factors of nonradiation nature. A number of alterations in immunity indices in persons exposed to combined radiation and nonradiation factors (stimulation of beta lysins, increased levels of antitissue antibodies, etc.) had has been revealed. These alterations appear to have resulted from the potentiation of the effects from ionizing radiation and nonradiation nature factors

Mucosal immunization in macaques upregulates the innate APOBEC 3G anti-viral factor in CD4(+) memory T cells.

Science.gov (United States)

Wang, Yufei; Bergmeier, Lesley A; Stebbings, Richard; Seidl, Thomas; Whittall, Trevor; Singh, Mahavir; Berry, Neil; Almond, Neil; Lehner, Thomas

2009-02-05

APOBEC3G is an innate intracellular anti-viral factor which deaminates retroviral cytidine to uridine. In vivo studies of APOBEC3G (A3G) were carried out in rhesus macaques, following mucosal immunization with SIV antigens and CCR5 peptides, linked to the 70kDa heat shock protein. A progressive increase in A3G mRNA was elicited in PBMC after each immunization (p<0.0002 to p< or =0.02), which was maintained for at least 17 weeks. Analysis of memory T cells showed a significant increase in A3G mRNA and protein in CD4(+)CCR5(+) memory T cells in circulating (p=0.0001), splenic (p=0.0001), iliac lymph nodes (p=0.002) and rectal (p=0.01) cells of the immunized compared with unimmunized macaques. Mucosal challenge with SIVmac 251 showed a significant increase in A3G mRNA in the CD4(+)CCR5(+) circulating cells (p<0.01) and the draining iliac lymph node cells (p<0.05) in the immunized uninfected macaques, consistent with a protective effect exerted by A3G. The results suggest that mucosal immunization in a non-human primate can induce features of a memory response to an innate anti-viral factor in CCR5(+)CD4(+) memory and CD4(+)CD95(+)CCR7(-) effector memory T cells.

Th2-related immune responses by the Brucella abortus cellular antigens, malate dehydrogenase, elongation factor, and arginase.

Science.gov (United States)

Im, Young Bin; Shim, Soojin; Park, Woo Bin; Kim, Suk; Yoo, Han Sang

2017-09-01

Brucellosis is an important zoonotic disease caused by Brucella species. The disease is difficult to control due to the intracellular survival of the bacterium and the lack of precise understanding of pathogenesis. Despite of continuous researches on the pathogenesis of Brucella spp. infection, there is still question on the pathogenesis, especially earlier immune response in the bacterial infection. Malate dehydrogenase (MDH), elongation factor (Tsf), and arginase (RocF), which showed serological reactivity, were purified after gene cloning, and their immune modulating activities were then analyzed in a murine model. Cytokine production profiles were investigated by stimulating RAW 264.7 cells and naïve splenocytes with the three recombinant proteins. Also, immune responses were analyzed by ELISA and an ELIspot assay after immunizing mice with the three proteins. Only TNF-α was produced in stimulated RAW 264.7 cells, whereas Th1-related cytokines, IFN-γ and IL-2, were induced in naïve splenocytes. In contrast, Th2-type immune response was more strongly induced in antigen-secreting cells in the splenocytes obtained 28 days after immunizing mice with the three proteins, as were IgM and IgG. The induction of Th2-related antibody, IgG1, was higher than the Th1-related antibody, IgG2a, in immunized mice. These results suggest that the three proteins strongly induce Th2-type immune response in vivo, even though Th1-related cytokines were produced in vitro. Copyright © 2017 Elsevier Ltd. All rights reserved.

Immune-Modulating Perspectives for Low Frequency Electromagnetic Fields in Innate Immunity

Directory of Open Access Journals (Sweden)

Maria Manuela Rosado

2018-03-01

Full Text Available In recent years, the effects of electromagnetic fields (EMFs on the immune system have received a considerable interest, not only to investigate possible negative health impact but also to explore the possibility to favorably modulate immune responses. To generate beneficial responses, the immune system should eradicate pathogens while “respecting” the organism and tolerating irrelevant antigens. According to the current view, damage-associated molecules released by infected or injured cells, or secreted by innate immune cells generate danger signals activating an immune response. These signals are also relevant to the subsequent activation of homeostatic mechanisms that control the immune response in pro- or anti-inflammatory reactions, a feature that allows modulation by therapeutic treatments. In the present review, we describe and discuss the effects of extremely low frequency (ELF-EMF and pulsed EMF on cell signals and factors relevant to the activation of danger signals and innate immunity cells. By discussing the EMF modulating effects on cell functions, we envisage the use of EMF as a therapeutic agent to regulate immune responses associated with wound healing.

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.

The Verticillium-specific protein VdSCP7 localizes to the plant nucleus and modulates immunity to fungal infections.

Science.gov (United States)

Zhang, Lisha; Ni, Hao; Du, Xuan; Wang, Sheng; Ma, Xiao-Wei; Nürnberger, Thorsten; Guo, Hui-Shan; Hua, Chenlei

2017-07-01

Fungal pathogens secrete effector proteins to suppress plant basal defense for successful colonization. Resistant plants, however, can recognize effectors by cognate R proteins to induce effector-triggered immunity (ETI). By analyzing secretomes of the vascular fungal pathogen Verticillium dahliae, we identified a novel secreted protein VdSCP7 that targets the plant nucleus. The green fluorescent protein (GFP)-tagged VdSCP7 gene with either a mutated nuclear localization signal motif or with additional nuclear export signal was transiently expressed in Nicotiana benthamiana, and investigated for induction of plant immunity. The role of VdSCP7 in V. dahliae pathogenicity was characterized by gene knockout and complementation, and GFP labeling. Expression of the VdSCP7 gene in N. benthamiana activated both salicylic acid and jasmonate signaling, and altered the plant's susceptibility to the pathogens Botrytis cinerea and Phytophthora capsici. The immune response activated by VdSCP7 was highly dependent on its initial extracellular secretion and subsequent nuclear localization in plants. Knockout of the VdSCP7 gene significantly enhanced V. dahliae aggressiveness on cotton. GFP-labeled VdSCP7 is secreted by V. dahliae and accumulates in the plant nucleus. We conclude that VdSCP7 is a novel effector protein that targets the host nucleus to modulate plant immunity, and suggest that plants can recognize VdSCP7 to activate ETI during fungal infection. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Macrophage-derived insulin-like growth factor-1 affects influenza vaccine efficacy through the regulation of immune cell homeostasis.

Science.gov (United States)

Yoon, Il-Sub; Park, Hyelim; Kwak, Hye-Won; Woo Jung, Yong; Nam, Jae-Hwan

2017-08-24

The level of antibody production induced by a vaccine involves a variety of host factors. One of these, insulin-like growth factor-1 (IGF-1), plays an important role in lymphocyte maturation and antibody expression. Here, we investigated the role of macrophage-derived IGF-1 in the induction of influenza vaccine-specific antibodies using macrophage-derived IGF-1 gene knockout (MIKO) mice. The titers of vaccine-specific total immunoglobulin G (IgG) and IgG1 after immunization were about two- to fourfold lower in MIKO mice than in WT mice. Moreover, MIKO mice showed a relatively weak booster effect of repeated immunization. In contrast, antigen-nonspecific total IgG was about threefold higher in MIKO mice than in WT mice. After viral challenge, the viral titer and the pathological damage in lungs of MIKO mice were higher than those in WT mice despite vaccination. Interestingly, the proportions of proinflammatory immune cells including M1 macrophages, Th1 and Th17 cells was higher in unvaccinated MIKO mice than in unvaccinated WT mice. This suggests that nonspecific activation of immune cells may paradoxically impair the response to the vaccine. In addition, although the proportions of T follicular helper (Tfh) cells and GL-7 + germinal center (GC) B cells were higher in MIKO mice than in WT mice, the population of CD138 + B220 + antibody-secreting plasmablasts was lower in MIKO mice, which may be a cause of the low influenza-specific antibody titer in MIKO mice. Taken together, these results suggest that macrophage-derived IGF-1 might play an important role in the vaccine-triggered immune response by regulating immune cell homeostasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis.

Science.gov (United States)

Sun, Honghong; Gong, Shunyou; Carmody, Ruaidhri J; Hilliard, Anja; Li, Li; Sun, Jing; Kong, Li; Xu, Lingyun; Hilliard, Brendan; Hu, Shimin; Shen, Hao; Yang, Xiaolu; Chen, Youhai H

2008-05-02

Immune homeostasis is essential for the normal functioning of the immune system, and its breakdown leads to fatal inflammatory diseases. We report here the identification of a member of the tumor necrosis factor-alpha-induced protein-8 (TNFAIP8) family, designated TIPE2, that is required for maintaining immune homeostasis. TIPE2 is preferentially expressed in lymphoid tissues, and its deletion in mice leads to multiorgan inflammation, splenomegaly, and premature death. TIPE2-deficient animals are hypersensitive to septic shock, and TIPE2-deficient cells are hyper-responsive to Toll-like receptor (TLR) and T cell receptor (TCR) activation. Importantly, TIPE2 binds to caspase-8 and inhibits activating protein-1 and nuclear factor-kappaB activation while promoting Fas-induced apoptosis. Inhibiting caspase-8 significantly blocks the hyper-responsiveness of TIPE2-deficient cells. These results establish that TIPE2 is an essential negative regulator of TLR and TCR function, and its selective expression in the immune system prevents hyperresponsiveness and maintains immune homeostasis.

Enhancing immune responses to inactivated porcine parvovirus oil emulsion vaccine by co-inoculating porcine transfer factor in mice.

Science.gov (United States)

Wang, Rui-ning; Wang, Ya-bin; Geng, Jing-wei; Guo, Dong-hui; Liu, Fang; Chen, Hong-ying; Zhang, Hong-ying; Cui, Bao-an; Wei, Zhan-yong

2012-07-27

Inactivated porcine parvovirus (PPV) vaccines are available commercially and widely used in the breeding herds. However, inactivated PPV vaccines have deficiencies in induction of specific cellular immune response. Transfer factor (TF) is a material that obtained from the leukocytes, and is a novel immune-stimulatory reagent that as a modulator of the immune system. In this study, the immunogenicity of PPV oil emulsion vaccine and the immuno-regulatory activities of TF were investigated. The inactivated PPV oil emulsion vaccines with or without TF were inoculated into BALB/c mice by subcutaneous injection. Then humoral and cellular immune responses were evaluated by indirect enzyme-linked immunosorbent assays (ELISA), fluorescence-activated cell sorter analyses (FACS). The results showed that the PPV specific immune responses could be evoked in mice by inoculating with PPV oil emulsion vaccine alone or by co-inoculation with TF. The cellular immune response levels in the co-inoculation groups were higher than those groups receiving the PPV oil emulsion vaccine alone, with the phenomena of higher level of IFN-γ, a little IL-6 and a trace of IL-4 in serum, and a vigorous T-cell response. However, there was no significant difference in antibody titers between TF synergy inactivated vaccine and the inactivated vaccine group (P>0.05). In conclusion, these results suggest that TF possess better cellular immune-enhancing capability and would be exploited into an effective immune-adjuvant for inactivated vaccines. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

Directory of Open Access Journals (Sweden)

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

HPV-E7 Delivered by Engineered Exosomes Elicits a Protective CD8+ T Cell-Mediated Immune Response

Science.gov (United States)

Di Bonito, Paola; Ridolfi, Barbara; Columba-Cabezas, Sandra; Giovannelli, Andrea; Chiozzini, Chiara; Manfredi, Francesco; Anticoli, Simona; Arenaccio, Claudia; Federico, Maurizio

2015-01-01

We developed an innovative strategy to induce a cytotoxic T cell (CTL) immune response against protein antigens of choice. It relies on the production of exosomes, i.e., nanovesicles spontaneously released by all cell types. We engineered the upload of huge amounts of protein antigens upon fusion with an anchoring protein (i.e., HIV-1 Nefmut), which is an inactive protein incorporating in exosomes at high levels also when fused with foreign proteins. We compared the immunogenicity of engineered exosomes uploading human papillomavirus (HPV)-E7 with that of lentiviral virus-like particles (VLPs) incorporating equivalent amounts of the same antigen. These exosomes, whose limiting membrane was decorated with VSV-G, i.e., an envelope protein inducing pH-dependent endosomal fusion, proved to be as immunogenic as the cognate VLPs. It is noteworthy that the immunogenicity of the engineered exosomes remained unaltered in the absence of VSV-G. Most important, we provide evidence that the inoculation in mouse of exosomes uploading HPV-E7 induces production of anti-HPV E7 CTLs, blocks the growth of syngeneic tumor cells inoculated after immunization, and controls the development of tumor cells inoculated before the exosome challenge. These results represent the proof-of-concept about both feasibility and efficacy of the Nefmut-based exosome platform for the induction of CD8+ T cell immunity. PMID:25760140

HPV-E7 Delivered by Engineered Exosomes Elicits a Protective CD8+ T Cell-Mediated Immune Response

Directory of Open Access Journals (Sweden)

Paola Di Bonito

2015-03-01

Full Text Available We developed an innovative strategy to induce a cytotoxic T cell (CTL immune response against protein antigens of choice. It relies on the production of exosomes, i.e., nanovesicles spontaneously released by all cell types. We engineered the upload of huge amounts of protein antigens upon fusion with an anchoring protein (i.e., HIV-1 Nefmut, which is an inactive protein incorporating in exosomes at high levels also when fused with foreign proteins. We compared the immunogenicity of engineered exosomes uploading human papillomavirus (HPV-E7 with that of lentiviral virus-like particles (VLPs incorporating equivalent amounts of the same antigen. These exosomes, whose limiting membrane was decorated with VSV-G, i.e., an envelope protein inducing pH-dependent endosomal fusion, proved to be as immunogenic as the cognate VLPs. It is noteworthy that the immunogenicity of the engineered exosomes remained unaltered in the absence of VSV-G. Most important, we provide evidence that the inoculation in mouse of exosomes uploading HPV-E7 induces production of anti-HPV E7 CTLs, blocks the growth of syngeneic tumor cells inoculated after immunization, and controls the development of tumor cells inoculated before the exosome challenge. These results represent the proof-of-concept about both feasibility and efficacy of the Nefmut-based exosome platform for the induction of CD8+ T cell immunity.

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

Science.gov (United States)

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

A Plant Immune Receptor Detects Pathogen Effectors that Target WRKY Transcription Factors.

Science.gov (United States)

Sarris, Panagiotis F; Duxbury, Zane; Huh, Sung Un; Ma, Yan; Segonzac, Cécile; Sklenar, Jan; Derbyshire, Paul; Cevik, Volkan; Rallapalli, Ghanasyam; Saucet, Simon B; Wirthmueller, Lennart; Menke, Frank L H; Sohn, Kee Hoon; Jones, Jonathan D G

2015-05-21

Defense against pathogens in multicellular eukaryotes depends on intracellular immune receptors, yet surveillance by these receptors is poorly understood. Several plant nucleotide-binding, leucine-rich repeat (NB-LRR) immune receptors carry fusions with other protein domains. The Arabidopsis RRS1-R NB-LRR protein carries a C-terminal WRKY DNA binding domain and forms a receptor complex with RPS4, another NB-LRR protein. This complex detects the bacterial effectors AvrRps4 or PopP2 and then activates defense. Both bacterial proteins interact with the RRS1 WRKY domain, and PopP2 acetylates lysines to block DNA binding. PopP2 and AvrRps4 interact with other WRKY domain-containing proteins, suggesting these effectors interfere with WRKY transcription factor-dependent defense, and RPS4/RRS1 has integrated a "decoy" domain that enables detection of effectors that target WRKY proteins. We propose that NB-LRR receptor pairs, one member of which carries an additional protein domain, enable perception of pathogen effectors whose function is to target that domain. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

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.

IL-4Rα-associated antigen processing by B cells promotes immunity in Nippostrongylus brasiliensis infection.

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William G C Horsnell

2013-10-01

Full Text Available In this study, B cell function in protective T(H2 immunity against N. brasiliensis infection was investigated. Protection against secondary infection depended on IL-4Rα and IL-13; but not IL-4. Protection did not associate with parasite specific antibody responses. Re-infection of B cell-specific IL-4Rα⁻/⁻ mice resulted in increased worm burdens compared to control mice, despite their equivalent capacity to control primary infection. Impaired protection correlated with reduced lymphocyte IL-13 production and B cell MHC class II and CD86 surface expression. Adoptive transfer of in vivo N. brasiliensis primed IL-4Rα expressing B cells into naïve BALB/c mice, but not IL-4Rα or IL-13 deficient B cells, conferred protection against primary N. brasiliensis infection. This protection required MHC class II compatibility on B cells suggesting cognate interactions by B cells with CD4⁺ T cells were important to co-ordinate immunity. Furthermore, the rapid nature of these protective effects by B cells suggested non-BCR mediated mechanisms, such as via Toll Like Receptors, was involved, and this was supported by transfer experiments using antigen pulsed Myd88⁻/⁻ B cells. These data suggest TLR dependent antigen processing by IL-4Rα-responsive B cells producing IL-13 contribute significantly to CD4⁺ T cell-mediated protective immunity against N. brasiliensis infection.

[Stress and auto-immunity].

Science.gov (United States)

Delévaux, I; Chamoux, A; Aumaître, O

2013-08-01

The etiology of auto-immune disorders is multifactorial. Stress is probably a participating factor. Indeed, a high proportion of patients with auto-immune diseases report uncommon stress before disease onset or disease flare. The biological consequences of stress are increasingly well understood. Glucocorticoids and catecholamines released by hypothalamic-pituitary-adrenal axis during stress will alter the balance Th1/Th2 and the balance Th17/Treg. Stress impairs cellular immunity, decreases immune tolerance and stimulates humoral immunity exposing individuals to autoimmune disease among others. The treatment for autoimmune disease should include stress management. Copyright © 2012 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Cognate CD4 T-cell licensing of dendritic cells heralds anti-CMV CD8 T-cell immunity after human allogeneic umbilical cord blood transplantation

NARCIS (Netherlands)

Flinsenberg, T W H; Spel, Lotte; Jansen, M; Koning, D; de Haar, C; Plantinga, M; Scholman, R; van Loenen, M M; Nierkens, S; Boon, L; van Baarle, D; Heemskerk, M H M; Boelens, J J; Boes, M

2014-01-01

Reactivation of human cytomegalovirus (CMV) is hazardous to patients undergoing allogeneic cord-blood transplantation (CBT), lowering survival rates by approximately 25%. While antiviral treatment ameliorates viremia, complete viral control requires CD8(+) T-cell-driven immunity. Mouse studies

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.

Role of maternally derived immunity in fish.

Science.gov (United States)

Swain, P; Nayak, S K

2009-08-01

Maternal immunity is of paramount importance for protection of young ones at early stage of life since the immune factors of an immunocompetent female are transferred transplacentally or through colostrum, milk or yolk to an immunologically naive neonate. Both innate and adaptive type of immunity are transferred of from mother to offspring in fishes. These factors include immunoglobulin (Ig)/antibody, complement factors, lysozymes, protease inhibitors like alpha macroglobulin, different types of lectins and serine proteases like molecules. Among different types of Ig viz. IgM, IgD, IgT/IgZ and IgM-IgZ chimera types, IgM is present in most of the teleostean fishes. In teleosts, IgM either as a reduced/breakdown product or monomeric form is usually transferred to the offsprings. The maternally derived IgM usually persists for a limited duration, exhausts within the completion of yolk absorption process, and completely disappears thereafter during larval stages. Maternal transfer of immunity which provides defense to embryo and larvae depends upon the health as well as the immune status of brood fish. The overall health status of brood fish can affect breeding performances, quality seed production and protection of offsprings. However, factors such as age, maturation, reproductive behaviour and nutrition (micro and macro-nutrients) may affect the immunity in brood fishes. Besides these, seasonal changes such as photoperiods, temperature, adverse environmental conditions, and stress conditions like handling, crowding, and water pollution/contamination can also affect the immunity of brood fishes. The maintenance of the brood stock immunity at high level during vitellogenesis and oogenesis, is utmost important for reducing mortalities at larval/post larval stages through maximum/optimum transfer of maternal immunity. Brood stock immunization prior to breeding as well as selective breeding among the disease resistant families might be the ideal criteria for producing

Innate Immunity and Breast Milk.

Science.gov (United States)

Cacho, Nicole Theresa; Lawrence, Robert M

2017-01-01

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

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 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 antigens have a greater magnitude compared to ESAT-6

The tomato Fni3 lysine-63-specific ubiquitin-conjugating enzyme and suv ubiquitin E2 variant positively regulate plant immunity.

Science.gov (United States)

Mural, Ravi V; Liu, Yao; Rosebrock, Tracy R; Brady, Jennifer J; Hamera, Sadia; Connor, Richard A; Martin, Gregory B; Zeng, Lirong

2013-09-01

The activation of an immune response in tomato (Solanum lycopersicum) against Pseudomonas syringae relies on the recognition of E3 ligase-deficient forms of AvrPtoB by the host protein kinase, Fen. To investigate the mechanisms by which Fen-mediated immunity is regulated, we characterize in this study a Fen-interacting protein, Fni3, and its cofactor, S. lycoperiscum Uev (Suv). Fni3 encodes a homolog of the Ubc13-type ubiquitin-conjugating enzyme that catalyzes exclusively Lys-63-linked ubiquitination, whereas Suv is a ubiquitin-conjugating enzyme variant. The C-terminal region of Fen was necessary for interaction with Fni3, and this interaction was required for cell death triggered by overexpression of Fen in Nicotiana benthamiana leaves. Fni3 was shown to be an active E2 enzyme, but Suv displayed no ubiquitin-conjugating activity; Fni3 and Suv together directed Lys-63-linked ubiquitination. Decreased expression of Fni3, another tomato Ubc13 homolog, Sl-Ubc13-2, or Suv in N. benthamiana leaves diminished cell death associated with Fen-mediated immunity and cell death elicited by several other resistance (R) proteins and their cognate effectors. We also discovered that coexpression of Fen and other R proteins/effectors with a Fni3 mutant that is compromised for ubiquitin-conjugating activity diminished the cell death. These results suggest that Fni3/Sl-Ubc13-2 and Suv regulate the immune response mediated by Fen and other R proteins through Lys-63-linked ubiquitination.

Inhibition of Allograft Inflammatory Factor-1 in Dendritic Cells Restrains CD4+ T Cell Effector Responses and Induces CD25+Foxp3+ T Regulatory Subsets

Directory of Open Access Journals (Sweden)

Diana M. Elizondo

2017-11-01

Full Text Available Allograft inflammatory factor-1 (AIF1 is a cytoplasmic scaffold protein shown to influence immune responses in macrophages and microglial cells. The protein contains Ca2+ binding EF-hand and PDZ interaction domains important for mediating intracellular signaling complexes. This study now reports that AIF1 is expressed in CD11c+ dendritic cells (DC and silencing of expression restrains induction of antigen-specific CD4+ T cell effector responses. AIF1 knockdown in murine DC resulted in impaired T cell proliferation and skewed polarization away from T helper type 1 and 17 fates. In turn, there was a parallel expansion of IL-10-producing and CD25+Foxp3+ T regulatory subsets. These studies are the first to demonstrate that AIF1 expression in DC serves as a potent governor of cognate T cell responses and presents a novel target for engineering tolerogenic DC-based immunotherapies.

Regulator-dependent mechanisms of C3b processing by factor i allow differentiation of immune responses

NARCIS (Netherlands)

Xue, Xiaoguang|info:eu-repo/dai/nl/413576841; Wu, Jin|info:eu-repo/dai/nl/304829552; Ricklin, Daniel; Forneris, Federico|info:eu-repo/dai/nl/341358622; Di Crescenzio, Patrizia; Schmidt, Christoph Q.; Granneman, Joke|info:eu-repo/dai/nl/304839396; Sharp, Thomas H; Lambris, John D; Gros, Piet|info:eu-repo/dai/nl/075243016

2017-01-01

The complement system labels microbes and host debris for clearance. Degradation of surface-bound C3b is pivotal to direct immune responses and protect host cells. How the serine protease factor I (FI), assisted by regulators, cleaves either two or three distant peptide bonds in the CUB domain of

Foetal immune programming: hormones, cytokines, microbes and regulatory T cells.

Science.gov (United States)

Hsu, Peter; Nanan, Ralph

2014-10-01

In addition to genetic factors, environmental cues play important roles in shaping the immune system. The first environment that the developing foetal immune system encounters is the uterus. Although physically the mother and the foetus are separated by the placental membranes, various factors such as hormones and cytokines may provide "environmental cues" to the foetal immune system. Additionally, increasing evidence suggests that prenatal maternal environmental factors, particularly microbial exposure, might significantly influence the foetal immune system, affecting long-term outcomes, a concept termed foetal immune programming. Here we discuss the potential mediators of foetal immune programming, focusing on the role of pregnancy-related hormones, cytokines and regulatory T cells, which play a critical role in immune tolerance. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Identification, structure, and function of a novel type VI secretion peptidoglycan glycoside hydrolase effector-immunity pair.

Science.gov (United States)

Whitney, John C; Chou, Seemay; Russell, Alistair B; Biboy, Jacob; Gardiner, Taylor E; Ferrin, Michael A; Brittnacher, Mitchell; Vollmer, Waldemar; Mougous, Joseph D

2013-09-13

Bacteria employ type VI secretion systems (T6SSs) to facilitate interactions with prokaryotic and eukaryotic cells. Despite the widespread identification of T6SSs among Gram-negative bacteria, the number of experimentally validated substrate effector proteins mediating these interactions remains small. Here, employing an informatics approach, we define novel families of T6S peptidoglycan glycoside hydrolase effectors. Consistent with the known intercellular self-intoxication exhibited by the T6S pathway, we observe that each effector gene is located adjacent to a hypothetical open reading frame encoding a putative periplasmically localized immunity determinant. To validate our sequence-based approach, we functionally investigate a representative family member from the soil-dwelling bacterium Pseudomonas protegens. We demonstrate that this protein is secreted in a T6SS-dependent manner and that it confers a fitness advantage in growth competition assays with Pseudomonas putida. In addition, we determined the 1.4 Å x-ray crystal structure of this effector in complex with its cognate immunity protein. The structure reveals the effector shares highest overall structural similarity to a glycoside hydrolase family associated with peptidoglycan N-acetylglucosaminidase activity, suggesting that T6S peptidoglycan glycoside hydrolase effector families may comprise significant enzymatic diversity. Our structural analyses also demonstrate that self-intoxication is prevented by the immunity protein through direct occlusion of the effector active site. This work significantly expands our current understanding of T6S effector diversity.

Identification, Structure, and Function of a Novel Type VI Secretion Peptidoglycan Glycoside Hydrolase Effector-Immunity Pair*

Science.gov (United States)

Whitney, John C.; Chou, Seemay; Russell, Alistair B.; Biboy, Jacob; Gardiner, Taylor E.; Ferrin, Michael A.; Brittnacher, Mitchell; Vollmer, Waldemar; Mougous, Joseph D.

2013-01-01

Bacteria employ type VI secretion systems (T6SSs) to facilitate interactions with prokaryotic and eukaryotic cells. Despite the widespread identification of T6SSs among Gram-negative bacteria, the number of experimentally validated substrate effector proteins mediating these interactions remains small. Here, employing an informatics approach, we define novel families of T6S peptidoglycan glycoside hydrolase effectors. Consistent with the known intercellular self-intoxication exhibited by the T6S pathway, we observe that each effector gene is located adjacent to a hypothetical open reading frame encoding a putative periplasmically localized immunity determinant. To validate our sequence-based approach, we functionally investigate a representative family member from the soil-dwelling bacterium Pseudomonas protegens. We demonstrate that this protein is secreted in a T6SS-dependent manner and that it confers a fitness advantage in growth competition assays with Pseudomonas putida. In addition, we determined the 1.4 Å x-ray crystal structure of this effector in complex with its cognate immunity protein. The structure reveals the effector shares highest overall structural similarity to a glycoside hydrolase family associated with peptidoglycan N-acetylglucosaminidase activity, suggesting that T6S peptidoglycan glycoside hydrolase effector families may comprise significant enzymatic diversity. Our structural analyses also demonstrate that self-intoxication is prevented by the immunity protein through direct occlusion of the effector active site. This work significantly expands our current understanding of T6S effector diversity. PMID:23878199

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

2014-01-01

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. PMID:24398686

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.

Immunity and skin cancer

International Nuclear Information System (INIS)

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

1981-01-01

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

The role of TLR2 and bacterial lipoprotein in enhancing airway inflammation and immunity

Directory of Open Access Journals (Sweden)

Amit A Lugade

2011-04-01

Full Text Available Non-typeable Haemophilus influenzae (NTHI colonizes the lower respiratory tract of patients with chronic obstructive pulmonary disease (COPD and also causes exacerbations of the disease. The 16-kDa lipoprotein P6 has been widely studied as a potential vaccine antigen due to its highly conserved expression amongst NTHI strains. Although P6 is known to induce potent inflammatory responses, its role in the pathogenesis of NTHI infection in vivo has not been examined. Additionally, the presence of an amino-terminal lipid motif on P6 serves to activate host TLR2 signaling. The role of host Toll-like receptor 2 (TLR2 and NTHI expression of the lipoprotein P6 on the induction of airway inflammation and generation of adaptive immune responses following chronic NTHI stimulation was evaluated with TLR2-deficient mice and a P6-deficient NTHI strain. Absence of either host TLR2 or bacterial P6 resulted in diminished levels of immune cell infiltration within lungs of mice exposed to NTHI. Pro-inflammatory cytokine secretion was also reduced in lungs that did not express TLR2 or were exposed to NTHI devoid of P6. Induction of specific antibodies to P6 was severely limited in TLR2-deficient mice. Although mice exposed to the P6-deficient NTHI strain were capable of generating antibodies to other surface antigens of NTHI, these levels were lower compared to those observed in mice exposed to P6-expressing NTHI. Therefore, cognate interaction between host TLR2 and bacterial P6 serves to enhance lung inflammation and elicit robust adaptive immune responses during NTHI exposure. Strategies to limit NTHI inflammation while simultaneously promoting robust immune responses may benefit from targeting the TLR2:P6 signaling axis.

HMGB1 and cord blood: its role as immuno-adjuvant factor in innate immunity.

Directory of Open Access Journals (Sweden)

Alessandra Ciucci

Full Text Available In newborn the innate immune system provides essential protection during primary infections before the generation of an appropriate adaptive immune response that is initially not fully operative. Innate immune response is evoked and perpetuated by molecules derived from microorganisms or by the damage/death of host cells. These are collectively known as damage-associated molecular-pattern (DAMP molecules. High-mobility group box 1 protein (HMGB1 or amphoterin, which previously was considered to be only a nuclear factor, has been recently identified as a DAMP molecule. When it is actively secreted by inflammatory cells or passively released from necrotic cells, HMGB1 mediates the response to infection, injury and inflammation, inducing dendritic cells maturation and T helper-1-cell responses. To characterize the role of HMGB1 in the innate and immature defense mechanisms in newborns, human cord blood (CB mononuclear cells, in comparison to adult peripheral blood (PB mononuclear cells, have been analyzed for its expression. By flow cytometry and western blot analysis, we observed that in CB and PB cells: i HMGB1 is expressed on cell surface membranes of myeloid dendritic cell precursors, mostly, and lymphocytes (gamma/delta and CD4(+ T cells to a lesser extent; ii different pro-inflammatory stimuli or molecules that mimic infection increased cell surface expression of HMGB1 as well as its secretion into extracellular environment; iii the treatment with synthetic molecules such as aminobisphosphonates (ABs, identified to be γδ T cell antigens, triggered up-regulation of HMGB1 expression on mononuclear cells, as well γδ T lymphocytes, inducing its secretion. The modulation of its secretion and the HMGB1-mediated migration of monocytes indicated HMGB1 as regulator of immune response in an immature system, like CB, through engagement of γδ T lymphocytes and myeloid dendritic cell precursors, essential components of innate immunity. In addition

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

HPV-E7 delivered by engineered exosomes elicits a protective CD8⁺ T cell-mediated immune response.

Science.gov (United States)

Di Bonito, Paola; Ridolfi, Barbara; Columba-Cabezas, Sandra; Giovannelli, Andrea; Chiozzini, Chiara; Manfredi, Francesco; Anticoli, Simona; Arenaccio, Claudia; Federico, Maurizio

2015-03-09

We developed an innovative strategy to induce a cytotoxic T cell (CTL) immune response against protein antigens of choice. It relies on the production of exosomes, i.e., nanovesicles spontaneously released by all cell types. We engineered the upload of huge amounts of protein antigens upon fusion with an anchoring protein (i.e., HIV-1 Nefmut), which is an inactive protein incorporating in exosomes at high levels also when fused with foreign proteins. We compared the immunogenicity of engineered exosomes uploading human papillomavirus (HPV)-E7 with that of lentiviral virus-like particles (VLPs) incorporating equivalent amounts of the same antigen. These exosomes, whose limiting membrane was decorated with VSV-G, i.e., an envelope protein inducing pH-dependent endosomal fusion, proved to be as immunogenic as the cognate VLPs. It is noteworthy that the immunogenicity of the engineered exosomes remained unaltered in the absence of VSV-G. Most important, we provide evidence that the inoculation in mouse of exosomes uploading HPV-E7 induces production of anti-HPV E7 CTLs, blocks the growth of syngeneic tumor cells inoculated after immunization, and controls the development of tumor cells inoculated before the exosome challenge. These results represent the proof-of-concept about both feasibility and efficacy of the Nefmut-based exosome platform for the induction of CD8+ T cell immunity.

Innate and intrinsic antiviral immunity in skin.

Science.gov (United States)

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

2014-09-01

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

Tribbles ortholog NIPI-3 and bZIP transcription factor CEBP-1 regulate a Caenorhabditis elegans intestinal immune surveillance pathway.

Science.gov (United States)

McEwan, Deborah L; Feinbaum, Rhonda L; Stroustrup, Nicholas; Haas, Wilhelm; Conery, Annie L; Anselmo, Anthony; Sadreyev, Ruslan; Ausubel, Frederick M

2016-12-07

Many pathogens secrete toxins that target key host processes resulting in the activation of immune pathways. The secreted Pseudomonas aeruginosa toxin Exotoxin A (ToxA) disrupts intestinal protein synthesis, which triggers the induction of a subset of P. aeruginosa-response genes in the nematode Caenorhabditis elegans. We show here that one ToxA-induced C. elegans gene, the Tribbles pseudokinase ortholog nipi-3, is essential for host survival following exposure to P. aeruginosa or ToxA. We find that NIPI-3 mediates the post-developmental expression of intestinal immune genes and proteins and primarily functions in parallel to known immune pathways, including p38 MAPK signaling. Through mutagenesis screening, we identify mutants of the bZIP C/EBP transcription factor cebp-1 that suppress the hypersusceptibility defects of nipi-3 mutants. NIPI-3 is a negative regulator of CEBP-1, which in turn negatively regulates protective immune mechanisms. This pathway represents a previously unknown innate immune signaling pathway in intestinal epithelial cells that is involved in the surveillance of cellular homeostasis. Because NIPI-3 and CEBP-1 are also essential for C. elegans development, NIPI-3 is analogous to other key innate immune signaling molecules such as the Toll receptors in Drosophila that have an independent role during development.

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 ...

Improved Insulin Sensitivity despite Increased Visceral Adiposity in Mice Deficient for the Immune Cell Transcription Factor T-bet

Science.gov (United States)

Stolarczyk, Emilie; Vong, Chi Teng; Perucha, Esperanza; Jackson, Ian; Cawthorne, Michael A.; Wargent, Edward T.; Powell, Nick; Canavan, James B.; Lord, Graham M.; Howard, Jane K.

2013-01-01

Summary Low-grade inflammation in fat is associated with insulin resistance, although the mechanisms are unclear. We report that mice deficient in the immune cell transcription factor T-bet have lower energy expenditure and increased visceral fat compared with wild-type mice, yet paradoxically are more insulin sensitive. This striking phenotype, present in young T-bet−/− mice, persisted with high-fat diet and increasing host age and was associated with altered immune cell numbers and cytokine secretion specifically in visceral adipose tissue. However, the favorable metabolic phenotype observed in T-bet-deficient hosts was lost in T-bet−/− mice also lacking adaptive immunity (T-bet−/−xRag2−/−), demonstrating that T-bet expression in the adaptive rather than the innate immune system impacts host glucose homeostasis. Indeed, adoptive transfer of T-bet-deficient, but not wild-type, CD4+ T cells to Rag2−/− mice improved insulin sensitivity. Our results reveal a role for T-bet in metabolic physiology and obesity-associated insulin resistance. PMID:23562076

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

Science.gov (United States)

Lehmann, Irina

2017-06-01

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

Cross activity of orthologous WRKY transcription factors in wheat and Arabidopsis

NARCIS (Netherlands)

Poietti, S.; Bertini, L.; Ent, S. van der; Leon Reyes, H.A.; Pieterse, C.M.J.; Tucci, M.; Caporale, C.; Caruso, C.

2011-01-01

WRKY proteins are transcription factors involved in many plant processes including plant responses to pathogens. Here, the cross activity of TaWRKY78 from the monocot wheat and AtWRKY20 from the dicot Arabidopsis on the cognate promoters of the orthologous PR4-type genes wPR4e and AtHEL of wheat and

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

Prognostic Factors for Immune Thrombocytopenia Outcome in Greek Children: A Retrospective Single-Centered Analysis

OpenAIRE

Makis, Alexandros; Gkoutsias, Athanasios; Palianopoulos, Theodoros; Pappa, Eleni; Papapetrou, Evangelia; Tsaousi, Christina; Hatzimichael, Eleftheria; Chaliasos, Nikolaos

2017-01-01

Immune thrombocytopenia (ITP) in children has a varied course and according to duration is distinguished as newly diagnosed (12) types. Several studies have evaluated the prognostic factors for the progression of the disease, but similar works have yet to be performed in Greece. We aimed to identify prognostic markers for the three forms of the disease in 57 Greek children during a 13-year period. Information regarding age, gender, preceding infection, bleeding type, duration of symptoms and ...

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....

Innate Immunity and Breast Milk

Directory of Open Access Journals (Sweden)

Nicole Theresa Cacho

2017-05-01

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

The intracellular immune receptor Rx1 regulates the DNA-binding activity of a Golden2-like transcription factor.

Science.gov (United States)

Townsend, Philip D; Dixon, Christopher H; Slootweg, Erik J; Sukarta, Octavina C A; Yang, Ally W H; Hughes, Timothy R; Sharples, Gary J; Pålsson, Lars-Olof; Takken, Frank L W; Goverse, Aska; Cann, Martin J

2018-03-02

Plant nucleotide-binding leucine-rich repeat (NLR) proteins enable the immune system to recognize and respond to pathogen attack. An early consequence of immune activation is transcriptional reprogramming, and some NLRs have been shown to act in the nucleus and interact with transcription factors. The Rx1 NLR protein of potato is further able to bind and distort double-stranded DNA. However, Rx1 host targets that support a role for Rx1 in transcriptional reprogramming at DNA are unknown. Here, we report a functional interaction between Rx1 and Nb Glk1, a Golden2-like transcription factor. Rx1 binds to Nb Glk1 in vitro and in planta. Nb Glk1 binds to known Golden2-like consensus DNA sequences. Rx1 reduces the binding affinity of Nb Glk1 for DNA in vitro. Nb Glk1 activates cellular responses to potato virus X, whereas Rx1 associates with Nb Glk1 and prevents its assembly on DNA in planta unless activated by PVX. This study provides new mechanistic insight into how an NLR can coordinate an immune signaling response at DNA following pathogen perceptions. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

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

Directory of Open Access Journals (Sweden)

Susu eDuan

2016-02-01

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

Sequence-specific high mobility group box factors recognize 10-12-base pair minor groove motifs

DEFF Research Database (Denmark)

van Beest, M; Dooijes, D; van De Wetering, M

2000-01-01

Sequence-specific high mobility group (HMG) box factors bind and bend DNA via interactions in the minor groove. Three-dimensional NMR analyses have provided the structural basis for this interaction. The cognate HMG domain DNA motif is generally believed to span 6-8 bases. However, alignment...

The role of epidermal cytokines in the generation of cutaneous immune reactions and ultraviolet radiation-induced immune suppression

International Nuclear Information System (INIS)

Ullrich, S.E.

1995-01-01

The immune suppression generated by UV exposure is a major risk factor for skin cancer patients. This finding has fuelled efforts to understand the mechanisms involved in the immune suppression induced by exposure to UV radiation. This article reviews the recent findings on the role of epidermal cytokines in the generation of an immune response and their role in the induction of immune suppression induced by UV exposure. (UK)

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.

Examining structural and clinical factors associated with implementation of standing orders for adult immunization.

Science.gov (United States)

Yonas, Michael A; Nowalk, Mary Patricia; Zimmerman, Richard K; Ahmed, Faruque; Albert, Steven M

2012-01-01

A proven method to increase vaccination rates in primary care is a standing orders program (SOP) for nonphysician staff to assess and vaccinate eligible individuals without a specific written physician order. This study describes a mixed methods approach to examining physicians' beliefs and attitudes about and adoption of SOPs for adult immunizations, specifically, influenza and pneumococcal polysaccharide vaccine. Focus groups and in-depth interviews of physicians, nurses, practice managers, and the medical director of a managed care health plan were conducted. Results were used to enrich a concise survey based on the Awareness-to-Adherence model of physician behavior and previous research, which was mailed to 1,640 general internists and family physicians nationwide. Barriers to SOPs identified through qualitative methods were lack of interest in changing the status quo, a physician-dominated hierarchy, and fear of malpractice. Facilitators included having an electronic medical record and a practice culture that was open to change. The survey (response rate 67%) confirmed the facilitators and further identified patient, physician, and practice factors that served as barriers to establishing and maintaining SOPs. This mixed methods approach provided the opportunity to develop a tailored and practice-oriented survey for examining the contextual factors influencing clinical providers' decisions to implement SOPs for adult immunization. © 2011 National Association for Healthcare Quality.

Role of Cortistatin in the Stressed Immune System.

Science.gov (United States)

Delgado, Mario; Gonzalez-Rey, Elena

2017-01-01

The immune system is faced with the daunting job of defending the organism against invading pathogens, while at the same time preserving the body integrity and maintaining tolerance to its own tissues. Loss of self-tolerance compromises immune homeostasis and leads to the onset of autoimmune disorders. The identification of endogenous factors that control immune tolerance and inflammation is a key goal for immunologists. Evidences from the last decade indicate that the neuropeptide cortistatin is one of the endogenous factors. Cortistatin is produced by immune cells and through its binding to various receptors, it exerts potent anti-inflammatory actions and participates in the maintenance of immune tolerance at multiple levels, especially in immunological disorders. Cortistatin emerges as a key element in the bidirectional communication between the neuroendocrine and immune systems aimed at regulating body homeostasis. © 2017 S. Karger AG, Basel.

Rebuilding immunity with Remune.

Science.gov (United States)

Whitfield, L

1998-01-01

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

Immune mediated liver failure.

Science.gov (United States)

Wang, Xiaojing; Ning, Qin

2014-01-01

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

CCR6-dependent positioning of memory B cells is essential for their ability to mount a recall response to antigen

Science.gov (United States)

Elgueta, Raul; Marks, Ellen; Nowak, Elizabeth; Menezes, Shinelle; Benson, Micah; Raman, Vanitha S.; Ortiz, Carla; O’Connell, Samuel; Hess, Henry; Lord, Graham M.; Noelle, Randolph

2014-01-01

Chemokine-dependent localization of specific B cell subsets within the immune microarchitecture is essential to insure successful cognate interactions. While cognate interactions between T cells and memory B cells (Bmem)5 are essential for the secondary humoral immune responses, the chemokine response patterns of Bmem cells are largely unknown. In contrast to naïve B cells, this study shows that antigen-specific Bmem cells have heightened expression of CCR6 and a selective chemotactic response to the CCR6 ligand, CCL20. While CCR6 appears be non-essential for the initial clonal expansion and maintenance of Bmem, CCR6 is essential for the ability of Bmem to respond to a recall response to their cognate antigen. This dependency was deemed intrinsic by studies in CCR6-deficient mice and in bone-marrow chimeric mice where CCR6 deficiency was limited to the B cell lineage. Finally, the mis-positioning of CCR6-deficient Bmem was revealed by immunohistological analysis with an altered distribution of CCR6-deficient Bmem from the marginal and perifollicular to the follicular/germinal center area. PMID:25505290

Trauma: the role of the innate immune system

Directory of Open Access Journals (Sweden)

Rijkers GT

2006-05-01

Full Text Available Abstract Immune dysfunction can provoke (multiple organ failure in severely injured patients. This dysfunction manifests in two forms, which follow a biphasic pattern. During the first phase, in addition to the injury by trauma, organ damage is caused by the immune system during a systemic inflammatory response. During the second phase the patient is more susceptible for sepsis due to host defence failure (immune paralysis. The pathophysiological model outlined in this review encompasses etiological factors and the contribution of the innate immune system in the end organ damage. The etiological factors can be divided into intrinsic (genetic predisposition and physiological status and extrinsic components (type of injury or "traumaload" and surgery or "intervention load". Of all the factors, the intervention load is the only one which, can be altered by the attending emergency physician. Adjustment of the therapeutic approach and choice of the most appropriate treatment strategy can minimize the damage caused by the immune response and prevent the development of immunological paralysis. This review provides a pathophysiological basis for the damage control concept, in which a staged approach of surgery and post-traumatic immunomonitoring have become important aspects of the treatment protocol. The innate immune system is the main objective of immunomonitoring as it has the most prominent role in organ failure after trauma. Polymorphonuclear phagocytes and monocytes are the main effector-cells of the innate immune system in the processes that lead to organ failure. These cells are controlled by cytokines, chemokines, complement factors and specific tissue signals. The contribution of tissue barrier integrity and its interaction with the innate immune system is further evaluated.

Promoting tissue regeneration by modulating the immune system.

Science.gov (United States)

Julier, Ziad; Park, Anthony J; Briquez, Priscilla S; Martino, Mikaël M

2017-04-15

The immune system plays a central role in tissue repair and regeneration. Indeed, the immune response to tissue injury is crucial in determining the speed and the outcome of the healing process, including the extent of scarring and the restoration of organ function. Therefore, controlling immune components via biomaterials and drug delivery systems is becoming an attractive approach in regenerative medicine, since therapies based on stem cells and growth factors have not yet proven to be broadly effective in the clinic. To integrate the immune system into regenerative strategies, one of the first challenges is to understand the precise functions of the different immune components during the tissue healing process. While remarkable progress has been made, the immune mechanisms involved are still elusive, and there is indication for both negative and positive roles depending on the tissue type or organ and life stage. It is well recognized that the innate immune response comprising danger signals, neutrophils and macrophages modulates tissue healing. In addition, it is becoming evident that the adaptive immune response, in particular T cell subset activities, plays a critical role. In this review, we first present an overview of the basic immune mechanisms involved in tissue repair and regeneration. Then, we highlight various approaches based on biomaterials and drug delivery systems that aim at modulating these mechanisms to limit fibrosis and promote regeneration. We propose that the next generation of regenerative therapies may evolve from typical biomaterial-, stem cell-, or growth factor-centric approaches to an immune-centric approach. Most regenerative strategies have not yet proven to be safe or reasonably efficient in the clinic. In addition to stem cells and growth factors, the immune system plays a crucial role in the tissue healing process. Here, we propose that controlling the immune-mediated mechanisms of tissue repair and regeneration may support

Host-microbiota interplay in mediating immune disorders.

Science.gov (United States)

Felix, Krysta M; Tahsin, Shekha; Wu, Hsin-Jung Joyce

2018-04-01

To maintain health, the immune system must maintain a delicate balance between eliminating invading pathogens and avoiding immune disorders such as autoimmunity and allergies. The gut microbiota provide essential health benefits to the host, particularly by regulating immune homeostasis. Dysbiosis, an alteration and imbalance of the gut microbiota, is associated with the development of several autoimmune diseases in both mice and humans. In this review, we discuss recent advances in understanding how certain factors, such as age and gender, affect the gut microbiota, which in turn can influence the development of autoimmune diseases. The age factor in microbiota-dependent immune disorders indicates a window of opportunity for future diagnostic and therapeutic approaches. We also discuss unique commensal bacteria with strong immunomodulatory activity. Finally, we provide an overview of the potential molecular mechanisms whereby gut microbiota induce autoimmunity, as well as the evidence that gut microbiota trigger extraintestinal diseases by inducing the migration of gut-derived immune cells. Elucidating the interaction of gut microbiota and the host immune system will help us understand the pathogenesis of immune disorders, and provide us with new foundations to develop novel immuno- or microbe-targeted therapies. © 2017 New York Academy of Sciences.

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...

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

Science.gov (United States)

Wen, Yun; van Heuven, Walter J B

2017-06-01

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.

Tetanus toxoid immunization coverage among mothers of below one ...

African Journals Online (AJOL)

Poverty and lack of health facilities also contributed to the low level of immunization coverage. For TT immunization to improve in the area studied, factors impeding immunization must be addressed. Keywords: tetanus, immunization, coverage. African Journal of Clinical and Experimental Microbiology Vol. 6 (3) 2005: 233- ...

Incomplete immune recovery in HIV infection

DEFF Research Database (Denmark)

Gaardbo, Julie C; Hartling, Hans J; Gerstoft, Jan

2012-01-01

-infected patients do not achieve optimal immune reconstitution despite suppression of viral replication. These patients are referred to as immunological nonresponders (INRs). INRs present with severely altered immunological functions, including malfunction and diminished production of cells within lymphopoetic...... tissue, perturbed frequencies of immune regulators such as regulatory T cells and Th17 cells, and increased immune activation, immunosenescence, and apoptosis. Importantly, INRs have an increased risk of morbidity and mortality compared to HIV-infected patients with an optimal immune reconstitution....... Additional treatment to HAART that may improve immune reconstitution has been investigated, but results thus far have proved disappointing. The reason for immunological nonresponse is incompletely understood. This paper summarizes the known and unknown factors regarding the incomplete immune reconstitution...

Sensing miRNA: Signal Amplification by Cognate RISC for Intracellular Detection of miRNA in Live Cells.

Science.gov (United States)

Kavishwar, Amol; Medarova, Zdravka

2016-01-01

The ability to detect miRNA expression in live cells would leave these cells available for further manipulation or culture. Here, we describe the design of a miRNA sensor oligonucleotide whose sequence mimics the target mRNA. The sensor has a fluorescent label on one end of the oligo and a quencher on the other. When inside the cell, the sensor is recognized by its cognate miRNA-RISC and gets cleaved, setting the fluorophore free from its quencher. This results in fluorescence "turn on." Since cleavage by the RISC complex is an enzymatic process, the described approach has a very high level of sensitivity (nM). The rate of nonspecific cleavage of the sensor is very slow permitting the collection of meaningful signal over a long period of time.

The Necrosome Promotes Pancreas 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

2016-01-01

Neoplastic pancreatic epithelial cells are widely believed to die via Caspase 8-dependant apoptotic cell death and chemotherapy is thought to further promote tumor apoptosis1. Conversely, disruption of apoptosis is a basic modality cancer cells exploit for survival2,3. However, the role of necroptosis, or programmed necrosis, in pancreatic ductal adenocarcinoma (PDA) is uncertain. There are a multitude of potential inducers of necroptosis in PDA including ligation of TNFR1, CD95, TRAIL receptors, Toll-like receptors, ROS, and Chemotherapeutics4,5. Here we report that the principal components of the necrosome, RIP1 and RIP3, are highly expressed in PDA and are further upregulated by chemotherapy. Blockade of the necrosome in vitro promoted cancer cell proliferation and induced an aggressive oncogenic phenotype. By contrast, in vivo RIP3 deletion or RIP1 inhibition was protective against oncogenic progression and was associated with the development of a highly immunogenic myeloid and T cell infiltrate. The immune-suppressive tumor microenvironment (TME) associated with intact RIP1/RIP3 signaling was in-part contingent on necroptosis-induced CXCL1 expression whereas CXCL1 blockade was protective against PDA. Moreover, we found that cytoplasmic SAP130 was expressed in PDA in a RIP1/RIP3-dependent manner, and Mincle – its cognate receptor – was upregulated in tumor-infiltrating myeloid cells. Mincle ligation by SAP130 promoted oncogenesis whereas Mincle deletion was protective and phenocopied the immunogenic reprogramming of the TME characteristic of RIP3 deletion. Cellular depletion experiments suggested that whereas inhibitory macrophages promote tumorigenesis in PDA, they lose their immune-suppressive effects in the context of RIP3 or Mincle deletion. As such, T cells which are dispensable to PDA progression in hosts with intact RIP3 or Mincle signaling become reprogrammed into indispensable mediators of anti-tumor immunity in absence of RIP3 or Mincle. Our work

Toll-like receptors and interferon associated immune factors responses to spring viraemia of carp virus infection in common carp (Cyprinus carpio).

Science.gov (United States)

Wei, Xinxian; Li, Xiao Zheng; Zheng, Xiaocong; Jia, Peng; Wang, Jinjin; Yang, Xianle; Yu, Li; Shi, Xiujie; Tong, Guixiang; Liu, Hong

2016-08-01

Pattern recognition receptor (PRR) toll-like receptors (TLRs), antiviral agent interferon (IFN) and the effector IFN stimulated genes (ISGs) play a fundamental role in the innate immune response against viruses among all vertebrate classes. Common carp is a host for spring viraemia of carp virus (Rhabdovirus carpio, SVCV), which belong to Rhabdoviridae family. The present in-vivo experiment was conducted to investigate the expression of these innate immune factors in early phase as well as during recovery of SVCV infection by real-time quantitative reverse transcriptase polymerase chain reaction. A less lethal SVCV infection was generated in common carp (Cyprinus carpio) and was sampled at 3, 6, 12 h post infection (hpi), 1, 3, 5, 7 and 10 days post infection (dpi). At 3 hpi, the SVCV N gene was detected in all three fish and all three fish showed a relative fold increase of TLR2, TLR3 and TLR7, IFNa1, ISG15 and Vig1. Viral copies rapidly increased at 12 hpi then remained high until 5 dpi. When viral copy numbers were high, a higher expression of immune genes TLR2, TLR3, TLR7, IFNa1, IFNa2, IFNa1S, IFN regulatory factor 3 (IRF3), IRF7, interleukin 1β (IL1β), IL6, IL10, ADAR, ISG15, Mx1, PKR and Vig1 were observed. Viral copies were gradually reduced in 5 to 10 dpi fish, and also the immune response was considerably reduced but remained elevated. A high degree of correlation was observed between immune genes and viral copy number in each of the sampled fish at 12 hpi. The quick and prolonged elevated expression of the immune genes indicates their crucial role in survival of host against SVCV. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Immune Evasion Strategies and Persistence of Helicobacter pylori.

Science.gov (United States)

Mejías-Luque, Raquel; Gerhard, Markus

Helicobacter pylori infection is commonly acquired during childhood, can persist lifelong if not treated, and can cause different gastric pathologies, including chronic gastritis, peptic ulcer disease, and eventually gastric cancer. H. pylori has developed a number of strategies in order to cope with the hostile conditions found in the human stomach as well as successful mechanisms to evade the strong innate and adaptive immune responses elicited upon infection. Thus, by manipulating innate immune receptors and related signaling pathways, inducing tolerogenic dendritic cells and inhibiting effector T cell responses, H. pylori ensures low recognition by the host immune system as well as its persistence in the gastric epithelium. Bacterial virulence factors such as cytotoxin-associated gene A, vacuolating cytotoxin A, or gamma-glutamyltranspeptidase have been extensively studied in the context of bacterial immune escape and persistence. Further, the bacterium possesses other factors that contribute to immune evasion. In this chapter, we discuss in detail the main evasion and persistence strategies evolved by the bacterium as well as the specific bacterial virulence factors involved.

Season of birth shapes neonatal immune function

DEFF Research Database (Denmark)

Thysen, Anna Hammerich; Rasmussen, Morten Arendt; Kreiner-Møller, Eskil

2016-01-01

Birth season has been reported to be a risk factor for several immune-mediated diseases. We hypothesized that this association is mediated by differential changes in neonatal immune phenotype and function with birth season. We sought to investigate the influence of season of birth on cord blood...... immune cell subsets and inflammatory mediators in neonatal airways. Cord blood was phenotyped for 26 different immune cell subsets, and at 1 month of age, 20 cytokines and chemokines were quantified in airway mucosal lining fluid. Multivariate partial least squares discriminant analyses were applied...... to determine whether certain immune profiles dominate by birth season, and correlations between individual cord blood immune cells and early airway immune mediators were defined. We found a birth season-related fluctuation in neonatal immune cell subsets and in early-life airway mucosal immune function...

Immune mechanisms in Babesia-infected animals

International Nuclear Information System (INIS)

Phillips, R.S.

1980-01-01

The course of a Babesia infection depends on the species of host and parasite involved. Animals infected with virulent babesias may need chemotherapy before acquired immunity develops. Maintenance of immunity is not dependent on the presence of the parasite. Babesia infections are characteristically of long duration. The immune response to babesias includes both humoral and cellular components. Antibody levels detected in serodiagnostic tests do not relate to levels of resistance to the parasite. Some antibodies, however, appear to be protective. Antiparasitic antibodies may damage parasites in or outside the red cell and act as opsonins. T-cell-deficient and anti-lymphocyte-serum-treated rodents are more susceptible to rodent piroplasms indicating a role for T-cells as either helper cells and/or as mediators of cell-mediated immunity (CMI). There is indirect evidence of CMI, but the cell-mediated mechanisms involved in parasite killing are not known. In domestic animals immunity is largely species- and strain-specific. Antigenic variation by babesias occurs. In rodents, however, there is cross-immunity between different species of rodent piroplasms and between rodent piroplasms and some malaria parasites. Prior infection with agents such as BCG, and Corynebacterium parvum, gives mice non-specific resistance to rodent piroplasms possibly mediated through a soluble non-antibody factor. This factor may also be liberated during piroplasm infections and by being toxic to malaria parasites account for heterologous immunity. Active immunization against babesias has been achieved with avirulent strains, irradiated parasites and dead parasites in adjuvant. During Babesia infections the primary and, to a lesser degree, the secondary immune response to heterologous antigens can be depressed. Maximum depression coincides with peak parasitaemia when antigen priming may be abolished completely. Immunosuppression during Babesia infections can prolong or exacerbate concurrent

Primary Immunization Status In Rural Block Of Kanpur District

Directory of Open Access Journals (Sweden)

S K Kaushal

2009-06-01

Full Text Available Research question: What is the status of primary immunization of children in the age group of 12-23 month Objective: To assess the status of Primary immunization in age group of 12 to 23 month Children, To compare the primary immunization in intensive and twilight villages, To study the influence of socialfactors affecting immunization & Tofind out reasons for immunization default Study design: cross sectional study Setting and participants: rural block of.Kanpur District and mothers ofchildren in age group of 12-23 months. Study period: July to December 2005 Sample size: 280 mothers of study group children. Study variable: Immunization status, socialfactors, vaccine, reasons for immunization default Results : 32.85% of children were fully immunized. Highest (92.85% covered antigen were found as OPV-1 and lowest (41.78% covered antigen as DPT-3.Literacy and joint family had positive impact on immunization status. The main reasons were observed for immunization default as ignorance (about need/place/person/time and distance factor. Conclusion : Quantity1 wise coverage was quite satisfactory. High dropout rate due to ignorance and distance factors should be taken into

Evolution of transgenerational immunity in invertebrates

OpenAIRE

Pigeault, R.; Garnier, R.; Rivero, A.; Gandon, S.

2016-01-01

Over a decade ago, the discovery of transgenerational immunity in invertebrates shifted existing paradigms on the lack of sophistication of their immune system. Nonetheless, the prevalence of this trait and the ecological factors driving its evolution in invertebrates remain poorly understood. Here, we develop a theoretical host–parasite model and predict that long lifespan and low dispersal should promote the evolution of transgenerational immunity. We also predict that in species that produ...

Identification of four Drosophila allatostatins as the cognate ligands for the Drosophila orphan receptor DAR-2

DEFF Research Database (Denmark)

Lenz, C; Williamson, M; Hansen, G N

2001-01-01

The allatostatins are generally inhibitory insect neuropeptides. The Drosophila orphan receptor DAR-2 is a G-protein-coupled receptor, having 47% amino acid residue identity with another Drosophila receptor, DAR-1 (which is also called dros. GPCR, or DGR) that was previously shown...... to be the receptor for an intrinsic Drosophila A-type (cockroach-type) allatostatin. Here, we have permanently expressed DAR-2 in CHO cells and found that it is the cognate receptor for four Drosophila A-type allatostatins, the drostatins-A1 to -A4. Of all the drostatins, drostatin-A4 (Thr...... weakly in the brain. The Drosophila larval gut also contains about 20-30 endocrine cells, expressing the gene for the drostatins-A1 to -A4. We suggest, therefore, that DAR-2 mediates an allatostatin (drostatin)-induced inhibition of gut motility. This is the first report on the permanent and functional...

Individual differences in maternal response to immune challenge predict offspring behavior: Contribution of environmental factors

Science.gov (United States)

Bronson, Stefanie L.; Ahlbrand, Rebecca; Horn, Paul S.; Kern, Joseph R.; Richtand, Neil M.

2011-01-01

Maternal infection during pregnancy elevates risk for schizophrenia and related disorders in offspring. Converging evidence suggests the maternal inflammatory response mediates the interaction between maternal infection, altered brain development, and behavioral outcome. The extent to which individual differences in the maternal response to immune challenge influence the development of these abnormalities is unknown. The present study investigated the impact of individual differences in maternal response to the viral mimic polyinosinic:polycytidylic acid (poly I:C) on offspring behavior. We observed significant variability in body weight alterations of pregnant rats induced by administration of poly I:C on gestational day 14. Furthermore, the presence or absence of maternal weight loss predicted MK-801 and amphetamine stimulated locomotor abnormalities in offspring. MK-801 stimulated locomotion was altered in offspring of all poly I:C treated dams; however, the presence or absence of maternal weight loss resulted in decreased and modestly increased locomotion, respectively. Adult offspring of poly I:C treated dams that lost weight exhibited significantly decreased amphetamine stimulated locomotion, while offspring of poly I:C treated dams without weight loss performed similarly to vehicle controls. Social isolation and increased maternal age predicted weight loss in response to poly I:C but not vehicle injection. In combination, these data identify environmental factors associated with the maternal response to immune challenge and functional outcome of offspring exposed to maternal immune activation. PMID:21255612

Immune Response to Lipoproteins in Atherosclerosis

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Sonia Samson

2012-01-01

Full Text Available Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by chronic inflammation and altered immune response. Cholesterol is a well-known risk factor associated with the development of cardiovascular diseases. Elevated serum cholesterol is unique because it can lead to development of atherosclerosis in animals and humans even in the absence of other risk factors. Modifications of low-density lipoproteins mediated by oxidation, enzymatic degradation, and aggregation result in changes in their function and activate both innate and adaptive immune system. Oxidized low-density lipoprotein (LDL has been identified as one of the most important autoantigens in atherosclerosis. This escape from self-tolerance is dependent on the formation of oxidized phospholipids. The emerging understanding of the importance of immune responses against oxidized LDL in atherosclerosis has focused attention on the possibility of development of novel therapy for atherosclerosis. This review provides an overview of immune response to lipoproteins and the fascinating possibility of developing an immunomodulatory therapy for atherosclerosis.

Knowledge, attitude and practice of childhood immunization among ...

African Journals Online (AJOL)

Background and Objectives: Vaccine preventable diseases cause significant morbidity ... This study determined childhood immunization uptake and associated factors ... The commonest immunizations missed were measles and yellow fever.

Addiction, adolescence, and innate immune gene induction

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Fulton T Crews

2011-04-01

Full Text Available Repeated drug use/abuse amplifies psychopathology, progressively reducing frontal lobe behavioral control and cognitive flexibility while simultaneously increasing limbic temporal lobe negative emotionality. The period of adolescence is a neurodevelopmental stage characterized by poor behavioral control as well as strong limbic reward and thrill seeking. Repeated drug abuse and/or stress during this stage increase the risk of addiction and elevate activator innate immune signaling in the brain. Nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-κB is a key glial transcription factor that regulates proinflammatory chemokines, cytokines, oxidases, proteases, and other innate immune genes. Induction of innate brain immune gene expression (e.g., NF-κB facilitates negative affect, depression-like behaviors, and inhibits hippocampal neurogenesis. In addition, innate immune gene induction alters cortical neurotransmission consistent with loss of behavioral control. Studies with anti-oxidant, anti-inflammatory, and anti-depressant drugs as well as opiate antagonists link persistent innate immune gene expression to key behavioral components of addiction, e.g. negative affect-anxiety and loss of frontal cortical behavioral control. This review suggests that persistent and progressive changes in innate immune gene expression contribute to the development of addiction. Innate immune genes may represent a novel new target for addiction therapy.

Measuring the immune system: a comprehensive approach for the analysis of immune functions in humans.

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Claus, Maren; Dychus, Nicole; Ebel, Melanie; Damaschke, Jürgen; Maydych, Viktoriya; Wolf, Oliver T; Kleinsorge, Thomas; Watzl, Carsten

2016-10-01

The immune system is essential to provide protection from infections and cancer. Disturbances in immune function can therefore directly affect the health of the affected individual. Many extrinsic and intrinsic factors such as exposure to chemicals, stress, nutrition and age have been reported to influence the immune system. These influences can affect various components of the immune system, and we are just beginning to understand the causalities of these changes. To investigate such disturbances, it is therefore essential to analyze the different components of the immune system in a comprehensive fashion. Here, we demonstrate such an approach which provides information about total number of leukocytes, detailed quantitative and qualitative changes in the composition of lymphocyte subsets, cytokine levels in serum and functional properties of T cells, NK cells and monocytes. Using samples from a cohort of 24 healthy volunteers, we demonstrate the feasibility of our approach to detect changes in immune functions.

Altered Immune Regulation in Type 1 Diabetes

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

2013-01-01

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

Altered Immune Regulation in Type 1 Diabetes

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András Zóka

2013-01-01

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

Research progress in neuro-immune interactions in Caenorhabditis elegans

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Jin-ling CAI

2012-09-01

Full Text Available The innate immune response may be activated quickly once the organism is invaded by exotic pathogens. An excessive immune response may result in inflammation and tissue damage, whereas an insufficient immune response may result in infection. Nervous system may regulate the intensity of innate immune responses by releasing neurotransmitters, neuropeptides and hormones. Compared with the complicated neuro-immune system in mammals, it is much simpler in Caenorhabditis elegans. Besides, C. elegans is accessible to genetic, molecular biology and behavioral analyses, so it has been used in studies on neuro-immune interactions. It has been revealed recently in the studies with C. elegans that the neuronal pathways regulating innate immune responses primarily include a transforming growth factor-β (TGF-β pathway, an insulin/insulin-like growth factor receptor (IGF pathway and dopaminergic neurotransmission. Since these pathways are evolutionally conservative, so it might be able to provide some new ideas for the research on neuro-immune interactions at molecular levels. The recent progress in this field has been reviewed in present paper.

Staphylococcal Immune Evasion Proteins: Structure, Function, and Host Adaptation.

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Koymans, Kirsten J; Vrieling, Manouk; Gorham, Ronald D; van Strijp, Jos A G

2017-01-01

Staphylococcus aureus is a successful human and animal pathogen. Its pathogenicity is linked to its ability to secrete a large amount of virulence factors. These secreted proteins interfere with many critical components of the immune system, both innate and adaptive, and hamper proper immune functioning. In recent years, numerous studies have been conducted in order to understand the molecular mechanism underlying the interaction of evasion molecules with the host immune system. Structural studies have fundamentally contributed to our understanding of the mechanisms of action of the individual factors. Furthermore, such studies revealed one of the most striking characteristics of the secreted immune evasion molecules: their conserved structure. Despite high-sequence variability, most immune evasion molecules belong to a small number of structural categories. Another remarkable characteristic is that S. aureus carries most of these virulence factors on mobile genetic elements (MGE) or ex-MGE in its accessory genome. Coevolution of pathogen and host has resulted in immune evasion molecules with a highly host-specific function and prevalence. In this review, we explore how these shared structures and genomic locations relate to function and host specificity. This is discussed in the context of therapeutic options for these immune evasion molecules in infectious as well as in inflammatory diseases.

Active and passive immunity, vaccine types, excipients and licensing.

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Baxter, David

2007-12-01

Abstract Immunity is the state of protection against infectious disease conferred either through an immune response generated by immunization or previous infection or by other non-immunological factors. This article reviews active and passive immunity and the differences between them: it also describes the four different commercially available vaccine types (live attenuated, killed/inactivated, subunit and toxoid): it also looks at how these different vaccines generate an adaptive immune response.

[The liver and the immune system].

Science.gov (United States)

Jakab, Lajos

2015-07-26

The liver is known to be the metabolic centre of the organism and is under the control of the central nervous system. It has a peculiar tissue structure and its anatomic localisation defines it as part of the immune system having an individual role in the defence of the organism. The determinant of its particular tissue build-up is the sinusoid system. In addition to hepatocytes, one cell row "endothelium", stellate cells close to the external surface, Kupffer cells tightly to its inner surface, as well as dendritic cells and other cell types (T and B lymphocytes, natural killer and natural killer T-cells, mast cells, granulocytes) are present. The multitudes and variety of cells make it possible to carry out the tasks according to the assignment of the organism. The liver is a member of the immune system having immune cells largely in an activated state. Its principal tasks are the assurance of the peripheral immune tolerance of the organism with the help of the haemopoetic cells and transforming growth factor-β. The liver takes part in the determination of the manner of the non-specific immune response of the organism. In addition to acute phase reaction of the organism, the liver has a role in the adaptive/specific immune response. These functions include retardation of the T and B lymphocytes and the defence against harmful pathogens. With the collaboration of transforming growth factor-β, immunoglobulins and their subclasses are inhibited just as the response of the T lymphocytes. The only exception is the undisturbed immunoglobulin A production. Particularly important is the intensive participation of the liver in the acute phase reaction of the organism, which is organised and guided by the coordinated functions of the cortico-hypothalamo-hypophysis-adrenal axis. Beside cellular elements, hormones, adhesion molecules, chemokines and cytokines are also involved in the cooperation with the organs. Acute phase reactants play a central role in these processes

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

DEFF Research Database (Denmark)

Højbøge, Tina Rødgaard

state of low-grade inflammation in the adipose tissues, which involves several factors of the innate immune response having a range of systemic effects and which has been implicated in the development of the metabolic syndrome. To investigate the impact of obesity and obesity-related diseases good...... translational animal models are needed, and as such pigs have been proposed as relevant models for human obesity-induced inflammation as pigs share many genetic, anatomical and physiological features with humans. In this project the up- and downregulation of genes and proteins involved in the innate immune...... 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...

Determinants Of Missed Opportunities For Immunization Among ...

African Journals Online (AJOL)

Factors responsible for the missed opportunities included the attitude of the health worker, prolonged time of waiting to receive vaccine, immunization clashing with other schedules and transportation problem. Respondents' level ofknowledge on immunization and educational background were significantly associated with ...

The Tomato Fni3 Lysine-63–Specific Ubiquitin-Conjugating Enzyme and Suv Ubiquitin E2 Variant Positively Regulate Plant Immunity[C][W

Science.gov (United States)

Mural, Ravi V.; Liu, Yao; Rosebrock, Tracy R.; Brady, Jennifer J.; Hamera, Sadia; Connor, Richard A.; Martin, Gregory B.; Zeng, Lirong

2013-01-01

The activation of an immune response in tomato (Solanum lycopersicum) against Pseudomonas syringae relies on the recognition of E3 ligase–deficient forms of AvrPtoB by the host protein kinase, Fen. To investigate the mechanisms by which Fen-mediated immunity is regulated, we characterize in this study a Fen-interacting protein, Fni3, and its cofactor, S. lycoperiscum Uev (Suv). Fni3 encodes a homolog of the Ubc13-type ubiquitin-conjugating enzyme that catalyzes exclusively Lys-63–linked ubiquitination, whereas Suv is a ubiquitin-conjugating enzyme variant. The C-terminal region of Fen was necessary for interaction with Fni3, and this interaction was required for cell death triggered by overexpression of Fen in Nicotiana benthamiana leaves. Fni3 was shown to be an active E2 enzyme, but Suv displayed no ubiquitin-conjugating activity; Fni3 and Suv together directed Lys-63–linked ubiquitination. Decreased expression of Fni3, another tomato Ubc13 homolog, Sl-Ubc13-2, or Suv in N. benthamiana leaves diminished cell death associated with Fen-mediated immunity and cell death elicited by several other resistance (R) proteins and their cognate effectors. We also discovered that coexpression of Fen and other R proteins/effectors with a Fni3 mutant that is compromised for ubiquitin-conjugating activity diminished the cell death. These results suggest that Fni3/Sl-Ubc13-2 and Suv regulate the immune response mediated by Fen and other R proteins through Lys-63–linked ubiquitination. PMID:24076975

Nubbin isoform antagonism governs Drosophila intestinal immune homeostasis.

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Bo G Lindberg

2018-03-01

Full Text Available Gut immunity is regulated by intricate and dynamic mechanisms to ensure homeostasis despite a constantly changing microbial environment. Several regulatory factors have been described to participate in feedback responses to prevent aberrant immune activity. Little is, however, known about how transcriptional programs are directly tuned to efficiently adapt host gut tissues to the current microbiome. Here we show that the POU/Oct gene nubbin (nub encodes two transcription factor isoforms, Nub-PB and Nub-PD, which antagonistically regulate immune gene expression in Drosophila. Global transcriptional profiling of adult flies overexpressing Nub-PB in immunocompetent tissues revealed that this form is a strong transcriptional activator of a large set of immune genes. Further genetic analyses showed that Nub-PB is sufficient to drive expression both independently and in conjunction with nuclear factor kappa B (NF-κB, JNK and JAK/STAT pathways. Similar overexpression of Nub-PD did, conversely, repress expression of the same targets. Strikingly, isoform co-overexpression normalized immune gene transcription, suggesting antagonistic activities. RNAi-mediated knockdown of individual nub transcripts in enterocytes confirmed antagonistic regulation by the two isoforms and that both are necessary for normal immune gene transcription in the midgut. Furthermore, enterocyte-specific Nub-PB expression levels had a strong impact on gut bacterial load as well as host lifespan. Overexpression of Nub-PB enhanced bacterial clearance of ingested Erwinia carotovora carotovora 15. Nevertheless, flies quickly succumbed to the infection, suggesting a deleterious immune response. In line with this, prolonged overexpression promoted a proinflammatory signature in the gut with induction of JNK and JAK/STAT pathways, increased apoptosis and stem cell proliferation. These findings highlight a novel regulatory mechanism of host-microbe interactions mediated by antagonistic

Mycobacterium tuberculosis UvrD1 and UvrA proteins suppress DNA strand exchange promoted by cognate and noncognate RecA proteins.

Science.gov (United States)

Singh, Pawan; Patil, K Neelakanteshwar; Khanduja, Jasbeer Singh; Kumar, P Sanjay; Williams, Alan; Rossi, Franca; Rizzi, Menico; Davis, Elaine O; Muniyappa, K

2010-06-15

DNA helicases are present in all kingdoms of life and play crucial roles in processes of DNA metabolism such as replication, repair, recombination, and transcription. To date, however, the role of DNA helicases during homologous recombination in mycobacteria remains unknown. In this study, we show that Mycobacterium tuberculosis UvrD1 more efficiently inhibited the strand exchange promoted by its cognate RecA, compared to noncognate Mycobacterium smegmatis or Escherichia coli RecA proteins. The M. tuberculosis UvrD1(Q276R) mutant lacking the helicase and ATPase activities was able to block strand exchange promoted by mycobacterial RecA proteins but not of E. coli RecA. We observed that M. tuberculosis UvrA by itself has no discernible effect on strand exchange promoted by E. coli RecA but impedes the reaction catalyzed by the mycobacterial RecA proteins. Our data also show that M. tuberculosis UvrA and UvrD1 can act together to inhibit strand exchange promoted by mycobacterial RecA proteins. Taken together, these findings raise the possibility that UvrD1 and UvrA might act together in vivo to counter the deleterious effects of RecA nucleoprotein filaments and/or facilitate the dissolution of recombination intermediates. Finally, we provide direct experimental evidence for a physical interaction between M. tuberculosis UvrD1 and RecA on one hand and RecA and UvrA on the other hand. These observations are consistent with a molecular mechanism, whereby M. tuberculosis UvrA and UvrD1, acting together, block DNA strand exchange promoted by cognate and noncognate RecA proteins.

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.

New clues in the nucleus: Transcriptional reprogramming in effector-triggered immunity

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SAIKAT eBHATTACHARJEE

2013-09-01

Full Text Available The robustness of plant effector-triggered immunity is correlated with massive alterations of the host transcriptome. Yet the molecular mechanisms that cause and underlie this reprogramming remain obscure. Here we will review recent advances in deciphering nuclear functions of plant immune receptors and of associated proteins. Important open questions remain, such as the identities of the primary transcription factors involved in control of effector-triggered immune responses, and indeed whether this can be generalized or whether particular effector-resistance protein interactions impinge on distinct sectors in the transcriptional response web. Multiple lines of evidence have implicated WRKY transcription factors at the core of responses to microbe-associated molecular patterns and in intersections with effector-triggered immunity. Recent findings from yeast two-hybrid studies suggest that members of the TCP transcription factor family are targets of several effectors from diverse pathogens. Additional transcription factor families that are directly or indirectly involved in effector-triggered immunity are likely to be identified.

[Effect of vitamine A on mice immune response induced by specific periodontal pathogenic bacteria-immunization].

Science.gov (United States)

Lin, Xiao-Ping; Zhou, Xiao-Jia; Liu, Hong-Li; DU, Li-Li; Toshihisa, Kawai

2010-12-01

The aim of this study was to investigate the effect of vitamine-A deficiency on the induction of specific periodontal pathogenic bacteria A. actinomycetetemcomitans(Aa) immunization. BALB/c mice were fed with vitamine A-depleted diet or control regular diet throughout the whole experiment period. After 2 weeks, immunized formalin-killed Aa to build immunized models, 6 weeks later, sacrificed to determine specific antibody-IgG, IgM and sub-class IgG antibody titers in serum, and concentration of IL-10, IFN-γ, TNF-α and RANKL in T cell supernatant were measured by ELISA and T cell proliferation was measured by cintilography. SPSS 11.5 software package was used for statistical analysis. The levels of whole IgG and IgM antibody which were immunized by Aa significantly elevated, non-immune group was unable to produce any antibody. Compared with Aa immunized+RD group, the level of whole IgG in Aa immunized+VAD group was significantly higher (Pvitamin-A diet can increase the immunized mice's susceptibility to periodontal pathogenic bacteria and trigger or aggravate immune inflammatory response. Adequate vitamin A is an important factor in maintaining body health. Supported by Natural Science Foundation of Liaoning Province (Grant No.20092139) and Science and Technology Program of Shenyang Municipality (Grant No.F10-149-9-32).

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

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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

Prenatal Alcohol Exposure and the Developing Immune System

OpenAIRE

Gauthier, Theresa W.

2015-01-01

Evidence from research in humans and animals suggest that ingesting alcohol during pregnancy can disrupt the fetal immune system and result in an increased risk of infections and disease in newborns that may persist throughout life. Alcohol may have indirect effects on the immune system by increasing the risk of premature birth, which itself is a risk factor for immune-related problems. Animal studies suggest that alcohol exposure directly disrupts the developing immune system. A comprehensiv...

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.

Immune Mechanisms in Myelodysplastic Syndrome

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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.

CCR6-dependent positioning of memory B cells is essential for their ability to mount a recall response to antigen.

Science.gov (United States)

Elgueta, Raul; Marks, Ellen; Nowak, Elizabeth; Menezes, Shinelle; Benson, Micah; Raman, Vanitha S; Ortiz, Carla; O'Connell, Samuel; Hess, Henry; Lord, Graham M; Noelle, Randolph

2015-01-15

Chemokine-dependent localization of specific B cell subsets within the immune microarchitecture is essential to ensure successful cognate interactions. Although cognate interactions between T cells and memory B cells (B(mem)) are essential for the secondary humoral immune responses, the chemokine response patterns of B(mem) cells are largely unknown. In contrast to naive B cells, this study shows that Ag-specific B(mem) cells have heightened expression of CCR6 and a selective chemotactic response to the CCR6 ligand, CCL20. Although CCR6 appears be nonessential for the initial clonal expansion and maintenance of B(mem), CCR6 is essential for the ability of B(mem) to respond to a recall response to their cognate Ag. This dependency was deemed intrinsic by studies in CCR6-deficient mice and in bone marrow chimeric mice where CCR6 deficiency was limited to the B cell lineage. Finally, the mis-positioning of CCR6-deficient B(mem) was revealed by immunohistological analysis with an altered distribution of CCR6-deficient B(mem) from the marginal and perifollicular to the follicular/germinal center area. Copyright © 2015 by The American Association of Immunologists, Inc.

Ancient duplications and functional divergence in the interferon regulatory factors of vertebrates provide insights into the evolution of vertebrate immune systems.

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Du, Kang; Zhong, Zaixuan; Fang, Chengchi; Dai, Wei; Shen, Yanjun; Gan, Xiaoni; He, Shunping

2018-04-01

Interferon regulatory factors (IRFs) were first discovered as transcription factors that regulate the transcription of human interferon (IFN)-β. Increasing evidence shows that they might be important players involved in Adaptive immune system (AIS) evolution. Although numbers of IRFs have been identified in chordates, the evolutionary history and functional diversity of this gene family during the early evolution of vertebrates have remained obscure. Using IRF HMM profile and HMMER searches, we identified 148 IRFs in 11 vertebrates and 4 protochordates. For them, we reconstructed the phylogenetic relationships, determined the synteny conservation, investigated the profile of natural selection, and analyzed the expression patterns in four "living fossil" vertebrates: lamprey, elephant shark, coelacanth and bichir. The results from phylogeny and synteny analysis imply that vertebrate IRFs evolved from three predecessors, instead of four as suggested in a previous study, as results from an ancient duplication followed by special expansions and lost during the vertebrate evolution. The profile of natural selection and expression reveals functional dynamics during the process. Together, they suggest that the 2nd whole-genome duplication (2WGD) provided raw materials for innovation in the IRF family, and that the birth of type-I IFN might be an important factor inducing the establishment of IRF-mediated immune networks. As a member involved in the AIS evolution, IRF provide insights into the process and mechanism involved in the complexity and novelties of vertebrate immune systems. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Aging of immune system: Immune signature from peripheral blood lymphocyte subsets in 1068 healthy adults.

Science.gov (United States)

Qin, Ling; Jing, Xie; Qiu, Zhifeng; Cao, Wei; Jiao, Yang; Routy, Jean-Pierre; Li, Taisheng

2016-05-01

Aging is a major risk factor for several conditions including neurodegenerative, cardiovascular diseases and cancer. Functional impairments in cellular pathways controlling genomic stability, and immune control have been identified. Biomarker of immune senescence is needed to improve vaccine response and to develop therapy to improve immune control. To identify phenotypic signature of circulating immune cells with aging, we enrolled 1068 Chinese healthy volunteers ranging from 18 to 80 years old. The decreased naïve CD4+ and CD8+ T cells, increased memory CD4+ or CD8+ T cells, loss of CD28 expression on T cells and reverse trend of CD38 and HLA-DR, were significant for aging of immune system. Conversely, the absolute counts and percentage of NK cells and CD19+B cells maintained stable in aging individuals. The Chinese reference ranges of absolute counts and percentage of peripheral lymphocyte in this study might be useful for future clinical evaluation.

Vaccination with Eimeria tenella elongation factor-1α recombinant protein induces protective immunity against E. tenella and E. maxima infections.

Science.gov (United States)

Lin, Rui-Qing; Lillehoj, Hyun S; Lee, Seung Kyoo; Oh, Sungtaek; Panebra, Alfredo; Lillehoj, Erik P

2017-08-30

Avian coccidiosis is caused by multiple species of the apicomplexan protozoan, Eimeria, and is one of the most economically devastating enteric diseases for the poultry industry worldwide. Host immunity to Eimeria infection, however, is relatively species-specific. The ability to immunize chickens against different species of Eimeria using a single vaccine will have a major beneficial impact on commercial poultry production. In this paper, we describe the molecular cloning, purification, and vaccination efficacy of a novel Eimeria vaccine candidate, elongation factor-1α (EF-1α). One day-old broiler chickens were given two subcutaneous immunizations one week apart with E. coli-expressed E. tenella recombinant (r)EF-1α protein and evaluated for protection against challenge infection with E. tenella or E. maxima. rEF-1α-vaccinated chickens exhibited increased body weight gains, decreased fecal oocyst output, and greater serum anti-EF-1α antibody levels following challenge infection with either E. tenella or E. maxima compared with unimmunized controls. Vaccination with EF-1α may represent a new approach to inducing cross-protective immunity against avian coccidiosis in the field. Published by Elsevier B.V.

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.

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.

Immunity to Fish Rhabdoviruses

Directory of Open Access Journals (Sweden)

Maureen K. Purcell

2012-01-01

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

Abnormal humoral immune response to influenza vaccination in pediatric type-1 human immunodeficiency virus infected patients receiving highly active antiretroviral therapy

Directory of Open Access Journals (Sweden)

Carlos J Montoya

2007-06-01

Full Text Available Given that highly active antiretroviral therapy (HAART has been demonstrated useful to restore immune competence in type-1 human immunodeficiency virus (HIV-1-infected subjects, we evaluated the specific antibody response to influenza vaccine in a cohort of HIV-1-infected children on HAART so as to analyze the quality of this immune response in patients under antiretroviral therapy. Sixteen HIV-1-infected children and 10 HIV-1 seronegative controls were immunized with a commercially available trivalent inactivated influenza vaccine containing the strains A/H1N1, A/H3N2, and B. Serum hemagglutinin inhibition (HI antibody titers were determined for the three viral strains at the time of vaccination and 1 month later. Immunization induced a significantly increased humoral response against the three influenza virus strains in controls, and only against A/H3N2 in HIV-1-infected children. The comparison of post-vaccination HI titers between HIV-1+ patients and HIV-1 negative controls showed significantly higher HI titers against the three strains in controls. In addition, post vaccination protective HI titers (defined as equal to or higher than 1:40 against the strains A/H3N2 and B were observed in a lower proportion of HIV-1+ children than in controls, while a similar proportion of individuals from each group achieved protective HI titers against the A/H1N1 strain. The CD4+ T cell count, CD4/CD8 T cells ratio, and serum viral load were not affected by influenza virus vaccination when pre- vs post-vaccination values were compared. These findings suggest that despite the fact that HAART is efficient in controlling HIV-1 replication and in increasing CD4+ T cell count in HIV-1-infected children, restoration of immune competence and response to cognate antigens remain incomplete, indicating that additional therapeutic strategies are required to achieve a full reconstitution of immune functions.

Immunomodulator, immunosuppression of radiation and immune reconstruction

International Nuclear Information System (INIS)

Mao Jianping; Fang Jing; Zhou Ying; Cui Yufang; Jiang Zhujun; Du Li; Ma Qiong

2010-01-01

There is a refined and complicated regulatory network between immune cells, and between immune cells and secretory factors. The immune system is kept in a homeostasis and equilibrium by positive activation and negative inhibition. In recent years, the mechanisms of immunosuppression in depth for successful allograft transplantation were studied, and many immunosuppressants and immunosuppressive drugs have been developed for clinical use. Most of them are targeting T cell receptors and three kinds of singnal pathways. The receptors of the immunosuppression were either found highly expressed in immune cells after irradiation. To relieve the suppression by regulating the receptors could help the immune reconstruction out of radiation damage. Many new immunoenhancers have been discovered to improve the immune system function for radiation by Toll-like receptors. The search for new immunoenhancers and agents for relieving immunosuppression is of great importance to immune construction for radiation sickness. (authors)

Manipulating adenovirus hexon hypervariable loops dictates immune neutralisation and coagulation factor X-dependent cell interaction in vitro and in vivo.

Directory of Open Access Journals (Sweden)

Jiangtao Ma

2015-02-01

Full Text Available Adenoviruses are common pathogens, mostly targeting ocular, gastrointestinal and respiratory cells, but in some cases infection disseminates, presenting in severe clinical outcomes. Upon dissemination and contact with blood, coagulation factor X (FX interacts directly with the adenovirus type 5 (Ad5 hexon. FX can act as a bridge to bind heparan sulphate proteoglycans, leading to substantial Ad5 hepatocyte uptake. FX "coating" also protects the virus from host IgM and complement-mediated neutralisation. However, the contribution of FX in determining Ad liver transduction whilst simultaneously shielding the virus from immune attack remains unclear. In this study, we demonstrate that the FX protection mechanism is not conserved amongst Ad types, and identify the hexon hypervariable regions (HVR of Ad5 as the capsid proteins targeted by this host defense pathway. Using genetic and pharmacological approaches, we manipulate Ad5 HVR interactions to interrogate the interplay between viral cell transduction and immune neutralisation. We show that FX and inhibitory serum components can co-compete and virus neutralisation is influenced by both the location and extent of modifications to the Ad5 HVRs. We engineered Ad5-derived HVRs into the rare, native non FX-binding Ad26 to create Ad26.HVR5C. This enabled the virus to interact with FX at high affinity, as quantified by surface plasmon resonance, FX-mediated cell binding and transduction assays. Concomitantly, Ad26.HVR5C was also sensitised to immune attack in the absence of FX, a direct consequence of the engineered HVRs from Ad5. In both immune competent and deficient animals, Ad26.HVR5C hepatic gene transfer was mediated by FX following intravenous delivery. This study gives mechanistic insight into the pivotal role of the Ad5 HVRs in conferring sensitivity to virus neutralisation by IgM and classical complement-mediated attack. Furthermore, through this gain-of-function approach we demonstrate the dual

Relations between immune and mediator receptors of mouse lymphocytes

International Nuclear Information System (INIS)

Ado, A.D.; Alekseeva, T.A.; Kravchenko, S.A.

1985-01-01

This paper examines the action of the specific muscarinic antogonist tritium-quinuclidinyl benzilate (tritium-QNB) on immune rosette formation in mice. It is shown that since the specific muscarini antagonist tritium-QNB inhibits immune rosette formation, this process must be regarded as interconnected with muscarinic receptors of lymphocytes. Interaction of immune (antigen-binding) and mediator receptors, however, is an important factor maintaining immune homeostasis at a certain level

Modulation of host immunity by tick saliva

Czech Academy of Sciences Publication Activity Database

Kotál, Jan; Langhansová, H.; Lieskovská, J.; Andersen, J. F.; Francischetti, I.M.B.; Chavakis, T.; Kopecký, J.; Pedra, J. H. F.; Kotsyfakis, Michalis; Chmelař, J.

2015-01-01

Roč. 128, OCT 14 2015 (2015), s. 58-68 ISSN 1874-3919 R&D Projects: GA ČR GAP502/12/2409 Institutional support: RVO:60077344 Keywords : Adaptive immunity * Innate immunity * Saliva * Salivary glands * Tick Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.867, year: 2015

Immune defense and host life history.

Science.gov (United States)

Zuk, Marlene; Stoehr, Andrew M

2002-10-01

Recent interest has focused on immune response in an evolutionary context, with particular attention to disease resistance as a life-history trait, subject to trade-offs against other traits such as reproductive effort. Immune defense has several characteristics that complicate this approach, however; for example, because of the risk of autoimmunity, optimal immune defense is not necessarily maximum immune defense. Two important types of cost associated with immunity in the context of life history are resource costs, those related to the allocation of essential but limited resources, such as energy or nutrients, and option costs, those paid not in the currency of resources but in functional or structural components of the organism. Resource and option costs are likely to apply to different aspects of resistance. Recent investigations into possible trade-offs between reproductive effort, particularly sexual displays, and immunity have suggested interesting functional links between the two. Although all organisms balance the costs of immune defense against the requirements of reproduction, this balance works out differently for males than it does for females, creating sex differences in immune response that in turn are related to ecological factors such as the mating system. We conclude that immune response is indeed costly and that future work would do well to include invertebrates, which have sometimes been neglected in studies of the ecology of immune defense.

Analysis of receptor signaling pathways by mass spectrometry: identification of vav-2 as a substrate of the epidermal and platelet-derived growth factor receptors

DEFF Research Database (Denmark)

Pandey, A; Podtelejnikov, A V; Blagoev, B

2000-01-01

Oligomerization of receptor protein tyrosine kinases such as the epidermal growth factor receptor (EGFR) by their cognate ligands leads to activation of the receptor. Transphosphorylation of the receptor subunits is followed by the recruitment of signaling molecules containing src homology 2 (SH2...

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

Science.gov (United States)

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

2012-02-07

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 apoptosis, leading to the depletion of DC populations, especially the CD8(+) and CD103(+) DC subsets in lymphoid and nonlymphoid tissues, respectively. TAK1 also contributed to DC development by promoting the generation of DC precursors. Prosurvival signals from Toll-like receptors, CD40 and receptor activator of nuclear factor-κB (RANK) are integrated by TAK1 in DCs, which in turn mediated activation of downstream NF-κB and AKT-Foxo pathways and established a gene-expression program. TAK1 deficiency in DCs caused a myeloid proliferative disorder characterized by expansion of neutrophils and inflammatory monocytes, disrupted T-cell homeostasis, and prevented effective T-cell priming and generation of regulatory T cells. Moreover, TAK1 signaling in DCs was required to prevent myeloid proliferation even in the absence of lymphocytes, indicating a previously unappreciated regulatory mechanism of DC-mediated control of myeloid cell-dependent inflammation. Therefore, TAK1 orchestrates a prosurvival checkpoint in DCs that affects the homeostasis and function of the immune system.

PPARγ Agonists in Adaptive Immunity: What Do Immune Disorders and Their Models Have to Tell Us?

Directory of Open Access Journals (Sweden)

Laurindo Ferreira da Rocha Junior

2013-01-01

Full Text Available Adaptive immunity has evolved as a very powerful and highly specialized tool of host defense. Its classical protagonists are lymphocytes of the T- and B-cell lineage. Cytokines and chemokines play a key role as effector mechanisms of the adaptive immunity. Some autoimmune and inflammatory diseases are caused by disturbance of the adaptive immune system. Recent advances in understanding the pathogenesis of autoimmune diseases have led to research on new molecular and therapeutic targets. PPARγ are members of the nuclear receptor superfamily and are transcription factors involved in lipid metabolism as well as innate and adaptive immunity. PPARγ is activated by synthetic and endogenous ligands. Previous studies have shown that PPAR agonists regulate T-cell survival, activation and T helper cell differentiation into effector subsets: Th1, Th2, Th17, and Tregs. PPARγ has also been associated with B cells. The present review addresses these issues by placing PPARγ agonists in the context of adaptive immune responses and the relation of the activation of these receptors with the expression of cytokines involved in adaptive immunity.

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

OpenAIRE

Nurmasitoh, Titis

2015-01-01

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

Tumor necrosis factor (TNF) receptor shedding controls thresholds of innate immune activation that balance opposing TNF functions in infectious and inflammatory diseases

DEFF Research Database (Denmark)

Xanthoulea, Sofia; Pasparakis, Manolis; Kousteni, Stavroula

2004-01-01

Tumor necrosis factor (TNF) is a potent cytokine exerting critical functions in the activation and regulation of immune and inflammatory responses. Due to its pleiotropic activities, the amplitude and duration of TNF function must be tightly regulated. One of the mechanisms that may have evolved...... to modulate TNF function is the proteolytic cleavage of its cell surface receptors. In humans, mutations affecting shedding of the p55TNF receptor (R) have been linked with the development of the TNFR-associated periodic syndromes, disorders characterized by recurrent fever attacks and localized inflammation....... Here we show that knock-in mice expressing a mutated nonsheddable p55TNFR develop Toll-like receptor-dependent innate immune hyperreactivity, which renders their immune system more efficient at controlling intracellular bacterial infections. Notably, gain of function for antibacterial host defenses...

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

Directory of Open Access Journals (Sweden)

Xiao-Bin Peng

2016-10-01

Full Text Available 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 6 h and postoperative 24 h. 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 6 h, 24 h serum amylase were significantly higher than before surgery; in the observation group, the postoperative 6 h, 24 h 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 6 h, 24 h serum proinflammatory factor IL-6 and TNF-α increased first and then decreased, both were significantly higher than before surgery; both two groups’ postoperative 6 h, 24 h 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, antiinflammatory 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 6 h and 24 h after surgery, the difference between the two groups was statistically significant (P<0.05. Both two groups’ postoperative 6 h, 24 h T cell subsets CD3+ , CD4+ , CD4

Reducing child mortality in Nigeria: a case study of immunization and systemic factors.

Science.gov (United States)

Nwogu, Rufus; Ngowu, Rufus; Larson, James S; Kim, Min Su

2008-07-01

The purpose of the study is to assess the outcome of the Expanded Program on Immunization (EPI) in Nigeria, as well as to examine systemic factors influencing its high under-five mortality rate (UFMR). The principal objective of the EPI program when it was implemented in 1978 was to reduce mortality, morbidity and disability associated with six vaccine preventable diseases namely tuberculosis, tetanus, diphtheria, measles, pertussis and poliomyelitis. The methodological approach to this study is quantitative, using secondary time series data from 1970 to 2003. The study tested three hypotheses using time series multiple regression analysis with autocorrelation adjustment as a statistical model. The results showed that the EPI program had little effect on UFMR in Nigeria. Only the literacy rate and domestic spending on healthcare had statistically significant effects on the UFMR. The military government was not a significant factor in reducing or increasing the UFMR. It appears that Nigeria needs a unified approach to healthcare delivery, rather than fragmented programs, to overcome cultural and political divisions in society.

Tick Innate Immunity.

Czech Academy of Sciences Publication Activity Database

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

2010-01-01

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

Prenatal Alcohol Exposure and the Developing Immune System.

Science.gov (United States)

Gauthier, Theresa W

2015-01-01

Evidence from research in humans and animals suggest that ingesting alcohol during pregnancy can disrupt the fetal immune system and result in an increased risk of infections and disease in newborns that may persist throughout life. Alcohol may have indirect effects on the immune system by increasing the risk of premature birth, which itself is a risk factor for immune-related problems. Animal studies suggest that alcohol exposure directly disrupts the developing immune system. A comprehensive knowledge of the mechanisms underlying alcohol's effects on the developing immune system only will become clear once researchers establish improved methods for identifying newborns exposed to alcohol in utero.

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.

Regulatory immune cells and functions in autoimmunity and transplantation immunology.

Science.gov (United States)

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

2017-05-01

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

Evolution of transgenerational immunity in invertebrates.

Science.gov (United States)

Pigeault, R; Garnier, R; Rivero, A; Gandon, S

2016-09-28

Over a decade ago, the discovery of transgenerational immunity in invertebrates shifted existing paradigms on the lack of sophistication of their immune system. Nonetheless, the prevalence of this trait and the ecological factors driving its evolution in invertebrates remain poorly understood. Here, we develop a theoretical host-parasite model and predict that long lifespan and low dispersal should promote the evolution of transgenerational immunity. We also predict that in species that produce both philopatric and dispersing individuals, it may pay to have a plastic allocation strategy with a higher transgenerational immunity investment in philopatric offspring because they are more likely to encounter locally adapted pathogens. We review all experimental studies published to date, comprising 21 invertebrate species in nine different orders, and we show that, as expected, longevity and dispersal correlate with the transfer of immunity to offspring. The validity of our prediction regarding the plasticity of investment in transgenerational immunity remains to be tested in invertebrates, but also in vertebrate species. We discuss the implications of our work for the study of the evolution of immunity, and we suggest further avenues of research to expand our knowledge of the impact of transgenerational immune protection in host-parasite interactions. © 2016 The Author(s).

Immune escape strategies of malaria parasites

Directory of Open Access Journals (Sweden)

Pollyanna Stephanie Gomes

2016-10-01

Full Text Available Malaria is one of the most life-threatening infectious diseases worldwide. Immunity to malaria is slow and short-lived despite the repeated parasite exposure in endemic areas. Malaria parasites have evolved refined machinery to evade the immune system based on a range of genetic changes that include allelic variation, biomolecular exposure of proteins and intracellular replication. All of these features increase the probability of survival in both mosquitoes and the vertebrate host. Plasmodium species escape from the first immunological trap in its invertebrate vector host, the Anopheles mosquitoes. The parasites have to pass through various immunological barriers within the mosquito such as anti-microbial molecules and the mosquito microbiota in order to achieve successful transmission to the vertebrate host. Within these hosts, Plasmodium species employ various immune evasion strategies during different life cycle stages. Parasite persistence against the vertebrate immune response depends on the balance among virulence factors, pathology, metabolic cost of the host immune response, and the parasites ability to evade the immune response. In this review we discuss the strategies that Plasmodium parasites use to avoid the vertebrate host immune system and how they promote successful infection and transmission.

Nutritional strategies to optimize dairy cattle immunity.

Science.gov (United States)

Sordillo, L M

2016-06-01

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

A Common Structural Motif in the Binding of Virulence Factors to Bacterial Secretion Chaperones

International Nuclear Information System (INIS)

Lilic, M.; Vujanac, M.; Stebbins, C.

2006-01-01

Salmonella invasion protein A (SipA) is translocated into host cells by a type III secretion system (T3SS) and comprises two regions: one domain binds its cognate type III secretion chaperone, InvB, in the bacterium to facilitate translocation, while a second domain functions in the host cell, contributing to bacterial uptake by polymerizing actin. We present here the crystal structures of the SipA chaperone binding domain (CBD) alone and in complex with InvB. The SipA CBD is found to consist of a nonglobular polypeptide as well as a large globular domain, both of which are necessary for binding to InvB. We also identify a structural motif that may direct virulence factors to their cognate chaperones in a diverse range of pathogenic bacteria. Disruption of this structural motif leads to a destabilization of several chaperone-substrate complexes from different species, as well as an impairment of secretion in Salmonella

Galectin-1 influences trophoblast immune evasion and emerges as a predictive factor for the outcome of pregnancy.

Science.gov (United States)

Tirado-González, Irene; Freitag, Nancy; Barrientos, Gabriela; Shaikly, Valerie; Nagaeva, Olga; Strand, Magnus; Kjellberg, Lennart; Klapp, Burghard F; Mincheva-Nilsson, Lucia; Cohen, Marie; Blois, Sandra M

2013-01-01

Galectin-1 (gal-1) is expressed at the feto-maternal interface and plays a role in regulating the maternal immune response against placental alloantigens, contributing to pregnancy maintenance. Both decidua and placenta contribute to gal-1 expression and may be important for the maternal immune regulation. The expression of gal-1 within the placenta is considered relevant to cell-adhesion and invasion of trophoblasts, but the role of gal-1 in the immune evasion machinery exhibited by trophoblast cells remains to be elucidated. In this study, we analyzed gal-1 expression in preimplantation human embryos and first-trimester decidua-placenta specimens and serum gal-1 levels to investigate the physiological role played by this lectin during pregnancy. The effect on human leukocyte antigen G (HLA-G) expression in response to stimulation or silencing of gal-1 was also determined in the human invasive, proliferative extravillous cytotrophoblast 65 (HIPEC65) cell line. Compared with normal pregnant women, circulating gal-1 levels were significantly decreased in patients who subsequently suffered a miscarriage. Human embryos undergoing preimplantation development expressed gal-1 on the trophectoderm and inner cell mass. Furthermore, our in vitro experiments showed that exogenous gal-1 positively regulated the membrane-bound HLA-G isoforms (HLA-G1 and G2) in HIPEC65 cells, whereas endogenous gal-1 also induced expression of the soluble isoforms (HLA-G5 and -G6). Our results suggest that gal-1 plays a key role in pregnancy maternal immune regulation by modulating HLA-G expression on trophoblast cells. Circulating gal-1 levels could serve as a predictive factor for pregnancy success in early human gestation.

Immunity to sporozoite-induced malaria infection in mice. I. The effect of immunization of T and B cell-deficient mice

International Nuclear Information System (INIS)

Chen, D.H.; Tigelaar, R.E.; Weinbaum, F.I.

1977-01-01

The cellular basis of immunity to sporozoites was investigated by examining the effect of immunization of T and B cell-deficient C57BL/6N x BALB/c AnN F 1 (BLCF 1 ) mice compared to immunocompetent controls. Immunization of T cell-deficient (ATX-BM-ATS) BLCF 1 mice with x-irradiated sporozoites did not result in the generation of protective immunity. The same immunization protocols protected all immunocompetent controls. In contrast, B cell-deficient (μ-suppressed) BLCF 1 mice were protected by immunization in the majority of cases. The absence of detectable serum circumsporozoite precipitins or sporozoite neutralizing activity in the μ-suppressed mice that resisted a sporozoite challenge suggests a minor role for these humoral factors in protection. These data demonstrate a preeminent role for T cells in the induction of protective immunity in BLCF 1 mice against a P. berghei sporozoite infection

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.

The Role of the Immune System Beyond the Fight Against Infection.

Science.gov (United States)

Sattler, Susanne

2017-01-01

The immune system was identified as a protective factor during infectious diseases over a century ago. Current definitions and textbook information are still largely influenced by these early observations, and the immune system is commonly presented as a defence machinery. However, host defence is only one manifestation of the immune system's overall function in the maintenance of tissue homeostasis and system integrity. In fact, the immune system is integral part of fundamental physiological processes such as development, reproduction and wound healing, and a close crosstalk between the immune system and other body systems such as metabolism, the central nervous system and the cardiovascular system is evident. Research and medical professionals in an expanding range of areas start to recognise the implications of the immune system in their respective fields.This chapter provides a brief historical perspective on how our understanding of the immune system has evolved from a defence system to an overarching surveillance machinery to maintain tissue integrity. Current perspectives on the non-defence functions of classical immune cells and factors will also be discussed.

Regional specialization within the intestinal immune system

DEFF Research Database (Denmark)

Mowat, Allan M.; Agace, William Winston

2014-01-01

The intestine represents the largest compartment of the immune system. It is continually exposed to antigens and immunomodulatory agents from the diet and the commensal microbiota, and it is the port of entry for many clinically important pathogens. Intestinal immune processes are also increasingly...... implicated in controlling disease development elsewhere in the body. In this Review, we detail the anatomical and physiological distinctions that are observed in the small and large intestines, and we suggest how these may account for the diversity in the immune apparatus that is seen throughout...... the intestine. We describe how the distribution of innate, adaptive and innate-like immune cells varies in different segments of the intestine and discuss the environmental factors that may influence this. Finally, we consider the implications of regional immune specialization for inflammatory disease...

Binding of properdin to solid-phase immune complexes

DEFF Research Database (Denmark)

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

1998-01-01

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

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

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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.

Integration of the immune system: a complex adaptive supersystem

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Crisman, Mark V.

2001-10-01

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

Human intestinal dendritic cells as controllers of mucosal immunity

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David Bernardo

2013-06-01

Full Text Available Dendritic cells are the most potent, professional antigen-presenting cells in the body; following antigen presentation they control the type (proinflammatory/regulatory of immune response that will take place, as well as its location. Given their high plasticity and maturation ability in response to local danger signals derived from innate immunity, dendritic cells are key actors in the connection between innate immunity and adaptive immunity responses. In the gut dendritic cells control immune tolerance mechanisms against food and/or commensal flora antigens, and are also capable of initiating an active immune response in the presence of invading pathogens. Dendritic cells are thus highly efficient in controlling the delicate balance between tolerance and immunity in an environment so rich in antigens as the gut, and any factor involving these cells may impact their function, ultimately leading to the development of bowel conditions such as celiac disease or inflammatory bowel disease. In this review we shall summarize our understanding of human intestinal dendritic cells, their ability to express and induce migration markers, the various environmental factors modulating their properties, their subsets in the gut, and the problems entailed by their study, including identification strategies, differences between humans and murine models, and phenotypical variations along the gastrointestinal tract.

The Tomato U-Box Type E3 Ligase PUB13 Acts With Group III Ubiquitin E2 Enzymes to Modulate FLS2-Mediated Immune Signaling

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Bangjun Zhou

2018-05-01

Full Text Available In Arabidopsis and rice, the ubiquitin ligase PUB13-mediated protein degradation plays a significant role in plant pattern-triggered immunity (PTI and flowering time control. The Arabidopsis PUB13 has been shown to attenuate the pattern recognition receptor FLS2-mediated immune signaling by ubiquitinating FLS2 and consequently promoting its degradation by the 26S proteasome. Nevertheless, the cognate ubiquitin-conjugating enzymes (E2 with which PUB13 acts to modulate FLS2-mediated PTI are unknown. To address this question, we investigate here the tomato (Solanum lycopersicum homolog of PUB13, SlPUB13 by utilizing the recently characterized complete set of tomato E2s. Of the 13 groups of tomato E2s, only members in group III are found to interact and act with SlPUB13. Knocking-down of the group III E2 genes enhances callose deposition and induction of the RbohB gene in the immunity-associated, early oxidative burst after flg22 treatment. The group III E2s are also found to work with SlPUB13 to ubiquitinate FLS2 in vitro and are required for PUB13-mediated degradation of FLS2 in vivo upon flg22 treatment, suggesting an essential role for group III E2s in the modulation of FLS2-mediated immune signaling by PUB13. Additionally, another immunity-associated E3, NtCMPG1 is shown to also work specifically with members of group III E2 in the in vitro ubiquitination assay, which implies the group III E2 enzymes may cooperate with many E3 ligases to regulate different aspects of PTI. Taken together, these data corroborate the notion that group III E2 enzymes play an important role in PTI and build a foundation for further functional and mechanistic characterization of tomato PUB13.

Tumor Necrosis Factor-α Is Required for Mast Cell-Mediated Host Immunity Against Cutaneous Staphylococcus aureus Infection.

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Liu, Chao; Ouyang, Wei; Xia, Jingyan; Sun, Xiaoru; Zhao, Liying; Xu, Feng

2018-05-08

Mast cells (MCs) play a key role in immune process response to invading pathogens. This study assessed the involvement of MCs in controlling Staphylococcus aureus infection in a cutaneous infection model of MC-deficient (KitW-sh/W-sh) mice. KitW-sh/W-sh mice developed significantly larger skin lesions after the cutaneous S. aureus challenge, when compared to wild-type (WT) mice, while MC dysfunction reduced the inflammation response to S. aureus. The levels of tumor necrosis factor (TNF)-α in skin tissues were significantly decreased in KitW-sh/W-sh mice upon infection. Moreover, the exogenous administration of MCs or recombinant TNF-α effectively restored the immune response against S. aureus in KitW-sh/W-sh mice via the recruitment of neutrophils to the infected site. These results indicate that the effects of MC deficiency are largely attributed to the decrease in production of TNF-α in cutaneous S. aureus infection. In addition, S. aureus-induced MC activation was dependent on the c-kit receptor-activated phosphoinositide 3-kinase (PI3K)/AKT/P65-nuclear factor (NF-κB) pathway, which was confirmed by treatment with Masitinib (a c-kit receptor inhibitor), Wortmannin (a PI3K inhibitor), and pyrrolidine dithiocarbamate (a NF-κB inhibitor), respectively. The present study identifies the critical role of MCs in the host defense against S. aureus infection.

Interactions of commensal gut microbes with subsets of B- and T-cells in the murine host

NARCIS (Netherlands)

Jiang, HQ; Thurnheer, MC; Zuercher, AW; Boiko, NV; Bos, NA; Cebra, JJ

2004-01-01

Although mechanisms operative in the induction and maintenance of specific, adaptive immunity, including 'cognate' B/T interactions, have been extensively studied and defined, we still know little about the mechanisms operative in developing and maintaining B- and T-cell dependent 'natural'

Modulation of immune homeostasis by commensal bacteria

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Ivanov, Ivaylo I.; Littman, Dan R.

2011-01-01

Intestinal bacteria form a resident community that has co-evolved with the mammalian host. In addition to playing important roles in digestion and harvesting energy, commensal bacteria are crucial for the proper functioning of mucosal immune defenses. Most of these functions have been attributed to the presence of large numbers of “innocuous” resident bacteria that dilute or occupy niches for intestinal pathogens or induce innate immune responses that sequester bacteria in the lumen, thus quenching excessive activation of the mucosal immune system. However it has recently become obvious that commensal bacteria are not simply beneficial bystanders, but are important modulators of intestinal immune homeostasis and that the composition of the microbiota is a major factor in pre-determining the type and robustness of mucosal immune responses. Here we review specific examples of individual members of the microbiota that modify innate and adaptive immune responses, and we focus on potential mechanisms by which such species-specific signals are generated and transmitted to the host immune system. PMID:21215684

Necroptotic signaling in adaptive and innate immunity.

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Lu, Jennifer V; Chen, Helen C; Walsh, Craig M

2014-11-01

The vertebrate immune system is highly dependent on cell death for efficient responsiveness to microbial pathogens and oncogenically transformed cells. Cell death pathways are vital to the function of many immune cell types during innate, humoral and cellular immune responses. In addition, cell death regulation is imperative for proper adaptive immune self-tolerance and homeostasis. While apoptosis has been found to be involved in several of these roles in immunity, recent data demonstrate that alternative cell death pathways are required. Here, we describe the involvement of a programmed form of cellular necrosis called "necroptosis" in immunity. We consider the signaling pathways that promote necroptosis downstream of death receptors, type I transmembrane proteins of the tumor necrosis factor (TNF) receptor family. The involvement of necroptotic signaling through a "RIPoptosome" assembled in response to innate immune stimuli or genotoxic stress is described. We also characterize the induction of necroptosis following antigenic stimulation in T cells lacking caspase-8 or FADD function. While necroptotic signaling remains poorly understood, it is clear that this pathway is an essential component to effective vertebrate immunity. Copyright © 2014 Elsevier Ltd. All rights reserved.

What’s Normal? Immune Profiling of Human Milk from Healthy Women Living in Different Geographical and Socioeconomic Settings

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Ruiz, Lorena; Espinosa-Martos, Irene; García-Carral, Cristina; Manzano, Susana; McGuire, Michelle K.; Meehan, Courtney L.; McGuire, Mark A.; Williams, Janet E.; Foster, James; Sellen, Daniel W.; Kamau-Mbuthia, Elizabeth W.; Kamundia, Egidioh W.; Mbugua, Samwel; Moore, Sophie E.; Kvist, Linda J.; Otoo, Gloria E.; Lackey, Kimberly A.; Flores, Katherine; Pareja, Rossina G.; Bode, Lars; Rodríguez, Juan M.

2017-01-01

Human milk provides a very wide range of nutrients and bioactive components, including immune factors, human milk oligosaccharides, and a commensal microbiota. These factors are essential for interconnected processes including immunity programming and the development of a normal infant gastrointestinal microbiome. Newborn immune protection mostly relies on maternal immune factors provided through milk. However, studies dealing with an in-depth profiling of the different immune compounds present in human milk and with the assessment of their natural variation in healthy women from different populations are scarce. In this context, the objective of this work was the detection and quantification of a wide array of immune compounds, including innate immunity factors (IL1β, IL6, IL12, INFγ, TNFα), acquired immunity factors (IL2, IL4, IL10, IL13, IL17), chemokines (IL8, Groα, MCP1, MIP1β), growth factors [IL5, IL7, epidermal growth factor (EGF), granulocyte colony-stimulating factor, granulocyte–macrophage colony-stimulating factor, TGFβ2], and immunoglobulins (IgA, IgG, IgM), in milk produced by healthy women of different ethnicities living in different geographic, dietary, socioeconomic, and environmental settings. Among the analyzed factors, IgA, IgG, IgM, EGF, TGFβ2, IL7, IL8, Groα, and MIP1β were detected in all or most of the samples collected in each population and, therefore, this specific set of compounds might be considered as the “core” soluble immune factors in milk produced by healthy women worldwide. This approach may help define which immune factors are (or are not) common in milk produced by women living in various conditions, and to identify host, lifestyle, and environmental factors that affect the immunological composition of this complex biological fluid. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02670278. PMID:28713365

What’s Normal? Immune Profiling of Human Milk from Healthy Women Living in Different Geographical and Socioeconomic Settings

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Lorena Ruiz

2017-06-01

Full Text Available Human milk provides a very wide range of nutrients and bioactive components, including immune factors, human milk oligosaccharides, and a commensal microbiota. These factors are essential for interconnected processes including immunity programming and the development of a normal infant gastrointestinal microbiome. Newborn immune protection mostly relies on maternal immune factors provided through milk. However, studies dealing with an in-depth profiling of the different immune compounds present in human milk and with the assessment of their natural variation in healthy women from different populations are scarce. In this context, the objective of this work was the detection and quantification of a wide array of immune compounds, including innate immunity factors (IL1β, IL6, IL12, INFγ, TNFα, acquired immunity factors (IL2, IL4, IL10, IL13, IL17, chemokines (IL8, Groα, MCP1, MIP1β, growth factors [IL5, IL7, epidermal growth factor (EGF, granulocyte colony-stimulating factor, granulocyte–macrophage colony-stimulating factor, TGFβ2], and immunoglobulins (IgA, IgG, IgM, in milk produced by healthy women of different ethnicities living in different geographic, dietary, socioeconomic, and environmental settings. Among the analyzed factors, IgA, IgG, IgM, EGF, TGFβ2, IL7, IL8, Groα, and MIP1β were detected in all or most of the samples collected in each population and, therefore, this specific set of compounds might be considered as the “core” soluble immune factors in milk produced by healthy women worldwide. This approach may help define which immune factors are (or are not common in milk produced by women living in various conditions, and to identify host, lifestyle, and environmental factors that affect the immunological composition of this complex biological fluid.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT02670278.

Relationships between caused by drinking of bioactive water Naftussya changes in urine lithogenicity and neuro-humoral-immune factors in humans with theirs abnormalities

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Victor R. Flyunt

2017-01-01

Full Text Available Objective. Spa Truskavets' (Ukraine considered to be indicated for the treatment and metaphylaxis renal stone disease. However, data on the effect of balneotherapy on the parameters of urine Lithogenicity ambiguous. This is due, perhaps, ambiguous influence balneotherapy on the neuroendocrine factors regulating exchange of electrolytes and uric acid. Aim: to find out the influence drinking of bioactive water Naftussya on urine lithogenicity and neuro-humoral-immune factors in humans with theirs abnormalities. Methods. The object of observation were ten women and ten men aged 33-76 years without clinical diagnose but with dysfunction of neuro-endocrine-immune complex and metabolism. In daily urine and blood we determined the content of electrolytes and nitrogenous metabolites, estimated parameters of immunity, recorded conductivity of acupuncture points and heart rate variability (HRV. After examination volunteers within 7 days used bioactive water Naftussya (250 ml three times a day, then repeated the tests listed. Results. Lithogenicity urine Index (Lith calculated by formula: Lith=(Uric acid•Calcium/Magnesium•Creatinine0,25. In 3 people initial normal Lith (0,65÷0,81 units increased by 0,08÷0,16 units. In 4 people with normal or high Lith its changes were not detected (-0,01÷+0,01. In 12 people from a wide range of primary Lith (0,62÷1,07 it lowered by 0,03÷0,12 un. Even in a man maximum level of Lith (1,45 un. down to the upper limit of normal (0,84 un.. Found a strong correlation between changes in Lith and a number parameters of HRV, metabolism and immunity. Conclusion. The use of bioactive water Naftussya causes ambiguous changes in Lithogenicity of urine, related to ambiguous changes in HRV, metabolism and immunity.

Infant Sleep After Immunization: Randomized Controlled Trial of Prophylactic Acetaminophen

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Gay, Caryl L.; Lynch, Mary; Lee, Kathryn A.

2011-01-01

OBJECTIVE: To determine the effects of acetaminophen and axillary temperature responses on infant sleep duration after immunization. METHODS: We conducted a prospective, randomized controlled trial to compare the sleep of 70 infants monitored by using ankle actigraphy for 24 hours before and after their first immunization series at ∼2 months of age. Mothers of infants in the control group received standard care instructions from their infants' health care provider, and mothers of infants in the intervention group were provided with predosed acetaminophen and instructed to administer a dose 30 minutes before the scheduled immunization and every 4 hours thereafter, for a total of 5 doses. Infant age and birth weight and immunization factors, such as acetaminophen use and timing of administration, were evaluated for changes in infant sleep times after immunization. RESULTS: Sleep duration in the first 24 hours after immunization was increased, particularly for infants who received their immunizations after 1:30 pm and for those who experienced elevated temperatures in response to the vaccines. Infants who received acetaminophen at or after immunization had smaller increases in sleep duration than did infants who did not. However, acetaminophen use was not a significant predictor of sleep duration when other factors were controlled. CONCLUSIONS: If further research confirms the relationship between time of day of vaccine administration, increased sleep duration after immunization, and antibody responses, then our findings suggest that afternoon immunizations should be recommended to facilitate increased sleep in the 24 hours after immunization, regardless of acetaminophen administration. PMID:22123869

Influence of Physical Activity and Nutrition on Obesity-Related Immune Function

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Chun-Jung Huang

2013-01-01

Full Text Available Research examining immune function during obesity suggests that excessive adiposity is linked to impaired immune responses leading to pathology. The deleterious effects of obesity on immunity have been associated with the systemic proinflammatory profile generated by the secretory molecules derived from adipose cells. These include inflammatory peptides, such as TNF-α, CRP, and IL-6. Consequently, obesity is now characterized as a state of chronic low-grade systemic inflammation, a condition considerably linked to the development of comorbidity. Given the critical role of adipose tissue in the inflammatory process, especially in obese individuals, it becomes an important clinical objective to identify lifestyle factors that may affect the obesity-immune system relationship. For instance, stress, physical activity, and nutrition have each shown to be a significant lifestyle factor influencing the inflammatory profile associated with the state of obesity. Therefore, the purpose of this review is to comprehensively evaluate the impact of lifestyle factors, in particular psychological stress, physical activity, and nutrition, on obesity-related immune function with specific focus on inflammation.

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.

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......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......, 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...

Passive Immunization with Milk Produced from an Immunized Cow Prevents Oral Recolonization by Streptococcus mutans

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Shimazaki, Yoshihiro; Mitoma, Morihide; Oho, Takahiko; Nakano, Yoshio; Yamashita, Yoshihisa; Okano, Kaoru; Nakano, Yutaka; Fukuyama, Masataka; Fujihara, Noboru; Nada, Youichi; Koga, Toshihiko

2001-01-01

Cell surface protein antigen (PAc) and water-insoluble glucan-synthesizing enzyme (GTF-I) produced by cariogenic Streptococcus mutans are two major factors implicated in the colonization of the human oral cavity by this bacterium. We examined the effect of bovine milk, produced after immunization with a fusion protein of functional domains of these proteins, on the recolonization of S. mutans. To prepare immune milk, a pregnant Holstein cow was immunized with the fusion protein PAcA-GB, a fusion of the saliva-binding alanine-rich region (PAcA) of PAc and the glucan-binding (GB) domain of GTF-I. After eight adult subjects received cetylpyridinium chloride (CPC) treatment, one subgroup (n = 4) rinsed their mouths with immune milk and a control group (n = 4) rinsed with nonimmune milk. S. mutans levels in saliva and dental plaque decreased after CPC treatment in both groups. Mouth rinsing with immune milk significantly inhibited recolonization of S. mutans in saliva and plaque. On the other hand, the numbers of S. mutans cells in saliva and plaque in the control group increased immediately after the CPC treatment and surpassed the baseline level 42 and 28 days, respectively, after the CPC treatment. The ratios of S. mutans to total streptococci in saliva and plaque in the group that received immune milk were lower than those in the control group. These results suggest that milk produced from immunized cow may be useful for controlling S. mutans in the human oral cavity. PMID:11687453

Exploring the Causes of Low Immunization Status in School Going Children

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Madhuri Inamdar

2012-01-01

Full Text Available Background: Although a definitive immunization program has been advocated for children in our country, the immunization coverage is far from satisfactory. There is paucity of survey studies related to immunization pattern. Objective: This study has been undertaken to explore the social and attitudinal factors with parents resulting into adverse immunization. Material and Methods: The study was school based cross-sectional study conducted in 50 schools of Indore district selected by random sampling from three groups. Information was collected from parents by providing pre-tested questionnaire. Result: Association of parent’s literacy and socioeconomic status with successful immunization could be established. Overall coverage rate with vaccines was poor in school going girls as compared to the boys; proving thereby that gender discrimination exists putting girls in disadvantageous position. Conclusion: It can be expected that the immunization status of school children will improve if identified risk factors such as parental education, socioeconomic status, awareness status are improved and attitudinal gender discrimination is curbed.

Lymphoma: Immune Evasion Strategies

International Nuclear Information System (INIS)

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

2015-01-01

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

Lymphoma: Immune Evasion Strategies

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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.

Missed Opportunities For Immunization In Children And Pregnant Women

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Benjamin A I

1990-01-01

Full Text Available The role of immunization in reducing childhood mortality cannot be over-emphasised, yet many opportunities for immunization are missed when children and pregnant women visit a health facility. Reducing missed opportunities is the cheapest way to increase immunization coverage. The present study discusses the extent of the problem of missed opportunities for immunization in children and pregnant women and the factors contributing to the problem, in spatiality and community outreach clinics of Christian Medical College & Hospital, Ludhiana. Recommendations are made regarding ways and means of reducing missed opportunities.

Role of the Immune System in Hypertension.

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Rodriguez-Iturbe, Bernardo; Pons, Hector; Johnson, Richard J

2017-07-01

High blood pressure is present in more than one billion adults worldwide and is the most important modifiable risk factor of death resulting from cardiovascular disease. While many factors contribute to the pathogenesis of hypertension, a role of the immune system has been firmly established by a large number of investigations from many laboratories around the world. Immunosuppressive drugs and inhibition of individual cytokines prevent or ameliorate experimental hypertension, and studies in genetically-modified mouse strains have demonstrated that lymphocytes are necessary participants in the development of hypertension and in hypertensive organ injury. Furthermore, immune reactivity may be the driving force of hypertension in autoimmune diseases. Infiltration of immune cells, oxidative stress, and stimulation of the intrarenal angiotensin system are induced by activation of the innate and adaptive immunity. High blood pressure results from the combined effects of inflammation-induced impairment in the pressure natriuresis relationship, dysfunctional vascular relaxation, and overactivity of the sympathetic nervous system. Imbalances between proinflammatory effector responses and anti-inflammatory responses of regulatory T cells to a large extent determine the severity of inflammation. Experimental and human studies have uncovered autoantigens (isoketal-modified proteins and heat shock protein 70) of potential clinical relevance. Further investigations on the immune reactivity in hypertension may result in the identification of new strategies for the treatment of the disease. Copyright © 2017 the American Physiological Society.

Leishmania Hijacks Myeloid Cells for Immune Escape

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María Martínez-López

2018-05-01

Full Text Available Protozoan parasites of the Leishmania genus are the causative agents of leishmaniasis, a group of neglected tropical diseases whose clinical manifestations vary depending on the infectious Leishmania species but also on host factors. Recognition of the parasite by host myeloid immune cells is a key to trigger an effective Leishmania-specific immunity. However, the parasite is able to persist in host myeloid cells by evading, delaying and manipulating host immunity in order to escape host resistance and ensure its transmission. Neutrophils are first in infiltrating infection sites and could act either favoring or protecting against infection, depending on factors such as the genetic background of the host or the parasite species. Macrophages are the main host cells where the parasites grow and divide. However, macrophages are also the main effector population involved in parasite clearance. Parasite elimination by macrophages requires the priming and development of an effector Th1 adaptive immunity driven by specific subtypes of dendritic cells. Herein, we will provide a comprehensive outline of how myeloid cells regulate innate and adaptive immunity against Leishmania, and the mechanisms used by the parasites to promote their evasion and sabotage. Understanding the interactions between Leishmania and the host myeloid cells may lead to the development of new therapeutic approaches and improved vaccination to leishmaniases, an important worldwide health problem in which current therapeutic or preventive approaches are limited.

PPARgamma in immunity and inflammation: cell types and diseases.

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Széles, Lajos; Töröcsik, Dániel; Nagy, László

2007-08-01

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

Non-classical mechanisms of transcriptional regulation by the vitamin D receptor: insights into calcium homeostasis, immune system regulation and cancer chemoprevention.

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Dimitrov, Vassil; Salehi-Tabar, Reyhaneh; An, Beum-Soo; White, John H

2014-10-01

Hormonal 1,25-dihydroxyvitamin D [1,25(OH)2D] signals through the nuclear vitamin D receptor (VDR), a ligand-regulated transcription factor. Gene expression profiling studies have revealed that 1,25(OH)2D signaling through the VDR can lead to activation or repression of target gene transcription in roughly equal proportions. Classically, transcriptional regulation by the VDR, similar to other nuclear receptors, has been characterized by its capacity to recognize high affinity cognate vitamin D response elements (VDREs), located in the regulatory regions of target genes. Several biochemical studies revealed that the VDRE-bound receptor recruits a series of coregulatory proteins, leading to transactivation of adjacent target genes. However, genome-wide and other analyses of VDR binding have revealed that a subset of VDR binding sites does not contain VDREs, and that VDREs are not associated with transcriptionally repressed VDR target genes. Work over the last ∼20 years and in particular recent findings have revealed a diverse array of mechanisms by which VDR can form complexes with several other classes of transcriptional activators, leading to repression of gene transcription. Moreover, these efforts have led to several insights into the molecular basis for the physiological regulation of calcium homeostasis, immune system function and cancer chemoprevention by 1,25(OH)2D/VDR signaling. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. Copyright © 2013 Elsevier Ltd. All rights reserved.

NEW ASPECTS OF ANTI-INFECTION IMMUNITY

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E. P. Kisseleva

2011-01-01

Full Text Available Abstract. Four types of adaptive immune response which are regulated by different T-cell populations, namely Th1, Th2, Th17 and T regs have been described. At the first time classification is based on the difference in transcription factors but not due to diversity of cytokines produced. Each population of T-lymphocytes possesses a set of unique transcription factors and directions of cell signaling. Each type of immune responses plays a key role in the protection against certain types of pathogens. The Th1-response is important against intracellular bacteria and fungi, the Th17 — against extracellular, the Th2 — against yeasts and protozoa. T-regulatory cells control all types of immune responses. Diversity of immune response mechanisms occurs due to involvement of different effector cells. The Th1-type of response is connected with macrophage activation, Th2-cells cooperate with B-lymphocytes as well as attract eosinophils and mast cells. Th17 lymphocytes stimulate neutrophils and epithelial cells. T-cell differentiation is directed by the cytokines produced by innate immune cells. Phagocytes recognize molecular patterns at the surface of pathogens via pattern-recognition receptors (PRR, become activated and synthesize cytokines. Pathogen plays important role in this process while instructing dendritic cells. Pathogen dials a special code from a number of phagocyte surface receptors, which is named as «combinatory» recognition. Phagocytes possess several different types of activation and synthesize different cytokines that direct T-lymphocytes to a certain type of differentiation.

Antitumor Immunity Is Controlled by Tetraspanin Proteins

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Fleur Schaper

2018-05-01

Full Text Available Antitumor immunity is shaped by the different types of immune cells that are present in the tumor microenvironment (TME. In particular, environmental signals (for instance, soluble factors or cell–cell contact transmitted through the plasma membrane determine whether immune cells are activated or inhibited. Tetraspanin proteins are emerging as central building blocks of the plasma membrane by their capacity to cluster immune receptors, enzymes, and signaling molecules into the tetraspanin web. Whereas some tetraspanins (CD81, CD151, CD9 are widely and broadly expressed, others (CD53, CD37, Tssc6 have an expression pattern restricted to hematopoietic cells. Studies using genetic mouse models have identified important immunological functions of these tetraspanins on different leukocyte subsets, and as such, may be involved in the immune response against tumors. While multiple studies have been performed with regards to deciphering the function of tetraspanins on cancer cells, the effect of tetraspanins on immune cells in the antitumor response remains understudied. In this review, we will focus on tetraspanins expressed by immune cells and discuss their potential role in antitumor immunity. New insights in tetraspanin function in the TME and possible prognostic and therapeutic roles of tetraspanins will be discussed.

Phylogeny, longevity and evolution of adaptive immunity

Czech Academy of Sciences Publication Activity Database

Vinkler, Michal; Albrecht, Tomáš

2011-01-01

Roč. 60, č. 3 (2011), s. 277-282 ISSN 0139-7893 R&D Projects: GA ČR GA206/08/0640; GA ČR GA206/08/1281; GA ČR GAP505/10/1871 Institutional research plan: CEZ:AV0Z60930519 Keywords : acquired immunity * evolutionary immunology * immunological priming * innate immunity * invertebrates Subject RIV: EG - Zoology Impact factor: 0.554, year: 2011

The ontogeny of the porcine immune system

Czech Academy of Sciences Publication Activity Database

Šinkora, Marek; Butler, J. E.

2009-01-01

Roč. 33, č. 3 (2009), s. 273-283 ISSN 0145-305X R&D Projects: GA ČR GA524/07/0087; GA ČR GA523/07/0088 Institutional research plan: CEZ:AV0Z50200510 Keywords : ontogeny of the porcine immune system * swine adaptive immunity * development of alpha beta and gamma delta T cells Subject RIV: EC - Immunology Impact factor: 3.290, year: 2009

Assessment of Child Immunization Coverage and Associated Factors with Full Vaccination among Children Aged 12–23 Months at Mizan Aman Town, Bench Maji Zone, Southwest Ethiopia

Science.gov (United States)

Geremew, Mesfin; Birhanu, Frehiwot

2017-01-01

Immunization remains one of the most important and cost-effective public health interventions to reduce child mortality and morbidity. Globally, it is estimated to avert between 2 and 3 million deaths each year. In Ethiopia, immunization coverage rates stagnated and remained very low for many years. Thus, this study was aimed to assess child immunization coverage and factors associated with full vaccination among children aged 12–23 months in Mizan Aman town. The study design was community-based cross-sectional survey. Data was collected by using pretested structured questionnaire. A total of 322 mothers/caretakers were interviewed. Based on vaccination card and mothers/caretakers' recall, 295 (91.6%) of the children took at least a single dose of vaccine. From total children, 27 (8.4%) were not immunized at all, 159 (49.4%) were partially immunized, and 136 (42.2%) were fully immunized. Mothers/caretakers educational level, fathers' educational level, place of delivery, maternal health care utilization, and mothers/caretakers knowledge about vaccine and vaccine-preventable disease showed significant association with full child immunization. The finding from this study revealed that child immunization coverage in the studied area was low. Thus the town health office and concerned stakeholders need to work more to improve performance of the expanded program on immunization in this area. PMID:29434643

Postnatal Innate Immune Development: From Birth to Adulthood

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Anastasia Georgountzou

2017-08-01

Full Text Available It is well established that adaptive immune responses are deficient in early life, contributing to increased mortality and morbidity. The developmental trajectories of different components of innate immunity are only recently being explored. Individual molecules, cells, or pathways of innate recognition and signaling, within different compartments/anatomical sites, demonstrate variable maturation patterns. Despite some discrepancies among published data, valuable information is emerging, showing that the developmental pattern of cytokine responses during early life is age and toll-like receptor specific, and may be modified by genetic and environmental factors. Interestingly, specific environmental exposures have been linked both to innate function modifications and the occurrence of chronic inflammatory disorders, such as respiratory allergies. As these conditions are on the rise, our knowledge on innate immune development and its modulating factors needs to be expanded. Improved understanding of the sequence of events associated with disease onset and persistence will lead toward meaningful interventions. This review describes the state-of-the-art on normal postnatal innate immune ontogeny and highlights research areas that are currently explored or should be further addressed.

Factors associated with the effect of open splenectomy for immune thrombocytopenic purpura.

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Li, Ying; Zhang, Dawei; Hua, Fanli; Gao, Song; Wu, Yangjiong; Xu, Jianmin

2017-01-01

To assess the effect and complications of open splenectomy (OS) for immune thrombocytopenic purpura (ITP) and determine preoperative factors associated with surgical effect. This was a retrospective analysis of ITP patients who failed medical therapy and were treated with OS between 1997 and 2014 at the Jinshan Hospital, China. Follow-up was 60 months. Surgical effect was determined from platelet counts and bleeding episodes. Complications were assessed including bleeding episodes. Preoperative factors were identified by logistic regression analysis. Fifty-six patients (48.2 ± 16.2 yr old; 39 females) were included. Disease course was 31.2 ± 48.2 months; 91.1% patients had preoperative platelet count effect at 1 wk, 1 month, 1 yr, and 5 yrs was in 91.1%, 92.9%, 91.1%, and 89.3% patients, respectively. Pneumonia or lower extremity thrombosis occurred in 7.1% patients. Postoperative mild, moderate, and severe bleeding occurred in 33.9%, 50.0%, and 16.1% patients, respectively. No patients required blood transfusion. Mortality was zero. Larger spleen size associated with surgical effect at 1 wk, 1 month, and 1 yr, and lower preoperative minimum platelet count associated with effect at 5 yrs (P effective treatment with less complications for the management of ITP. Lower preoperative minimum platelet count associated with successful OS at 5 yrs. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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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. © 2016 The Authors. International Journal of Experimental Pathology © 2016

Regulation of non-classical immune parameters in immune thrombocytopenic purpura mice by a spleen-invigorating, qi-replenishing and blood-containing formula

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Tiantian Li

2015-04-01

Conclusions: The SQBF had a similar effect to prednisone with regards to enhancing peripheral blood platelet counts in ITP mice. Furthermore, it decreased β-EP levels and increased VIP and SIgA, and protected the thymus. This shows that, on base of the brain-gut axis functions, some non-classical immune vascular active factors or neurotransmitters are also involved in immune responses, and also have relationship with the onset of ITP and bleeding and/or hemostasis. It needs further study to determine whether a change in these active factors is related to immediate hemostasis.

Effects of engineered nanoparticles on the innate immune system.

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Liu, Yuanchang; Hardie, Joseph; Zhang, Xianzhi; Rotello, Vincent M

2017-12-01

Engineered nanoparticles (NPs) have broad applications in industry and nanomedicine. When NPs enter the body, interactions with the immune system are unavoidable. The innate immune system, a non-specific first line of defense against potential threats to the host, immediately interacts with introduced NPs and generates complicated immune responses. Depending on their physicochemical properties, NPs can interact with cells and proteins to stimulate or suppress the innate immune response, and similarly activate or avoid the complement system. NPs size, shape, hydrophobicity and surface modification are the main factors that influence the interactions between NPs and the innate immune system. In this review, we will focus on recent reports about the relationship between the physicochemical properties of NPs and their innate immune response, and their applications in immunotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Autopolyreactivity Confers a Holistic Role in the Immune System.

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Avrameas, S

2016-04-01

In this review, we summarize and discuss some key findings from the study of naturally occurring autoantibodies. The B-cell compartment of the immune system appears to recognize almost all endogenous and environmental antigens. This ability is accomplished principally through autopolyreactive humoral and cellular immune receptors. This extended autopolyreactivity (1) along immunoglobulin gene recombination contributes to the immune system's ability to recognize a very large number of self and non-self constituents; and (2) generates a vast immune network that creates communication channels between the organism's interior and exterior. Thus, the immune system continuously evolves depending on the internal and external stimuli it encounters. Furthermore, this far-reaching network's existence implies activities resembling those of classical biological factors or activities that modulate the function of other classical biological factors. A few such antibodies have already been found. Another important concept is that natural autoantibodies are highly dependent on the presence or absence of commensal microbes in the organism. These results are in line with past and recent findings showing the fundamental influence of the microbiota on proper immune system development, and necessitate the existence of a host-microbe homeostasis. This homeostasis requires that the participating humoral and cellular receptors are able to recognize self-antigens and commensal microbes without damaging them. Autopolyreactive immune receptors expressing low affinity for both types of antigens fulfil this role. The immune system appears to play a holistic role similar to that of the nervous system. © 2016 The Foundation for the Scandinavian Journal of Immunology.

Global Immunizations: Health Promotion and Disease Prevention Worldwide.

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

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

Ebola and Immune System

OpenAIRE

KOMENAN, Alexis

2016-01-01

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

Immunization delivery in British Columbia

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Omura, John; Buxton, Jane; Kaczorowski, Janusz; Catterson, Jason; Li, Jane; Derban, Andrea; Hasselback, Paul; Machin, Shelagh; Linekin, Michelle; Morgana, Tamsin; O’Briain, Barra; Scheifele, David; Dawar, Meena

2014-01-01

Abstract Objective To explore the experiences of family physicians and pediatricians delivering immunizations, including perceived barriers and supports. Design Qualitative study using focus groups. Setting Ten cities throughout British Columbia. Participants A total of 46 family physicians or general practitioners, 10 pediatricians, and 2 residents. Methods A semistructured dialogue guide was used by a trained facilitator to explore participants’ experiences and views related to immunization delivery in British Columbia. Verbatim transcriptions were independently coded by 2 researchers. Key themes were analyzed and identified in an iterative manner using interpretive description. Main findings Physicians highly valued vaccine delivery. Factors facilitating physician-delivered immunizations included strong beliefs in the value of vaccines and having adequate information. Identified barriers included the large time commitment and insufficient communication about program changes, new vaccines, and the adult immunization program in general. Some physicians reported good relationships with local public health, while others reported the opposite experience, and this varied by geographic location. Conclusion These findings suggest that physicians are supportive of delivering vaccines. However, there are opportunities to improve the sustainability of physician-delivered immunizations. While compensation schemes remain under the purview of the provincial governments, local public health authorities can address the information needs of physicians. PMID:24627403

Osteoimmunology: Influence of the Immune System on Bone Regeneration and Consumption.

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Limmer, Andreas; Wirtz, Dieter C

2017-06-01

Background Stimulating bone regeneration is a central aim in orthopaedic and trauma surgery. Although the replacement of bone with artificial materials like cement or apatite helps to keep up bone stability, new bone often cannot be regenerated. Increasing research efforts have led to the clinical application of growth factors stimulating bone growth (e.g. bone morphogenic protein, BMP) and inhibitors preventing bone consumption (e.g. RANKL blocking antibodies). These factors mostly concentrate on stimulating osteoblast or preventing osteoclast activity. Current Situation It is widely accepted that osteoblasts and osteoclasts are central players in bone regeneration. This concept assumes that osteoblasts are responsible for bone growth while osteoclasts cause bone consumption by secreting matrix-degrading enzymes such as cathepsin K and matrix metalloproteinases (MMP). However, according to new research results, bone growth or consumption are not regulated by single cell types. It is rather the interaction of various cell types that regulates bone metabolism. While factors secreted by osteoblasts are essential for osteoclast differentiation and activation, factors secreted by activated osteoclasts are essential for osteoblast activity. In addition, recent research results imply that the influence of the immune system on bone metabolism has long been neglected. Factors secreted by macrophages or T cells strongly influence bone growth or degradation, depending on the bone microenvironment. Infections, sterile inflammation or tumour metastases not only affect bone cells directly, but also influence immune cells such as T cells indirectly. Furthermore, immune cells and bone are mechanistically regulated by similar factors such as cytokines, chemokines and transcription factors, suggesting that the definition of bone and immune cells has to be thought over. Outlook Bone and the immune system are regulated by similar mechanisms. These newly identified similarities

An immune origin of type 2 diabetes?

DEFF Research Database (Denmark)

Kolb, H; Mandrup-Poulsen, Thomas

2005-01-01

Subclinical, low-grade systemic inflammation has been observed in patients with type 2 diabetes and in those at increased risk of the disease. This may be more than an epiphenomenon. Alleles of genes encoding immune/inflammatory mediators are associated with the disease, and the two major...... environmental factors the contribute to the risk of type 2 diabetes-diet and physical activity-have a direct impact on levels of systemic immune mediators. In animal models, targeting of immune genes enhanced or suppressed the development of obesity or diabetes. Obesity is associated with the infiltration...... and proinflammatory activity of macrophages in adipose tissue, and immune mediators may be important regulators of insulin resistance, mitochondrial function, ectopic lipid storage and beta cell dysfunction or death. Intervention studies targeting these pathways would help to determine the contribution...

Skin Immunization Obviates Alcohol-Related Immune Dysfunction

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Rhonda M. Brand

2015-11-01

Full Text Available Alcoholics suffer from immune dysfunction that can impede vaccine efficacy. If ethanol (EtOH-induced immune impairment is in part a result of direct exposure of immune cells to EtOH, then reduced levels of exposure could result in less immune dysfunction. As alcohol ingestion results in lower alcohol levels in skin than blood, we hypothesized that the skin immune network may be relatively preserved, enabling skin-targeted immunizations to obviate the immune inhibitory effects of alcohol consumption on conventional vaccines. We employed the two most common chronic EtOH mouse feeding models, the liver-damaging Lieber-DeCarli (LD and liver-sparing Meadows-Cook (MC diets, to examine the roles of EtOH and/or EtOH-induced liver dysfunction on alcohol related immunosuppression. Pair-fed mice were immunized against the model antigen ovalbumin (OVA by DNA immunization or against flu by administering the protein-based influenza vaccine either systemically (IV, IM, directly to liver (hydrodynamic, or cutaneously (biolistic, ID. We measured resulting tissue EtOH levels, liver stress, regulatory T cell (Treg, and myeloid-derived suppressor cell (MDSC populations. We compared immune responsiveness by measuring delayed-type hypersensitivity (DTH, antigen-specific cytotoxic T lymphocyte (CTL, and antibody induction as a function of delivery route and feeding model. We found that, as expected, and independent of the feeding model, EtOH ingestion inhibits DTH, CTL lysis, and antigen-specific total IgG induced by traditional systemic vaccines. On the other hand, skin-targeted vaccines were equally immunogenic in alcohol-exposed and non-exposed subjects, suggesting that cutaneous immunization may result in more efficacious vaccination in alcohol-ingesting subjects.

Comparative study of lymphocytes from individuals that were vaccinated and unvaccinated against the pandemic 2009-2011 H1N1 influenza virus in Southern Brazil

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Deise Nascimento de Freitas

2015-10-01

Full Text Available ABSTRACTINTRODUCTION:While no single factor is sufficient to guarantee the success of influenza vaccine programs, knowledge of the levels of immunity in local populations is critical. Here, we analyzed influenza immunity in a population from Southern Brazil, a region with weather conditions that are distinct from those in the rest of country, where influenza infections are endemic, and where greater than 50% of the population is vaccinated annually.METHODS:Peripheral blood mononuclear cells were isolated from 40 individuals. Of these, 20 had received the H1N1 vaccine, while the remaining 20 were unvaccinated against the disease. Cells were stimulated in vitro with the trivalent post-pandemic influenza vaccine or with conserved major histocompatibility complex I (MHC I peptides derived from hemagglutinin and neuraminidase. Cell viability was then analyzed by [3-(4,5-dimethylthiazol-2-yl-2,5- diphenyltetrazolium bromide]-based colorimetric assay (MTT, and culture supernatants were assayed for helper T type 1 (Th1 and Th2-specific cytokine levels.RESULTS:Peripheral blood lymphocytes from vaccinated, but not unvaccinated, individuals exhibited significant proliferation in vitro in the presence of a cognate influenza antigen. After culturing with vaccine antigens, cells from vaccinated individuals produced similar levels of interleukin (IL-10 and interferon (IFN-γ, while those from unvaccinated individuals produced higher levels of IFN-γ than of IL-10.CONCLUSIONS:Our data indicate that peripheral blood lymphocytes from vaccinated individuals are stimulated upon encountering a cognate antigen, but did not support the hypothesis that cross-reactive responses related to previous infections can ameliorate the immune response. Moreover, monitoring IL-10 production in vaccinated individuals could comprise a valuable tool for predicting disease evolution.

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

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

2015-06-23

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

The role of the immune system in neurodegenerative disorders: Adaptive or maladaptive?

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Doty, Kevin R; Guillot-Sestier, Marie-Victoire; Town, Terrence

2015-08-18

Neurodegenerative diseases share common features, including catastrophic neuronal loss that leads to cognitive or motor dysfunction. Neuronal injury occurs in an inflammatory milieu that is populated by resident and sometimes, infiltrating, immune cells - all of which participate in a complex interplay between secreted inflammatory modulators and activated immune cell surface receptors. The importance of these immunomodulators is highlighted by the number of immune factors that have been associated with increased risk of neurodegeneration in recent genome-wide association studies. One of the more difficult tasks for designing therapeutic strategies for immune modulation against neurodegenerative diseases is teasing apart beneficial from harmful signals. In this regard, learning more about the immune components of these diseases has yielded common themes. These unifying concepts should eventually enable immune-based therapeutics for treatment of Alzheimer׳s and Parkinson׳s diseases and amyotrophic lateral sclerosis. Targeted immune modulation should be possible to temper maladaptive factors, enabling beneficial immune responses in the context of neurodegenerative diseases. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. Copyright © 2014 Elsevier B.V. All rights reserved.

U.S. Immunization program adult immunization activities and resources

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

2016-01-01

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

The Immune System in Obesity: Developing Paradigms Amidst Inconvenient Truths.

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Agrawal, Madhur; Kern, Philip A; Nikolajczyk, Barbara S

2017-08-15

Adipose tissue (AT) houses both innate and adaptive immune systems that are crucial for preserving AT function and metabolic homeostasis. In this review, we summarize recent information regarding progression of obesity-associated AT inflammation and insulin resistance. We additionally consider alterations in AT distribution and the immune system in males vs. females and among different racial populations. Innate and adaptive immune cell-derived inflammation drives insulin resistance both locally and systemically. However, new evidence also suggests that the immune system is equally vital for adipocyte differentiation and protection from ectopic lipid deposition. Furthermore, roles of anti-inflammatory immune cells such as regulatory T cells, "M2-like" macrophages, eosinophils, and mast cells are being explored, primarily due to promise of immunotherapeutic applications. Both immune responses and AT distribution are strongly influenced by factors like sex and race, which have been largely underappreciated in the field of metabolically-associated inflammation, or meta-flammation. More studies are required to recognize factors that switch inflammation from controlled to uncontrolled in obesity-associated pathogenesis and to integrate the combined effects of meta-flammation and immunometabolism. It is critical to recognize that the AT-associated immune system can be alternately beneficial and destructive; therefore, simply blocking immune responses early in obesity may not be the best clinical approach. The dearth of information on gender and race-associated disparities in metabolism, AT distribution, and the immune system suggest that a greater understanding of such differences will be critical to develop personalized treatments for obesity and the associated metabolic dysfunction.

Effector Regulatory T Cell Differentiation and Immune Homeostasis Depend on the Transcription Factor Myb.

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Dias, Sheila; D'Amico, Angela; Cretney, Erika; Liao, Yang; Tellier, Julie; Bruggeman, Christine; Almeida, Francisca F; Leahy, Jamie; Belz, Gabrielle T; Smyth, Gordon K; Shi, Wei; Nutt, Stephen L

2017-01-17

FoxP3-expressing regulatory T (Treg) cells are essential for maintaining immune homeostasis. Activated Treg cells undergo further differentiation into an effector state that highly expresses genes critical for Treg cell function, although how this process is coordinated on a transcriptional level is poorly understood. Here, we demonstrate that mice lacking the transcription factor Myb in Treg cells succumbed to a multi-organ inflammatory disease. Myb was specifically expressed in, and required for the differentiation of, thymus-derived effector Treg cells. The combination of transcriptome and genomic footprint analyses revealed that Myb directly regulated a large proportion of the gene expression specific to effector Treg cells, identifying Myb as a critical component of the gene regulatory network controlling effector Treg cell differentiation and function. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanism of immune evasion in breast cancer

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Wang, Mozhi; Zhang, Changwang; Song, Yongxi; Wang, Zhenning; Wang, Yaojia; Luo, Fang; Xu, Yujie; Zhao, Yi; Wu, Zhonghua; Xu, Yingying

2017-01-01

Breast cancer (BC) is the most common malignant tumor among women, with high morbidity and mortality. Its onset, development, metastasis, and prognosis vary among individuals due to the interactions between tumors and host immunity. Many diverse mechanisms have been associated with BC, with immune evasion being the most widely studied to date. Tumor cells can escape from the body’s immune response, which targets abnormal components and foreign bodies, using different approaches including modification of surface antigens and modulation of the surrounding environment. In this review, we summarize the mechanisms and factors that impact the immunoediting process and analyze their functions in detail. PMID:28352189

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.

The fungal quorum-sensing molecule farnesol activates innate immune cells but suppresses cellular adaptive immunity.

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Leonhardt, Ines; Spielberg, Steffi; Weber, Michael; Albrecht-Eckardt, Daniela; Bläss, Markus; Claus, Ralf; Barz, Dagmar; Scherlach, Kirstin; Hertweck, Christian; Löffler, Jürgen; Hünniger, Kerstin; Kurzai, Oliver

2015-03-17

Farnesol, produced by the polymorphic fungus Candida albicans, is the first quorum-sensing molecule discovered in eukaryotes. Its main function is control of C. albicans filamentation, a process closely linked to pathogenesis. In this study, we analyzed the effects of farnesol on innate immune cells known to be important for fungal clearance and protective immunity. Farnesol enhanced the expression of activation markers on monocytes (CD86 and HLA-DR) and neutrophils (CD66b and CD11b) and promoted oxidative burst and the release of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α] and macrophage inflammatory protein 1 alpha [MIP-1α]). However, this activation did not result in enhanced fungal uptake or killing. Furthermore, the differentiation of monocytes to immature dendritic cells (iDC) was significantly affected by farnesol. Several markers important for maturation and antigen presentation like CD1a, CD83, CD86, and CD80 were significantly reduced in the presence of farnesol. Furthermore, farnesol modulated migrational behavior and cytokine release and impaired the ability of DC to induce T cell proliferation. Of major importance was the absence of interleukin 12 (IL-12) induction in iDC generated in the presence of farnesol. Transcriptome analyses revealed a farnesol-induced shift in effector molecule expression and a down-regulation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor during monocytes to iDC differentiation. Taken together, our data unveil the ability of farnesol to act as a virulence factor of C. albicans by influencing innate immune cells to promote inflammation and mitigating the Th1 response, which is essential for fungal clearance. Farnesol is a quorum-sensing molecule which controls morphological plasticity of the pathogenic yeast Candida albicans. As such, it is a major mediator of intraspecies communication. Here, we investigated the impact of farnesol on human innate immune cells known to be

Immunization Information System and Informatics to Promote Immunizations: Perspective From Minnesota Immunization Information Connection.

Science.gov (United States)

Muscoplat, Miriam Halstead; Rajamani, Sripriya

2017-01-01

The vision for management of immunization information is availability of real-time consolidated data and services for all ages, to clinical, public health, and other stakeholders. This is being executed through Immunization Information Systems (IISs), which are population-based and confidential computerized systems present in most US states and territories. Immunization Information Systems offer many functionalities, such as immunization assessment reports, client follow-up, reminder/recall feature, vaccine management tools, state-supplied vaccine ordering, comprehensive immunization history, clinical decision support/vaccine forecasting and recommendations, data processing, and data exchange. This perspective article will present various informatics tools in an IIS, in the context of the Minnesota Immunization Information Connection.

Can investments in health systems strategies lead to changes in immunization coverage?

Science.gov (United States)

Brenzel, Logan

2014-04-01

National immunization programs in developing countries have made major strides to immunize the world's children, increasing full coverage to 83% of children. However, the World Health Organization estimates that 22 million children less than five years of age are left unvaccinated, and coverage levels have been plateauing for nearly a decade. This paper describes the evidence on factors contributing to low vaccination uptake, and describes the connection between these factors and the documented strategies and interventions that can lead to changes in immunization outcomes. The author suggests that investments in these areas may contribute more effectively to immunization coverage and also have positive spill-over benefits for health systems. The paper concludes that while some good quality evidence exists of what works and may contribute to immunization outcomes, the quality of evidence needs to improve and major gaps need to be addressed.

Alternative theories: Pregnancy and immune tolerance.

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Bonney, Elizabeth A

2017-09-01

For some time, reproductive immunologists have worked to understand the balance between maternal tolerance of the fetus, maternal health, and fetal protection which leads to successful pregnancy in mammalian species. We have always understood the potential importance of multiple factors, including nutrition, genetics, anatomy, hormonal regulation, environmental insult and many others. Yet, we still struggle to combine our knowledge of these factors and immunology to finally understand complex diseases of pregnancy, such as preeclampsia. Data, and potentially other factors (e.g. politics, economics), support the work to fit pregnancy into classical immune theory driven by the concept of self-non-self-discrimination. However, based on data, many classical theorists call pregnancy "a special case." This review is a first-pass suggestion to attempt to view three models of immune system activation and tolerance as potential alternatives to classical self-non-self-discrimination and to propose a theoretical framework to view them in the context of pregnancy. Copyright © 2017 Elsevier B.V. All rights reserved.

Super-enhancers: Asset management in immune cell genomes.

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Witte, Steven; O'Shea, John J; Vahedi, Golnaz

2015-09-01

Super-enhancers (SEs) are regions of the genome consisting of clusters of regulatory elements bound with very high amounts of transcription factors, and this architecture appears to be the hallmark of genes and noncoding RNAs linked with cell identity. Recent studies have identified SEs in CD4(+) T cells and have further linked these regions to single nucleotide polymorphisms (SNPs) associated with immune-mediated disorders, pointing to an important role for these structures in the T cell differentiation and function. Here we review the features that define SEs, and discuss their function within the broader understanding of the mechanisms that define immune cell identity and function. We propose that SEs present crucial regulatory hubs, coordinating intrinsic and extrinsic differentiation signals, and argue that delineating these regions will provide important insight into the factors and mechanisms that define immune cell identity. Copyright © 2015 Elsevier Ltd. All rights reserved.

The role of retinoic acid in tolerance and immunity.

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Hall, Jason A; Grainger, John R; Spencer, Sean P; Belkaid, Yasmine

2011-07-22

Vitamin A elicits a broad array of immune responses through its metabolite, retinoic acid (RA). Recent evidence indicates that loss of RA leads to impaired immunity, whereas excess RA can potentially promote inflammatory disorders. In this review, we discuss recent advances showcasing the crucial contributions of RA to both immunological tolerance and the elicitation of adaptive immune responses. Further, we provide a comprehensive overview of the cell types and factors that control the production of RA and discuss how host perturbations may affect the ability of this metabolite to control tolerance and immunity or to instigate pathology. Copyright © 2011 Elsevier Inc. All rights reserved.

[Evasion of anti-infectious immunity by Brucella - A review].

Science.gov (United States)

Quan, Wurong; Yang, Yongjie

2016-05-04

Brucellosis, caused by Brucella species, is a worldwide zoonosis. As facultative intracellular pathogens, Brucella possess non-classical virulence factor, but its virulence is very powerful and can elicit chronic infections of both animals and humans. Evasion of host anti-infectious immunity is a prerequisite for chronic infections, this ability appears increasingly crucial for Brucella virulence. As successful pathogens, Brucella can escape or suppress innate immunity and modulate adaptive immunity to establish long lasting infections in host cells. In this review, we address the molecular mechanisms of Brucella to evade anti-infectious immunity. This will shed new insights on Brucella virulence and will, potentially, open new prophylactic avenues.

Allelic barley MLA immune receptors recognize sequence-unrelated avirulence effectors of the powdery mildew pathogen.

Science.gov (United States)

Lu, Xunli; Kracher, Barbara; Saur, Isabel M L; Bauer, Saskia; Ellwood, Simon R; Wise, Roger; Yaeno, Takashi; Maekawa, Takaki; Schulze-Lefert, Paul

2016-10-18

Disease-resistance genes encoding intracellular nucleotide-binding domain and leucine-rich repeat proteins (NLRs) are key components of the plant innate immune system and typically detect the presence of isolate-specific avirulence (AVR) effectors from pathogens. NLR genes define the fastest-evolving gene family of flowering plants and are often arranged in gene clusters containing multiple paralogs, contributing to copy number and allele-specific NLR variation within a host species. Barley mildew resistance locus a (Mla) has been subject to extensive functional diversification, resulting in allelic resistance specificities each recognizing a cognate, but largely unidentified, AVR a gene of the powdery mildew fungus, Blumeria graminis f. sp. hordei (Bgh). We applied a transcriptome-wide association study among 17 Bgh isolates containing different AVR a genes and identified AVR a1 and AVR a13 , encoding candidate-secreted effectors recognized by Mla1 and Mla13 alleles, respectively. Transient expression of the effector genes in barley leaves or protoplasts was sufficient to trigger Mla1 or Mla13 allele-specific cell death, a hallmark of NLR receptor-mediated immunity. AVR a1 and AVR a13 are phylogenetically unrelated, demonstrating that certain allelic MLA receptors evolved to recognize sequence-unrelated effectors. They are ancient effectors because corresponding loci are present in wheat powdery mildew. AVR A1 recognition by barley MLA1 is retained in transgenic Arabidopsis, indicating that AVR A1 directly binds MLA1 or that its recognition involves an evolutionarily conserved host target of AVR A1 Furthermore, analysis of transcriptome-wide sequence variation among the Bgh isolates provides evidence for Bgh population structure that is partially linked to geographic isolation.

Arthropod Innate Immune Systems and Vector-Borne Diseases.

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

2017-02-21

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

Schizophrenia and the immune system: pathophysiology, prevention, and treatment.

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Richard, Michelle D; Brahm, Nancy C

2012-05-01

Published evidence on established and theoretical connections between immune system dysfunction and schizophrenia is reviewed, with a discussion of developments in the search for immunologically-targeted treatments. A growing body of evidence indicates that immunologic influences may play an important role in the etiology and course of schizophrenia. A literature search identified more than 100 articles pertaining to suspected immunologic influences on schizophrenia published over the past 15 years. Schizophrenia researchers have explored a wide range of potential immune system-related causal or contributory factors, including neurobiological and neuroanatomical disorders, genetic abnormalities, and environmental influences such as maternal perinatal infection. Efforts to establish an immunologic basis for schizophrenia and identify reliable immune markers continue to be hindered by sampling challenges and methodological problems. In aggregate, the available evidence indicates that at least some cases of schizophrenia have an immunologic component, suggesting that immune-focused prevention strategies (e.g., counseling of pregnant women to avoid immune stressors) and close monitoring of at-risk children are appropriate. While antipsychotics remain the standard treatments for schizophrenia, a variety of drugs with immunologic effects have been investigated as adjunctive therapies, with variable and sometimes conflicting results; these include the cyclooxygenase-2 inhibitor celecoxib, immune-modulating agents (e.g., azathioprine and various anticytokine agents such as atlizumab, anakinra, and tumor necrosis factor-α blockers), and an investigational anti-interferon-γ agent. The published evidence indicates that immune system dysfunction related to genetic, environmental, and neurobiological influences may play a role in the etiology of schizophrenia in a subset of patients.

The Progress of T Cell Immunity Related to Prognosis in Gastric Cancer

OpenAIRE

Ming Wei; Duo Shen; Sachin Mulmi Shrestha; Juan Liu; Junyi Zhang; Ying Yin

2018-01-01

Gastric cancer is the fifth most common malignancy all over the world, and the factors that can affect progress and prognosis of the gastric cancer patients are various, such as TNM stages, invasive depth, and lymph node metastasis ratio. T cell immunity is important component of human immunity system and immunity responding to tumor and dysfunction or imbalance of T cell immunity will lead to serious outcomes for body. T cell immunity includes many different types of cells, CD4+ T cell, CD8+...

Perinatal Environmental Effects on the Neonatal Immune System

DEFF Research Database (Denmark)

Thysen, Anna Hammerich

2014-01-01

are thought to be programmed in utero supporting a role of the early environment. The aim of the present PhD thesis was to study if known risk factors are imprinted in the immune system of newborns. The hypotheses were that cesarean section and season of birth would influence the immune signature in early...... life. Both are known to be associated with disease. We analyzed the distribution of circulating immune cells from cord blood in the children part of the ongoing unselected COPSAC2010 birth cohort by multi-color flow cytometry. Moreover, airway mucosal cytokines and chemokines of 1-month-old children...

Aedes aegypti Molecular Responses to Zika Virus: Modulation of Infection by the Toll and Jak/Stat Immune Pathways and Virus Host Factors

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Yesseinia I. Angleró-Rodríguez

2017-10-01

Full Text Available Zika (ZIKV and dengue virus (DENV are transmitted to humans by Aedes mosquitoes. However, the molecular interactions between the vector and ZIKV remain largely unexplored. In this work, we further investigated the tropism of ZIKV in two different Aedes aegypti strains and show that the virus infection kinetics, tissue migration, and susceptibility to infection differ between mosquito strains. We also compare the vector transcriptome changes upon ZIKV or DENV infection demonstrating that 40% of the mosquito’s midgut infection-responsive transcriptome is virus-specific at 7 days after virus ingestion. Regulated genes included key factors of the mosquito’s anti-viral immunity. Comparison of the ZIKV and DENV infection-responsive transcriptome data to those available for yellow fever virus and West Nile virus identified 26 genes likely to play key roles in virus infection of Aedes mosquitoes. Through reverse genetic analyses, we show that the Toll and the Jak/Stat innate immune pathways mediate increased resistance to ZIKV infection, and the conserved DENV host factors vATPase and inosine-5′-monophosphate dehydrogenase are also utilized for ZIKV infection.

Imbalanced immune homeostasis in immune thrombocytopenia.

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Yazdanbakhsh, Karina

2016-04-01

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

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

International Nuclear Information System (INIS)

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

2010-01-01

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

Immune Privilege and Eye-Derived T-Regulatory Cells

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Hiroshi Keino

2018-01-01

Full Text Available Certain cellular components of the eye, such as neural retina, are unable to regenerate and replicate after destructive inflammation. Ocular immune privilege provides the eye with immune protection against intraocular inflammation in order to minimize the risk to vision integrity. The eye and immune system use strategies to maintain the ocular immune privilege by regulating the innate and adaptive immune response, which includes immunological ignorance, peripheral tolerance to eye-derived antigens, and intraocular immunosuppressive microenvironment. In this review, we summarize current knowledge regarding the molecular mechanism responsible for the development and maintenance of ocular immune privilege via regulatory T cells (Tregs, which are generated by the anterior chamber-associated immune deviation (ACAID, and ocular resident cells including corneal endothelial (CE cells, ocular pigment epithelial (PE cells, and aqueous humor. Furthermore, we examined the therapeutic potential of Tregs generated by RPE cells that express transforming growth factor beta (TGF-β, cytotoxic T lymphocyte-associated antigen-2 alpha (CTLA-2α, and retinoic acid for autoimmune uveoretinitis and evaluated a new strategy using human RPE-induced Tregs for clinical application in inflammatory ocular disease. We believe that a better understanding of the ocular immune privilege associated with Tregs might offer a new approach with regard to therapeutic interventions for ocular autoimmunity.

Immune Privilege and Eye-Derived T-Regulatory Cells.

Science.gov (United States)

Keino, Hiroshi; Horie, Shintaro; Sugita, Sunao

2018-01-01

Certain cellular components of the eye, such as neural retina, are unable to regenerate and replicate after destructive inflammation. Ocular immune privilege provides the eye with immune protection against intraocular inflammation in order to minimize the risk to vision integrity. The eye and immune system use strategies to maintain the ocular immune privilege by regulating the innate and adaptive immune response, which includes immunological ignorance, peripheral tolerance to eye-derived antigens, and intraocular immunosuppressive microenvironment. In this review, we summarize current knowledge regarding the molecular mechanism responsible for the development and maintenance of ocular immune privilege via regulatory T cells (Tregs), which are generated by the anterior chamber-associated immune deviation (ACAID), and ocular resident cells including corneal endothelial (CE) cells, ocular pigment epithelial (PE) cells, and aqueous humor. Furthermore, we examined the therapeutic potential of Tregs generated by RPE cells that express transforming growth factor beta (TGF- β ), cytotoxic T lymphocyte-associated antigen-2 alpha (CTLA-2 α ), and retinoic acid for autoimmune uveoretinitis and evaluated a new strategy using human RPE-induced Tregs for clinical application in inflammatory ocular disease. We believe that a better understanding of the ocular immune privilege associated with Tregs might offer a new approach with regard to therapeutic interventions for ocular autoimmunity.

Immunizing Children

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Geraldine Jody Macdonald

2014-11-01

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

Immunological considerations regarding parental concerns on pediatric immunizations.

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Nicoli, Francesco; Appay, Victor

2017-05-25

Despite the fundamental role of vaccines in the decline of infant mortality, parents may decide to decline vaccination for their own children. Many factors may influence this decision, such as the belief that the infant immune system is weakened by vaccines, and concerns have been raised about the number of vaccines and the early age at which they are administered. Studies focused on the infant immune system and its reaction to immunizations, summarized in this review, show that vaccines can overcome those suboptimal features of infant immune system that render them more at risk of infections and of their severe manifestations. In addition, many vaccines have been shown to improve heterologous innate and adaptive immunity resulting in lower mortality rates for fully vaccinated children. Thus, multiple vaccinations are necessary and not dangerous, as infants can respond to several antigens as well as when responding to single stimuli. Current immunization schedules have been developed and tested to avoid vaccine interference, improve benefits and reduce side effects compared to single administrations. The infant immune system is therefore capable, early after birth, of managing several antigenic challenges and exploits them to prompt its development. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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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.

Role of Osmolytes in Regulating Immune System.

Science.gov (United States)

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

2016-01-01

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

Radiotherapy and antitumoral immunity. Fundamentals of immunooncology

International Nuclear Information System (INIS)

Klimovich, V.B.

1982-01-01

The fundamental states of immunooncology are described briefly: conception of immunologic inspection, antiblastomic immunologic factors, antigeny of tumor cells and mechanisms of slipping out of immune inspection, problastomic immunologic factors. The conclusion is made that tumor formation and extenstion go on under the action of opposite directed but not mutually exclusive factors of immunologic nature. Growth rate and regression of neoplasm are determined by balance between antiblastomic mechanism activity and activity of problastomic factors and factors of immunoresistant neoplasms

Measures of the constitutive immune system are linked to diet and roosting habits of neotropical bats.

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Karin Schneeberger

Full Text Available Ecological and social factors are central in the emergence and transmission of infectious diseases, thus bearing the potential for shaping a species' immune functions. Although previous studies demonstrated a link between social factors and the cellular immune system for captive mammals, it is yet poorly understood how ecological factors are connected with the different branches of the immune system in wild populations. Here, we tested how variation in aspects of the constitutive cellular and humoral immune system of free ranging bats is associated with two ecological factors that likely influence the putative risk of species to become infected by parasites and pathogens: diet and shelter. We found that white blood cell counts of 24 syntopic Neotropical bat species varied with the species' diet and body mass. Bats that included at least partially vertebrates in their diet exhibited the highest white blood cell counts, followed by phytophagous and insectivorous species, which is in agreement with the assumption that the immune system varies with the pathogen transmission risk of a trophic level. The soluble part of the constitutive immune response, assessed by an in vitro bacterial killing assay, decreased with increasing roost permanence. Our results suggest that the ecology is an important factor in the evolution of the immune system in bats and probably also other mammals.

Cancer exosomes and NKG2D receptor-ligand interactions: impairing NKG2D-mediated cytotoxicity and anti-tumour immune surveillance.

Science.gov (United States)

Mincheva-Nilsson, Lucia; Baranov, Vladimir

2014-10-01

Human cancers constitutively produce and release endosome-derived nanometer-sized vesicles called exosomes that carry biologically active proteins, messenger and micro RNAs and serve as vehicles of intercellular communication. The tumour exosomes are present in the blood, urine and various malignant effusions such as peritoneal and pleural fluid of cancer patients and can modulate immune cells and responses thus deranging the immune system of cancer patients and giving advantage to the cancer to establish and spread itself. Here, the role of exosomes in the NKG2D receptor-ligand system's interactions is discussed. The activating NK cell receptor NKG2D and its multiple ligands, the MHC class I-related chain (MIC) A/B and the retinoic acid transcript-1/UL-16 binding proteins (RAET1/ULBP) 1-6 comprise a powerful stress-inducible danger detector system that targets infected, inflamed and malignantly transformed cells and plays a decisive role in anti-tumour immune surveillance. Mounting evidence reveals that the MIC- and RAET1/ULBP ligand family members are enriched in the endosomal compartment of various tumour cells and expressed and released into the intercellular space and bodily fluids on exosomes thus preserving their entire molecule, three-dimensional protein structure and biologic activity. The NKG2D ligand-expressing exosomes serve as decoys with a powerful ability to down regulate the cognate receptor and impair the cytotoxic function of NK-, NKT-, gamma/delta- and cytotoxic T cells. This review summarizes recent findings concerning the role of NKG2D receptor-ligand system in cancer with emphasis on regulation of NKG2D ligand expression and the immunosuppressive role of exosomally expressed NKG2D ligands. Copyright © 2014 Elsevier Ltd. All rights reserved.

Th17 cell-mediated immune responses promote mast cell proliferation by triggering stem cell factor in keratinocytes

International Nuclear Information System (INIS)

Cho, Kyung-Ah; Park, Minhwa; Kim, Yu-Hee; Woo, So-Youn

2017-01-01

Although mast cells are traditionally thought to function as effector cells in allergic responses, they have increasingly been recognized as important regulators of various immune responses. Mast cells mature locally; thus, tissue-specific influences are important for promoting mast cell accumulation and survival in the skin and the gastrointestinal tract. In this study, we determined the effects of keratinocytes on mast cell accumulation during Th17-mediated skin inflammation. We observed increases in dermal mast cells in imiquimod-induced psoriatic dermatitis in mice accompanied by the expression of epidermal stem cell factor (SCF), a critical mast cell growth factor. Similar to mouse epidermal keratinocytes, SCF was highly expressed in the human HaCaT keratinocyte cell line following stimulation with IL−17. Further, keratinocytes promoted mast cell proliferation following stimulation with IL−17 in vitro. However, the effects of keratinocytes on mast cells were significantly diminished in the presence of anti−CD117 (stem cell factor receptor) blocking antibodies. Taken together, our results revealed that the Th17-mediated inflammatory environment promotes mast cell accumulation through keratinocyte-derived SCF. - Highlights: • Psoriasis-like skin inflammation increase dermal mast cells. • Keratinocyte produce stem cell factor in psoriasis-like skin inflammation. • Keratinocyte promote mast cell proliferation by stem cell factor dependent manner

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.

Secondary recurrent miscarriage and H-Y immunity

DEFF Research Database (Denmark)

Nielsen, Henriette Svarre

2011-01-01

BACKGROUND Approximately half recurrent miscarriage (RM) cases remain unexplained after standard investigations. Secondary RM (SRM) is, in contrast to primary RM, preceded by a birth, which increases the transfer of fetal cells into the maternal circulation. Mothers of boys are often immunized...... against male-specific minor histocompatibility (H-Y) antigens, and H-Y immunity can cause graft-versus-host disease after stem-cell transplantation. We proposed the H-Y hypothesis that aberrant H-Y immunity is a causal factor for SRM. METHODS This is a critical review of the H-Y hypothesis based on own....... Maternal carriage of HLA-class II alleles presenting H-Y antigens to immune cells is associated with a reduced live birth rate and increased risk of obstetric complications in surviving pregnancies in SRM patients with a firstborn boy. In early pregnancy, both antibodies against HLA and H-Y antigens...

Mechanisms for eco-immunity in a changing enviroment: how does the coral innate immune system contend with climate change?

Science.gov (United States)

Traylor-Knowles, N. G.

2016-02-01

Innate immunity plays a central role in maintaining homeostasis, and within the context of impending climate change scenarios, understanding how this system works is critical. However, the actual mechanisms involved in the evolution of the innate immune system are largely unknown. Cnidaria (including corals, sea anemones and jellyfish) are well suited for studying the fundamental functions of innate immunity because they share a common ancestor with bilaterians. This study will highlight the transcriptomic changes during a heat shock in the coral Acropora hyacinthus of American Samoa, examining the temporal changes, every half an hour for 5 hours. We hypothesize that genes involved in innate immunity, and extracellular matrix maintenance will be key components to the heat stress response. This presentation will highlight the novel role of the tumor necrosis factor receptor gene family as a responder to heat stress and present future directions for this developing field in coral reef research.

[The role of protein glycosylation in immune system].

Science.gov (United States)

Ząbczyńska, Marta; Pocheć, Ewa

2015-01-01

Glycosylation is one of the most frequent post-translational modifications of proteins. The majority of cell surface and secreted proteins involved in immune response is glycosylated. The structural diversity of glycans depends on monosaccharide composition, type of glycosidic linkage and branching. These structural modifications determine a great variability of glycoproteins. The oligosaccharide components of proteins are regulated mostly by expression of glycosyltransferases and glycosidases and many environmental factors. Glycosylation influences the function of all immune cells. Glycans play a crucial role in intercellular contacts and leukocytes migration. These interactions are important in activation and proliferation of leukocytes and during immune response. The key immune proteins, such as TCR, MHC, TLR and antibodies are glycosylated. Sugars on the surface of pathogens and self-surface glycoproteins are recognized by special carbohydrate binding proteins called lectins. Changes of glycan structure are common in many pathological processes occurring in immune system, therefore they are used as molecular markers of different diseases.

"The Impact of Mycobacterium tuberculosis Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" - Meeting report.

Science.gov (United States)

Boggiano, Cesar; Eichelberg, Katrin; Ramachandra, Lakshmi; Shea, Jaqueline; Ramakrishnan, Lalita; Behar, Samuel; Ernst, Joel D; Porcelli, Steven A; Maeurer, Markus; Kornfeld, Hardy

2017-06-14

Tuberculosis (TB) is the major cause of death from infectious diseases around the world, particularly in HIV infected individuals. TB vaccine design and development have been focused on improving Bacille Calmette-Guérin (BCG) and evaluating recombinant and viral vector expressed Mycobacterium tuberculosis (Mtb) proteins, for boosting BCG-primed immunity, but these approaches have not yet yielded significant improvements over the modest effects of BCG in protecting against infection or disease. On March 7-8, 2016, the National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on "The Impact of Mtb Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" with the goal of defining immune mechanisms that could be targeted through novel research approaches, to inform vaccine design and immune therapeutic interventions for prevention of TB. The workshop addressed early infection events, the impact of Mtb evolution on the development and maintenance of an adaptive immune response, and the factors that influence protection against and progression to active disease. Scientific gaps and areas of study to revitalize and accelerate TB vaccine design were discussed and prioritized. These included a comprehensive evaluation of innate and Mtb-specific adaptive immune responses in the lung at different stages of disease; determining the role of B cells and antibodies (Abs) during Mtb infection; development of better assays to measure Mtb burden following exposure, infection, during latency and after treatment, and approaches to improving current animal models to study Mtb immunogenicity, TB disease and transmission. Copyright © 2017.

Antiretroviral therapy, immune suppression and renal impairment in HIV-positive persons

DEFF Research Database (Denmark)

Nielsen, Lene Ryom; Mocroft, Amanda; Lundgren, Jens D

2014-01-01

The purpose of this article is to review recent literature on antiretroviral treatment (ART) and immune suppression as risk factors for renal impairment in HIV-positive persons, and to discuss pending research questions within this field.......The purpose of this article is to review recent literature on antiretroviral treatment (ART) and immune suppression as risk factors for renal impairment in HIV-positive persons, and to discuss pending research questions within this field....

The Skin Microbiome: Is It Affected by UV-induced Immune Suppression?

OpenAIRE

Patra, VijayKumar; Byrne, Scott N.; Wolf, Peter

2016-01-01

Human skin apart from functioning as a physical barricade to stop the entry of pathogens, also hosts innumerable commensal organisms. The skin cells and the immune system constantly interact with microbes, to maintain cutaneous homeostasis, despite the challenges offered by various environmental factors. A major environmental factor affecting the skin is ultraviolet radiation (UV-R) from sunlight. UV-R is well known to modulate the immune system, which can be both beneficial and deleterious. ...

Anterior Chamber-Associated Immune Deviation (ACAID: An Acute Response to Ocular Insult Protects from Future Immune-Mediated Damage?

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Robert E. Cone

2009-01-01

Full Text Available The “immune privilege” that inhibits immune defense mechanisms that could lead to damage to sensitive ocular tissue is based on the expression of immunosuppressive factors on ocular tissue and in ocular fluids. In addition to this environmental protection, the injection of antigen into the anterior chamber or infection in the anterior chamber induces a systemic suppression of potentially damaging cell-mediated and humoral responses to the antigen. Here we discuss evidence that suggests that Anterior Chamber-Associated Immune Deviation (ACAID a is initiated by an ocular response to moderate inflammation that leads to a systemic immunoregulatory response. Injection into the anterior chamber induces a rise in TNF-α and MCP-1 in aqueous humor and an infiltration of circulating F4/80 + monocytes that home to the iris. The induction of ACAID is dependent on this infiltration of circulating monocytes that eventually emigrate to the thymus and spleen where they induce regulatory T cells that inhibit the inductive or effector phases of a cell-mediated immune response. ACAID therefore protects the eye from the collateral damage of an immune response to infection by suppressing a future potentially damaging response to infection.

Impact of pharmacists providing immunizations on adolescent influenza immunization.

Science.gov (United States)

Robison, Steve G

2016-01-01

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

Lung Homeostasis: Influence of Age, Microbes, and the Immune System.

Science.gov (United States)

Lloyd, Clare M; Marsland, Benjamin J

2017-04-18

Pulmonary immune homeostasis is maintained by a network of tissue-resident cells that continually monitor the external environment, and in health, instruct tolerance to innocuous inhaled particles while ensuring that efficient and rapid immune responses can be mounted against invading pathogens. Here we review the multiple pathways that underlie effective lung immunity in health, and discuss how these may be affected by external environmental factors and contribute to chronic inflammation during disease. In this context, we examine the current understanding of the impact of the microbiota in immune development and function and in the setting of the threshold for immune responses that maintains the balance between tolerance and chronic inflammation in the lung. We propose that host interactions with microbes are critical for establishing the immune landscape of the lungs. Copyright © 2017 Elsevier Inc. All rights reserved.

Tumor-altered dendritic cell function: implications for anti-tumor immunity

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Kristian Michael Hargadon

2013-07-01

Full Text Available Dendritic cells are key regulators of both innate and adaptive immunity, and the array of immunoregulatory functions exhibited by these cells is dictated by their differentiation, maturation, and activation status. Although a major role for these cells in the induction of immunity to pathogens has long been appreciated, data accumulated over the last several years has demonstrated that DC are also critical regulators of anti-tumor immune responses. However, despite the potential for stimulation of robust anti-tumor immunity by DC, tumor-altered DC function has been observed in many cancer patients and tumor-bearing animals and is often associated with tumor immune escape. Such dysfunction has significant implications for both the induction of natural anti-tumor immune responses as well as the efficacy of immunotherapeutic strategies that target endogenous DC in situ or that employ exogenous DC as part of anti-cancer immunization maneuvers. In this review, the major types of tumor-altered DC function will be described, with emphasis on recent insights into the mechanistic bases for the inhibition of DC differentiation from hematopoietic precursors, the altered programming of DC precursors to differentiate into myeloid-derived suppressor cells or tumor-associated macrophages, the suppression of DC maturation and activation, and the induction of immunoregulatory DC by tumors, tumor-derived factors, and tumor-associated cells within the milieu of the tumor microenvironment. The impact of these tumor-altered cells on the quality of the overall anti-tumor immune response will also be discussed. Finally, this review will also highlight questions concerning tumor-altered DC function that remain unanswered, and it will address factors that have limited advances in the study of this phenomenon in order to focus future research efforts in the field on identifying strategies for interfering with tumor-associated DC dysfunction and improving DC-mediated anti

Factors affecting HPV vaccine acceptance in west Austria: Do we need to revise the current immunization scheme?

Science.gov (United States)

Borena, Wegene; Luckner-Hornischer, Anita; Katzgraber, Franz; Holm-von Laer, Dorothee

2016-12-01

Austria introduced a school-based gender-neutral human papillomavirus (HPV) immunization program in February 2014. In order to assure high coverage, factors influencing acceptance of the vaccine need to be identified. In this study we aim to assess parents' attitude and related socio-demographic factors in relation to the newly implemented gender-neutral, school-based HPV Immunization program. Parents of 4th grade school children in 20 randomly selected primary schools were asked to fill out questionnaires on socio-demographic factors and on the level of information and attitude towards HPV infection and HPV vaccine. A total of 439 parents with 449 vaccine eligible children participated in the study. Fifty nine percent of vaccine eligible girls and 51.8% of eligible boys received the first dose of the vaccine. Fear of side effects and child being too young for the vaccine were the most commonly cited reasons by parents electing not to let child receive the vaccine. Children who had received other school-based vaccines have more than fifteen times higher probability of receiving HPV vaccine. To have received HPV-related information from physicians positively influenced vaccine acceptance (OR (95% CI)=1.60 (1.06-2.43)). Higher paternal (fathers') educational status significantly increased the chances of a male child to be HPV vaccinated (OR (95% CI)=2.45 (1.29-4.78)). Despite the efforts to provide HPV vaccine free-of-costs and as a school-based program, the study found that a significant proportion of vaccine eligible children failed to receive the vaccine. Involvement front line physicians and men with higher educational status may be utilised by public health policy makers in the effort to increase awareness. For a better acceptability of the vaccine, there is a need to consider lifting the age of "eligibility" for the school-based vaccination program. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Structure, function and subcellular localization of the potato Resistance protein Rx1

NARCIS (Netherlands)

Slootweg, E.J.

2009-01-01

Resistance proteins are part of the plant’s immune system and mediate a defence response upon recognizing their cognate pathogens. They are thought to be present in the cell as part of a larger protein complex. The modular architecture of R proteins suggests that they form a scaffold for various

Immune cells in term and preterm labor

Science.gov (United States)

Gomez-Lopez, Nardhy; StLouis, Derek; Lehr, Marcus A; Sanchez-Rodriguez, Elly N; Arenas-Hernandez, Marcia

2014-01-01

Labor resembles an inflammatory response that includes secretion of cytokines/chemokines by resident and infiltrating immune cells into reproductive tissues and the maternal/fetal interface. Untimely activation of these inflammatory pathways leads to preterm labor, which can result in preterm birth. Preterm birth is a major determinant of neonatal mortality and morbidity; therefore, the elucidation of the process of labor at a cellular and molecular level is essential for understanding the pathophysiology of preterm labor. Here, we summarize the role of innate and adaptive immune cells in the physiological or pathological activation of labor. We review published literature regarding the role of innate and adaptive immune cells in the cervix, myometrium, fetal membranes, decidua and the fetus in late pregnancy and labor at term and preterm. Accumulating evidence suggests that innate immune cells (neutrophils, macrophages and mast cells) mediate the process of labor by releasing pro-inflammatory factors such as cytokines, chemokines and matrix metalloproteinases. Adaptive immune cells (T-cell subsets and B cells) participate in the maintenance of fetomaternal tolerance during pregnancy, and an alteration in their function or abundance may lead to labor at term or preterm. Also, immune cells that bridge the innate and adaptive immune systems (natural killer T (NKT) cells and dendritic cells (DCs)) seem to participate in the pathophysiology of preterm labor. In conclusion, a balance between innate and adaptive immune cells is required in order to sustain pregnancy; an alteration of this balance will lead to labor at term or preterm. PMID:24954221

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

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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.

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...

Regionalized Development and Maintenance of the Intestinal Adaptive Immune Landscape

DEFF Research Database (Denmark)

Agace, William Winston; McCoy, Kathy D.

2017-01-01

The intestinal immune system has the daunting task of protecting us from pathogenic insults while limiting inflammatory responses against the resident commensal microbiota and providing tolerance to food antigens. This role is particularly impressive when one considers the vast mucosal surface...... and changing landscape that the intestinal immune system must monitor. In this review, we highlight regional differences in the development and composition of the adaptive immune landscape of the intestine and the impact of local intrinsic and environmental factors that shape this process. To conclude, we...... review the evidence for a critical window of opportunity for early-life exposures that affect immune development and alter disease susceptibility later in life....

Induction of antitumor immunity through xenoplacental immunization

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Agadjanyan Michael G

2006-05-01

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

The Skin Microbiome: Is It Affected by UV-induced Immune Suppression?

Science.gov (United States)

Patra, VijayKumar; Byrne, Scott N.; Wolf, Peter

2016-01-01

Human skin apart from functioning as a physical barricade to stop the entry of pathogens, also hosts innumerable commensal organisms. The skin cells and the immune system constantly interact with microbes, to maintain cutaneous homeostasis, despite the challenges offered by various environmental factors. A major environmental factor affecting the skin is ultraviolet radiation (UV-R) from sunlight. UV-R is well known to modulate the immune system, which can be both beneficial and deleterious. By targeting the cells and molecules within skin, UV-R can trigger the production and release of antimicrobial peptides, affect the innate immune system and ultimately suppress the adaptive cellular immune response. This can contribute to skin carcinogenesis and the promotion of infectious agents such as herpes simplex virus and possibly others. On the other hand, a UV-established immunosuppressive environment may protect against the induction of immunologically mediated skin diseases including some of photodermatoses such as polymorphic light eruption. In this article, we share our perspective about the possibility that UV-induced immune suppression may alter the landscape of the skin’s microbiome and its components. Alternatively, or in concert with this, direct UV-induced DNA and membrane damage to the microbiome may result in pathogen associated molecular patterns (PAMPs) that interfere with UV-induced immune suppression. PMID:27559331

The skin microbiome: Is it affected by UV-induced immune suppression?

Directory of Open Access Journals (Sweden)

Vijaykumar Patra

2016-08-01

Full Text Available Human skin apart from functioning as a physical barricade to stop the entry of pathogens, also hosts innumerable commensal organisms. The skin cells and the immune system constantly interact with microbes, to maintain cutaneous homeostasis, despite the challenges offered by various environmental factors. A major environmental factor affecting the skin is ultraviolet radiation UV-R from sunlight. UV-R is well known to modulate the immune system, which can be both beneficial and deleterious. By targeting the cells and molecules within skin, UV-R can trigger the production and release of antimicrobial peptides (AMPs, affect the innate immune system and ultimately suppress the adaptive cellular immune response. This can contribute to skin carcinogenesis and the promotion of infectious agents such as herpes simplex virus and possibly others. On the other hand, a UV-established immunosuppressive environment may protect against the induction of immunologically mediated skin diseases including some of photodermatoses such as polymorphic light eruption. In this article, we share our perspective about the possibility that UV-induced immune suppression may alter the landscape of the skin's microbiome and its components. Alternatively, or in concert with this, direct UV-induced DNA and membrane damage to the microbiome may result in pathogen associated molecular patterns (PAMPs that interfere with UV-induced immune suppression.

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

Science.gov (United States)

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

2017-11-01

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

Integrated Circuit Immunity

Science.gov (United States)

Sketoe, J. G.; Clark, Anthony

2000-01-01

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

Functional characterization of viral tumor necrosis factor receptors encoded by cyprinid herpesvirus 3 (CyHV3) genome.

Science.gov (United States)

Yi, Yang; Qi, Hemei; Yuan, Jimin; Wang, Rui; Weng, Shaoping; He, Jianguo; Dong, Chuanfu

2015-08-01

Cyprinid herpesvirus 3 (CyHV3) is a large double-stranded DNA virus of Alloherpesviridae family in the order Herpesvirales. It causes significant morbidity and mortality in common carp and its ornamental koi variety, and threatens the aquaculture industries worldwide. Mimicry of cytokines and cytokine receptors is a particular strategy for large DNA viruses in modulating the host immune response. Here, we report the identification and characterization of two novel viral homologues of tumor necrosis factor receptor (TNFR) encoded by CyHV3-ORF4 and -ORF12, respectively. CyHV3-ORF4 was identified as a homologue of HVEM and CyHV3-ORF12 as a homologue of TNFRSF1. Overexpression of ORF4 and ORF12 in zebrafish embryos results in embryonic lethality, morphological defects and increased apoptosis. Although we failed to identify any interaction between the two vTNFRs and their potential ligands in zebrafish TNF superfamily by yeast two-hybrid system, the expression of some genes in TNF superfamily or TNFR superfamily were mis-regulated in ORF4 or ORF12-overexpressing embryos, especially the death receptor zHDR and its cognate ligand DL1b. Further studies showed that the apoptosis induced by the both CyHV3 vTNFRs is mainly activated through the intrinsic apoptotic pathway and requires the crosstalk between the intrinsic and extrinsic apoptotic pathway. Additionally, using RT-qPCR and Western blot assays, the expression patterns of the both vTNFRs were also analyzed during CyHV3 productive infection. Collectively, this is the first functional study of two unique vTNFRs encoded by a herpesvirus infecting non-mammalian vertebrates, which may provide novel insights into viral immune regulation mechanism and the pathogenesis of CyHV3 infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2015-03-01

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

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

Science.gov (United States)

Ilan, Yaron

2016-01-01

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

Ageing and the humoral immune response in mice

International Nuclear Information System (INIS)

Blankwater, M.J.

1978-01-01

The study presented in this thesis is concerned with changes in the humoral immune system as a function of age in different inbred mouse strains. Their capacity to develop humoral immune responses to experimentally given thymus-dependent and thymus-independent antigens under various conditions is compared. Furthermore, experiments employing thymus transplantation and thymic humoral factors which are directed at the restoration of the diminished T cell functions in old age are reported. (Auth.)

The host immune response to Clostridium difficile infection

Science.gov (United States)

2013-01-01

Clostridium difficile infection (CDI) is the most common infectious cause of healthcare-acquired diarrhoea. Outcomes of C. difficile colonization are varied, from asymptomatic carriage to fulminant colitis and death, due in part to the interplay between the pathogenic virulence factors of the bacterium and the counteractive immune responses of the host. Secreted toxins A and B are the major virulence factors of C. difficile and induce a profound inflammatory response by intoxicating intestinal epithelial cells causing proinflammatory cytokine release. Host cell necrosis, vascular permeability and neutrophil infiltration lead to an elevated white cell count, profuse diarrhoea and in severe cases, dehydration, hypoalbuminaemia and toxic megacolon. Other bacterial virulence factors, including surface layer proteins and flagella proteins, are detected by host cell surface signal molecules that trigger downstream cell-mediated immune pathways. Human studies have identified a role for serum and faecal immunoglobulin levels in protection from disease, but the recent development of a mouse model of CDI has enabled studies into the precise molecular interactions that trigger the immune response during infection. Key effector molecules have been identified that can drive towards a protective anti-inflammatory response or a damaging proinflammatory response. The limitations of current antimicrobial therapies for CDI have led to the development of both active and passive immunotherapies, none of which have, as yet been formally approved for CDI. However, recent advances in our understanding of the molecular basis of host immune protection against CDI may provide an exciting opportunity for novel therapeutic developments in the future. PMID:25165542

Immunoprophylaxis of infectious diseases in children: achievements and problems. Anti-vaccine movement as a barrier factor in immunization of the population

Directory of Open Access Journals (Sweden)

V.I. Dmytruk

2017-09-01

Full Text Available The article presents data on the state of immunization against major vaccine-controlled infections in international and regional subnational aspects. Some factors of worsening the epidemiological situation in Ukraine and the role of vaccination in the surveillance for infections that are controlled by means of specific immunoprophylaxis are identified. The features and causes of the anti-vaccine movement and possible ways of counteracting it are highlighted.

MicroRNA and cellular targets profiling reveal miR-217 and miR-576-3p as proviral factors during Oropouche infection.

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Victor Emmanuel Viana Geddes

2018-05-01

Full Text Available Oropouche Virus is the etiological agent of an arbovirus febrile disease that affects thousands of people and is widespread throughout Central and South American countries. Although isolated in 1950's, still there is scarce information regarding the virus biology and its prevalence is likely underestimated. In order to identify and elucidate interactions with host cells factors and increase the understanding about the Oropouche Virus biology, we performed microRNA (miRNA and target genes screening in human hepatocarcinoma cell line HuH-7. Cellular miRNAs are short non-coding RNAs that regulates gene expression post-transcriptionally and play key roles in several steps of viral infections. The large scale RT-qPCR based screening found 13 differentially expressed miRNAs in Oropouche infected cells. Further validation confirmed that miR-217 and miR-576-3p were 5.5 fold up-regulated at early stages of virus infection (6 hours post-infection. Using bioinformatics and pathway enrichment analysis, we predicted the cellular targets genes for miR-217 and miR-576-3p. Differential expression analysis of RNA from 95 selected targets revealed genes involved in innate immunity modulation, viral release and neurological disorder outcomes. Further analysis revealed the gene of decapping protein 2 (DCP2, a previous known restriction factor for bunyaviruses transcription, as a miR-217 candidate target that is progressively down-regulated during Oropouche infection. Our analysis also showed that activators genes involved in innate immune response through IFN-β pathway, as STING (Stimulator of Interferon Genes and TRAF3 (TNF-Receptor Associated Factor 3, were down-regulated as the infection progress. Inhibition of miR-217 or miR-576-3p restricts OROV replication, decreasing viral RNA (up to 8.3 fold and virus titer (3 fold. Finally, we showed that virus escape IFN-β mediated immune response increasing the levels of cellular miR-576-3p resulting in a decreasing of

Auditing the quality of immunization data in Tunisia

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Mohamed Kouni Chahed

2013-02-01

Full Text Available Objective: To carry out a data quality audit for the consistency and quality of immunization monitoring in Kasserine governorate in Tunisia, where immunization coverage rates more than 100%, negative dropout and conflicting coverage rates had been reported. Methods: In a randomly selected sample of 12 primary health care facilities in 2 districts all files used to record immunization data were checked to verify the accuracy of the reported 3rd dose of diphtheriatetanus-pertussis vaccine during a calendar year. Results: The results found frequent overreporting or under-reporting of doses being administrated in all health facilities. The regional verification factor was estimated as 85% and quality index was 55%. Conclusions: Data quality audit provides a effective tool for self-assessment implementation and developing a critical analysis of the quality of routine immunization data at all levels of health service.

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

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Fei Jiang

Full Text Available 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.

Met1-linked Ubiquitination in Immune Signalling

DEFF Research Database (Denmark)

Fiil, Berthe Katrine; Gyrd-Hansen, Mads

2014-01-01

Methionine 1-linked ubiquitin chains (Met1-Ub), or linear ubiquitin, has emerged as a central post-translational modification in innate immune signalling. Molecular machinery that assembles, senses and, more recently, disassembles Met1-Ub has been identified, and technical advances have enabled...... identification of physiological substrates for Met1-Ub in response to activation of innate immune receptors. These discoveries have significantly advanced our understanding of how non-degradative ubiquitin modifications control pro-inflammatory responses mediated by nuclear factor κB and mitogen...

Modulation of immune responses in stress by Yoga

Directory of Open Access Journals (Sweden)

Arora Sarika

2008-01-01

Full Text Available Stress is a constant factor in today′s fastpaced life that can jeopardize our health if left unchecked. It is only in the last half century that the role of stress in every ailment from the common cold to AIDS has been emphasized, and the mechanisms involved in this process have been studied. Stress influences the immune response presumably through the activation of the hypothalamic-pituitary adrenal axis, hypothalamic pituitary-gonadal axis, and the sympathetic-adrenal-medullary system. Various neurotransmitters, neuropeptides, hormones, and cytokines mediate these complex bidirectional interactions between the central nervous system (CNS and the immune system. The effects of stress on the immune responses result in alterations in the number of immune cells and cytokine dysregulation. Various stress management strategies such as meditation, yoga, hypnosis, and muscle relaxation have been shown to reduce the psychological and physiological effects of stress in cancers and HIV infection. This review aims to discuss the effect of stress on the immune system and examine how relaxation techniques such as Yoga and meditation could regulate the cytokine levels and hence, the immune responses during stress.

Regulation of intestinal homeostasis by innate and adaptive immunity.

Science.gov (United States)

Kayama, Hisako; Takeda, Kiyoshi

2012-11-01

The intestine is a unique tissue where an elaborate balance is maintained between tolerance and immune responses against a variety of environmental factors such as food and the microflora. In a healthy individual, the microflora stimulates innate and adaptive immune systems to maintain gut homeostasis. However, the interaction of environmental factors with particular genetic backgrounds can lead to dramatic changes in the composition of the microflora (i.e. dysbiosis). Many of the specific commensal-bacterial products and the signaling pathways they trigger have been characterized. The role of T(h)1, T(h)2 and T(h)17 cells in inflammatory bowel disease has been widely investigated, as has the contribution of epithelial cells and subsets of dendritic cells and macrophages. To date, multiple regulatory cells in adaptive immunity, such as regulatory T cells and regulatory B cells, have been shown to maintain gut homeostasis by preventing inappropriate innate and adaptive immune responses to commensal bacteria. Additionally, regulatory myeloid cells have recently been identified that prevent intestinal inflammation by inhibiting T-cell proliferation. An increasing body of evidence has shown that multiple regulatory mechanisms contribute to the maintenance of gut homeostasis.

Factors associated with differential uptake of seasonal influenza immunizations among underserved communities during the 2009-2010 influenza season.

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Vlahov, David; Bond, Keosha T; Jones, Kandice C; Ompad, Danielle C

2012-04-01

Influenza vaccination coverage remains low and disparities persist. In New York City, a community-based participatory research project (Project VIVA) worked to address this issue in Harlem and the South Bronx by supplementing existing vaccination programs with non-traditional venues (i.e., community-based organizations). We conducted a 10 min survey to assess access to influenza vaccine as well as attitudes and beliefs towards influenza vaccination that could inform intervention development for subsequent seasons. Among 991 participants recruited using street intercept techniques, 63% received seasonal vaccine only, 11% seasonal and H1N1, and 26% neither; 89% reported seeing a health care provider (HCP) during the influenza season. Correlates of immunization among those with provider visits during the influenza season included being US-born, interest in getting the vaccine, concern about self or family getting influenza, an HCP's recommendation and comfort with government. Among those without an HCP visit, factors associated with immunization included being US born, married, interest in getting the vaccine, understanding influenza information, and concern about getting influenza. Factors associated with lack of interest in influenza vaccine included being born outside the US, Black and uncomfortable with government. In medically underserved areas, having access to routine medical care and understanding the medical implications of influenza play an important role in enhancing uptake of seasonal influenza vaccination. Strategies to improve vaccination rates among Blacks and foreign-born residents need to be addressed. The use of non-traditional venues to provide influenza vaccinations in underserved communities has the potential to reduce health disparities.

Obesity, Fat Mass and Immune System: Role for Leptin

Directory of Open Access Journals (Sweden)

Vera Francisco

2018-06-01

Full Text Available Obesity is an epidemic disease characterized by chronic low-grade inflammation associated with a dysfunctional fat mass. Adipose tissue is now considered an extremely active endocrine organ that secretes cytokine-like hormones, called adipokines, either pro- or anti-inflammatory factors bridging metabolism to the immune system. Leptin is historically one of most relevant adipokines, with important physiological roles in the central control of energy metabolism and in the regulation of metabolism-immune system interplay, being a cornerstone of the emerging field of immunometabolism. Indeed, leptin receptor is expressed throughout the immune system and leptin has been shown to regulate both innate and adaptive immune responses. This review discusses the latest data regarding the role of leptin as a mediator of immune system and metabolism, with particular emphasis on its effects on obesity-associated metabolic disorders and autoimmune and/or inflammatory rheumatic diseases.

The role of innate signaling in the homeostasis of tolerance and immunity in the intestine.

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Wells, Jerry M; Loonen, Linda M P; Karczewski, Jurgen M

2010-01-01

In the intestine innate recognition of microbes is achieved through pattern recognition receptor (PRR) families expressed in immune cells and different cell lineages of the intestinal epithelium. Toll-like receptor (TLR) and nucleotide-binding and oligomerization domain-like receptor (NLR) families are emerging as key mediators of immunity through their role as maturation factors of immune cells and triggers for the production of cytokines and chemokines and antimicrobial factors. At the mucosal surface chronic activation of the immune system is avoided through the epithelial production of a glycocalyx, steady-state production of antimicrobial factors as well as the selective expression and localization of PRRs. Additionally, the polarization of epithelial TLR signaling and suppression of NF-kappaB activation by luminal commensals appears to contribute to the homeostasis of tolerance and immunity. Several studies have demonstrated that TLR signaling in epithelial cells contributes to a range of homeostatic mechanisms including proliferation, wound healing, epithelial integrity, and regulation of mucosal immune functions. The intestinal epithelium appears to have uniquely evolved to maintain mucosal tolerance and immunity, and future efforts to further understand the molecular mechanisms of intestinal homeostasis may have a major impact on human health. Copyright 2009 Elsevier GmbH. All rights reserved.

The interaction between the iron-responsive element binding protein and its cognate RNA is highly dependent upon both RNA sequence and structure.

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Jaffrey, S R; Haile, D J; Klausner, R D; Harford, J B

1993-09-25

To assess the influence of RNA sequence/structure on the interaction RNAs with the iron-responsive element binding protein (IRE-BP), twenty eight altered RNAs were tested as competitors for an RNA corresponding to the ferritin H chain IRE. All changes in the loop of the predicted IRE hairpin and in the unpaired cytosine residue characteristically found in IRE stems significantly decreased the apparent affinity of the RNA for the IRE-BP. Similarly, alteration in the spacing and/or orientation of the loop and the unpaired cytosine of the stem by either increasing or decreasing the number of base pairs separating them significantly reduced efficacy as a competitor. It is inferred that the IRE-BP forms multiple contacts with its cognate RNA, and that these contacts, acting in concert, provide the basis for the high affinity of this interaction.

Nucleic acid-induced antiviral immunity in invertebrates: an evolutionary perspective.

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Wang, Pei-Hui; Weng, Shao-Ping; He, Jian-Guo

2015-02-01

Nucleic acids derived from viral pathogens are typical pathogen associated molecular patterns (PAMPs). In mammals, the recognition of viral nucleic acids by pattern recognition receptors (PRRs), which include Toll-like receptors (TLRs) and retinoic acid-inducible gene (RIG)-I-like receptors (RLRs), induces the release of inflammatory cytokines and type I interferons (IFNs) through the activation of nuclear factor κB (NF-κB) and interferon regulatory factor (IRF) 3/7 pathways, triggering the host antiviral state. However, whether nucleic acids can induce similar antiviral immunity in invertebrates remains ambiguous. Several studies have reported that nucleic acid mimics, especially dsRNA mimic poly(I:C), can strongly induce non-specific antiviral immune responses in insects, shrimp, and oyster. This behavior shows multiple similarities to the hallmarks of mammalian IFN responses. In this review, we highlight the current understanding of nucleic acid-induced antiviral immunity in invertebrates. We also discuss the potential recognition and regulatory mechanisms that confer non-specific antiviral immunity on invertebrate hosts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Transcriptional profiling provides insights into metronomic cyclophosphamide-activated, innate immune-dependent regression of brain tumor xenografts

International Nuclear Information System (INIS)

Doloff, Joshua C; Waxman, David J

2015-01-01

Cyclophosphamide treatment on a six-day repeating metronomic schedule induces a dramatic, innate immune cell-dependent regression of implanted gliomas. However, little is known about the underlying mechanisms whereby metronomic cyclophosphamide induces innate immune cell mobilization and recruitment, or about the role of DNA damage and cell stress response pathways in eliciting the immune responses linked to tumor regression. Untreated and metronomic cyclophosphamide-treated human U251 glioblastoma xenografts were analyzed on human microarrays at two treatment time points to identify responsive tumor cell-specific factors and their upstream regulators. Mouse microarray analysis across two glioma models (human U251, rat 9L) was used to identify host factors and gene networks that contribute to the observed immune and tumor regression responses. Metronomic cyclophosphamide increased expression of tumor cell-derived DNA damage, cell stress, and cell death genes, which may facilitate innate immune activation. Increased expression of many host (mouse) immune networks was also seen in both tumor models, including complement components, toll-like receptors, interferons, and cytolysis pathways. Key upstream regulators activated by metronomic cyclophosphamide include members of the interferon, toll-like receptor, inflammatory response, and PPAR signaling pathways, whose activation may contribute to anti-tumor immunity. Many upstream regulators inhibited by metronomic cyclophosphamide, including hypoxia-inducible factors and MAP kinases, have glioma-promoting activity; their inhibition may contribute to the therapeutic effectiveness of the six-day repeating metronomic cyclophosphamide schedule. Large numbers of responsive cytokines, chemokines and immune regulatory genes linked to innate immune cell recruitment and tumor regression were identified, as were several immunosuppressive factors that may contribute to the observed escape of some tumors from metronomic CPA

Adaptation in the innate immune system and heterologous innate immunity.

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Martin, Stefan F

2014-11-01

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

Immune suppressor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells

International Nuclear Information System (INIS)

Nakajima, Hideaki; Shibata, Fumi; Fukuchi, Yumi; Goto-Koshino, Yuko; Ito, Miyuki; Urano, Atsushi; Nakahata, Tatsutoshi; Aburatani, Hiroyuki; Kitamura, Toshio

2006-01-01

Immune suppressor factor (ISF) is a subunit of the vacuolar ATPase proton pump. We earlier identified a short form of ISF (ShIF) as a stroma-derived factor that supports cytokine-independent growth of mutant Ba/F3 cells. Here, we report that ISF/ShIF supports self-renewal and expansion of primary hematopoietic stem cells (HSCs). Co-culture of murine bone marrow cells with a stromal cell line overexpressing ISF or ShIF (MS10/ISF or MS10/ShIF) not only enhanced their colony-forming activity and the numbers of long-term culture initiating cells, but also maintained the competitive repopulating activity of HSC. This stem cell supporting activity depended on the proton-transfer function of ISF/ShIF. Gene expression analysis of ISF/ShIF-transfected cell lines revealed down-regulation of secreted frizzled-related protein-1 and tissue inhibitor of metalloproteinase-3, and the restoration of their expressions in MS10/ISF cells partially reversed its enhanced LTC-IC supporting activity to a normal level. These results suggest that ISF/ShIF confers stromal cells with enhanced supporting activities for HSCs by modulating Wnt-activity and the extracellular matrix

The role of immune mechanisms in Tourette syndrome.

Science.gov (United States)

Martino, Davide; Zis, Panagiotis; Buttiglione, Maura

2015-08-18

Tourette syndrome (TS) is a childhood-onset tic disorder associated with abnormal development of brain networks involved in the sensory and motor processing. An involvement of immune mechanisms in its pathophysiology has been proposed. Animal models based on active immunization with bacterial or viral mimics, direct injection of cytokines or patients' serum anti-neuronal antibodies, and transgenic approaches replicated stereotyped behaviors observed in human TS. A crucial role of microglia in the neural-immune crosstalk within TS and related disorders has been proposed by animal models and confirmed by recent post mortem studies. With analogy to autism, genetic and early life environmental factors could foster the involvement of immune mechanisms to the abnormal developmental trajectories postulated in TS, as well as lead to systemic immune dysregulation in this condition. Clinical studies demonstrate an association between TS and immune responses to pathogens like group A Streptococcus (GAS), although their role as risk-modifiers is still undefined. Overactivity of immune responses at a systemic level is suggested by clinical studies exploring cytokine and immunoglobulin levels, immune cell subpopulations, and gene expression profiling of peripheral lymphocytes. The involvement of autoantibodies, on the other hand, remains uncertain and warrants more work using live cell-based approaches. Overall, a body of evidence supports the hypothesis that disease mechanisms in TS, like other neurodevelopmental illnesses (e.g. autism), may involve dysfunctional neural-immune cross-talk, ultimately leading to altered maturation of brain pathways controlling different behavioral domains and, possibly, differences in organising immune and stress responses. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

Factors that influence parental vaccination decisions for adolescents, 13 to 17 years old: National Immunization Survey-Teen, 2010.

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Dorell, Christina; Yankey, David; Kennedy, Allison; Stokley, Shannon

2013-02-01

We aim to describe factors that influence parental decisions to vaccinate their adolescents. Data from the July to December 2010 National Immunization Survey-Teen Parental Concerns Module were analyzed to determine factors that influence parental decisions to vaccinate their adolescents. Parents reported that their adolescent's health care provider recommended tetanus toxoid/tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Td/Tdap; 74.4%), meningococcal conjugate (MenACWY; 60.3%), and human papillomavirus (HPV; 71.3%). Vaccination coverage estimates were significantly higher among parents who reported receiving a provider recommendation: 85.2% versus 76.7% (Td/Tdap), 77.3% versus 49.7% (MenACWY), and 62.2% versus 21.5% (HPV). Compared with Td/Tdap and MenACWY, fewer HPV vaccination conversations included recommendations for vaccination. Other than health care providers, school requirements (46.1%), news coverage (31.2%), and family (31.0%) were most frequently reported influences on parental vaccination decisions. Many factors influence parental decisions to vaccinate their adolescents; one of the most important factors is the provider recommendation. Missed opportunities for vaccination persist when strong vaccination recommendations are not given or are delayed.

T cell immunity

OpenAIRE

Emel Bülbül Başkan

2013-01-01

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

Radioresistance of immunized animals in internal irradiation

International Nuclear Information System (INIS)

Kal'nitskij, S.A.; Ponomareva, T.V.; Shubik, V.M.

1981-01-01

The influence of an immunization with bacterial vaccines and antimeasles-gamma-globulin on the radioresistance of raceless white mice was studied. In the vaccinated animals a higher survival rate and duration of life, a better general condition and a better curve of weight and stronger physical stamina were stated compared to the merely irradiated mice. The higher radioresistance is ascribed to the stimulation of cellular and humoral factors of the unspecific protection against infection, to the repair of the lymphoid tissue of the immunized animals and to the decrease in autosensibilization. (author)

Parental care improves immunity in the seahorse (Hippocampus erectus).

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Lin, Tingting; Zhang, Dong; Liu, Xin; Xiao, Dongxue

2016-11-01

In the present study, the sexual dimorphism in immune response in the seahorse Hippocampus erectus in which males compete for mates and invest heavily in parental care was assessed. Variability in immunocompetence in virginal seahorses with differing levels of sexual maturity (i.e., immaturity, early maturity and maturity) and with different mating statuses (i.e., virginal, experienced mating failure and experienced mating success) were analyzed by evaluating immune parameters in the plasma. Additionally, ultrastructural characteristics of the inner epithelium of the brood pouch were compared between males that had experienced mating failure and those that had succeeded. Generally, immunity in sexually mature virgin males was greater than in females, and mating competition significantly reduced males' immunity. However, parental care gave males stronger immune and metabolic abilities and resulted in their immunity significantly rebounding after a successful mating. The present study quantitatively clarifies, for the first time, how parental care and mating competition jointly affect immunity. Moreover, previous findings that females display more efficient immune defenses than males in conventional species (i.e., males are as competitor and females as care giver) and that males' immunity is higher than females' in the pipefish (i.e., females are as competitor and males as care giver) in combination with the present results indicate that parental care is a key factor for sexual dimorphism in immunity. The care-giving sex has strong immunity regardless of the sex in charge of mating competition or not. Copyright © 2016 Elsevier Ltd. All rights reserved.

Full trans-activation mediated by the immediate-early protein of equine herpesvirus 1 requires a consensus TATA box, but not its cognate binding sequence.

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Kim, Seong K; Shakya, Akhalesh K; O'Callaghan, Dennis J

2016-01-04

The immediate-early protein (IEP) of equine herpesvirus 1 (EHV-1) has extensive homology to the IEP of alphaherpesviruses and possesses domains essential for trans-activation, including an acidic trans-activation domain (TAD) and binding domains for DNA, TFIIB, and TBP. Our data showed that the IEP directly interacted with transcription factor TFIIA, which is known to stabilize the binding of TBP and TFIID to the TATA box of core promoters. When the TATA box of the EICP0 promoter was mutated to a nonfunctional TATA box, IEP-mediated trans-activation was reduced from 22-fold to 7-fold. The IEP trans-activated the viral promoters in a TATA motif-dependent manner. Our previous data showed that the IEP is able to repress its own promoter when the IEP-binding sequence (IEBS) is located within 26-bp from the TATA box. When the IEBS was located at 100 bp upstream of the TATA box, IEP-mediated trans-activation was very similar to that of the minimal IE(nt -89 to +73) promoter lacking the IEBS. As the distance from the IEBS to the TATA box decreased, IEP-mediated trans-activation progressively decreased, indicating that the IEBS located within 100 bp from the TATA box sequence functions as a distance-dependent repressive element. These results indicated that IEP-mediated full trans-activation requires a consensus TATA box of core promoters, but not its binding to the cognate sequence (IEBS). Copyright © 2015 Elsevier B.V. All rights reserved.

Full trans–activation mediated by the immediate–early protein of equine herpesvirus 1 requires a consensus TATA box, but not its cognate binding sequence

Science.gov (United States)

Kim, Seong K.; Shakya, Akhalesh K.; O'Callaghan, Dennis J.

2015-01-01

The immediate-early protein (IEP) of equine herpesvirus 1 (EHV-1) has extensive homology to the IEP of alphaherpesviruses and possesses domains essential for trans-activation, including an acidic trans-activation domain (TAD) and binding domains for DNA, TFIIB, and TBP. Our data showed that the IEP directly interacted with transcription factor TFIIA, which is known to stabilize the binding of TBP and TFIID to the TATA box of core promoters. When the TATA box of the EICP0 promoter was mutated to a nonfunctional TATA box, IEP-mediated trans-activation was reduced from 22-fold to 7-fold. The IEP trans-activated the viral promoters in a TATA motif-dependent manner. Our previous data showed that the IEP is able to repress its own promoter when the IEP-binding sequence (IEBS) is located within 26-bp from the TATA box. When the IEBS was located at 100 bp upstream of the TATA box, IEP-mediated trans-activation was very similar to that of the minimal IE(nt −89 to +73) promoter lacking the IEBS. As the distance from the IEBS to the TATA box decreased, IEP-mediated trans-activation progressively decreased, indicating that the IEBS located within 100 bp from the TATA box sequence functions as a distance-dependent repressive element. These results indicated that IEP-mediated full trans-activation requires a consensus TATA box of core promoters, but not its binding to the cognate sequence (IEBS). PMID:26541315

Posttransplant Immune Activation: Innocent Bystander or Insidious Culprit of Posttransplant Accelerated Atherosclerosis.

Science.gov (United States)

Ducloux, Didier; Bamoulid, Jamal; Crepin, Thomas; Rebibou, Jean-Michel; Courivaud, Cecile; Saas, Philippe

2017-09-01

Cardiovascular disease is a major cause of morbidity, disability, and mortality in kidney transplant patients. Cumulative reports indicate that the excessive risk of cardiovascular events is not entirely explained by the increased prevalence of traditional cardiovascular risk factors. Atherosclerosis is a chronic inflammatory disease, and it has been postulated that posttransplant immune disturbances may explain the gap between the predicted and observed risks of cardiovascular events. Although concordant data suggest that innate immunity contributes to the posttransplant accelerated atherosclerosis, only few arguments plead for a role of adaptive immunity. We report and discuss here consistent data demonstrating that CD8 + T cell activation is a frequent posttransplant immune feature that may have pro-atherogenic effects. Expansion of exhausted/activated CD8 + T cells in kidney transplant recipients is stimulated by several factors including cytomegalovirus infections, lymphodepletive therapy (e.g., antithymocyte globulins), chronic allogeneic stimulation, and a past history of renal insufficiency. This is observed in the setting of decreased thymic activity, a process also found in elderly individuals and reflecting accelerated immune senescence.

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

Directory of Open Access Journals (Sweden)

Nath KD

2013-12-01

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

Immune mechanisms in fish skin against monogeneans--a model.

Science.gov (United States)

Buchmann, K

1999-01-01

Host responses against skin inhabiting monogeneans are commonly observed but the responsible immune mechanisms in the fish skin are sufficiently described. Based on recent knowledge of fish immunity and skin response mechanisms in mammals a model for the skin immunity in fish to monogenean infections is proposed. Important cellular components of the model are the epithelial cells, the mucous cells and leucocytes. The release of cytokines, e.g., IL-1, following mechanical or chemical injury of the epithelial cells, initiates a series of events leading to decrease of the ectoparasite population. Cytokines (e.g., IL-1, TNF, INF) are suggested to affect secretions from mucous cell and attract neutrophils and macrophages. Leukotrienes are probably involved in the inflammatory reactions. The subsequent production of humoral substances (among others complement factors and peptides) could be responsible for the antiparasitic response in the later stages of infection. Although non-specific factors dominate the response, the involvement of specific antibodies and lymphocytes cannot be excluded.

Effector-triggered immunity: from pathogen perception to robust defense.

Science.gov (United States)

Cui, Haitao; Tsuda, Kenichi; Parker, Jane E

2015-01-01

In plant innate immunity, individual cells have the capacity to sense and respond to pathogen attack. Intracellular recognition mechanisms have evolved to intercept perturbations by pathogen virulence factors (effectors) early in host infection and convert it to rapid defense. One key to resistance success is a polymorphic family of intracellular nucleotide-binding/leucine-rich-repeat (NLR) receptors that detect effector interference in different parts of the cell. Effector-activated NLRs connect, in various ways, to a conserved basal resistance network in order to transcriptionally boost defense programs. Effector-triggered immunity displays remarkable robustness against pathogen disturbance, in part by employing compensatory mechanisms within the defense network. Also, the mobility of some NLRs and coordination of resistance pathways across cell compartments provides flexibility to fine-tune immune outputs. Furthermore, a number of NLRs function close to the nuclear chromatin by balancing actions of defense-repressing and defense-activating transcription factors to program cells dynamically for effective disease resistance.

Impact of the raising immunizations safely and effectively (RISE) program on healthcare worker influenza immunization rates in long term care settings.

Science.gov (United States)

Nace, David A; Handler, Steven M; Hoffman, Erika L; Perera, Subashan

2012-11-01

National influenza immunization rates for healthcare workers (HCW) in long-term care (LTC) remain unacceptably low. This poses a serious public health threat to residents. Prior work has suggested high staff turnover rates as a contributing factor to low immunization rates. There is a critical need to identify and deploy successful models of HCW influenza immunization programs to LTC facilities. This report describes one potential model that has been successfully initiated in a network of LTC facilities. All facilities served by a single regional LTC pharmacy were invited to participate in a HCW influenza immunization program. This voluntary immunization program began in 2005 and continues to the present. As part of the program, the pharmacy promoted organizational change by assuming oversight and control of HCW immunization policies and processes for all facilities. Primary and secondary outcomes are the number of facilities reaching HCW influenza immunization rates of 60% and 80%. Fourteen of the 16 LTC facilities participated. Facilities were diverse and included both nursing and assisted living facilities; unionized and nonunionized facilities; and urban, suburban, and rural facilities. The pharmacy provided educational and communication materials, centralized data collection using a standardized definition for HCW immunization rates, and facility feedback. All 14 LTC facilities achieved the primary goal of 60% and nearly two thirds reached the secondary goal of 80%. Twenty percent reached the new Healthy People 2020 goal of 90%. It is possible for LTC facilities to improve HCW immunization rates using a pharmacy based, voluntary HCW influenza immunization approach. Such an approach may help attenuate the negative influence of staff turnover on HCW immunizations. Attainment of the new Health People 2020 goals still remains a challenge and may require mandatory programs. Copyright © 2012 American Medical Directors Association, Inc. Published by Elsevier Inc

Tailoring the Immune Response via Customization of Pathogen Gene Expression.

Science.gov (United States)

Runco, Lisa M; Stauft, Charles B; Coleman, J Robert

2014-01-01

The majority of studies focused on the construction and reengineering of bacterial pathogens have mainly relied on the knocking out of virulence factors or deletion/mutation of amino acid residues to then observe the microbe's phenotype and the resulting effect on the host immune response. These knockout bacterial strains have also been proposed as vaccines to combat bacterial disease. Theoretically, knockout strains would be unable to cause disease since their virulence factors have been removed, yet they could induce a protective memory response. While knockout strains have been valuable tools to discern the role of virulence factors in host immunity and bacterial pathogenesis, they have been unable to yield clinically relevant vaccines. The advent of synthetic biology and enhanced user-directed gene customization has altered this binary process of knockout, followed by observation. Recent studies have shown that a researcher can now tailor and customize a given microbe's gene expression to produce a desired immune response. In this commentary, we highlight these studies as a new avenue for controlling the inflammatory response as well as vaccine development.

A review of the immune molecules in the sea cucumber.

Science.gov (United States)

Xue, Zhuang; Li, Hui; Wang, Xiuli; Li, Xia; Liu, Yang; Sun, Jing; Liu, Cenjie

2015-05-01

It is very important to identify and characterize the immune-related genes that respond to pathogens. Until recently, only some of the immune-related genes in sea cucumbers had been characterized. Their expression patterns after pathogen challenges have been analyzed via expressed sequence tag libraries, microarray studies and proteomic approaches. These genes include lectins, antimicrobial peptides, lysozyme, enzymes, clotting protein, pattern recognition proteins, Toll receptors, complement C3 and other humoral factors that might participate in the innate immune system of sea cucumbers. Although the participation of some of these immune molecules in the sea cucumber's innate immune defense against invading pathogens has been demonstrated, the functions of many of the molecules remain unclear. This review focuses on the discovery and functional characterization of the immune-related molecules from the sea cucumber for the first time and provides new insights into the immune mechanisms of the sea cucumber, which opens new possibilities for developing drugs for novel anti-bacterial and antiviral applications in fisheries. Copyright © 2015 Elsevier Ltd. All rights reserved.

Measuring polio immunity to plan immunization activities.

Science.gov (United States)

Voorman, Arend; Lyons, Hil M

2016-11-21

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

Polyphenol Compound as a Transcription Factor Inhibitor.

Science.gov (United States)

Park, Seyeon

2015-10-30

A target-based approach has been used to develop novel drugs in many therapeutic fields. In the final stage of intracellular signaling, transcription factor-DNA interactions are central to most biological processes and therefore represent a large and important class of targets for human therapeutics. Thus, we focused on the idea that the disruption of protein dimers and cognate DNA complexes could impair the transcriptional activation and cell transformation regulated by these proteins. Historically, natural products have been regarded as providing the primary leading compounds capable of modulating protein-protein or protein-DNA interactions. Although their mechanism of action is not fully defined, polyphenols including flavonoids were found to act mostly as site-directed small molecule inhibitors on signaling. There are many reports in the literature of screening initiatives suggesting improved drugs that can modulate the transcription factor interactions responsible for disease. In this review, we focus on polyphenol compound inhibitors against dimeric forms of transcription factor components of intracellular signaling pathways (for instance, c-jun/c-fos (Activator Protein-1; AP-1), c-myc/max, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and β-catenin/T cell factor (Tcf)).

They Are What You Eat: Can Nutritional Factors during Gestation and Early Infancy Modulate the Neonatal Immune Response?

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Sarah Prentice

2017-11-01

Full Text Available The ontogeny of the human immune system is sensitive to nutrition even in the very early embryo, with both deficiency and excess of macro- and micronutrients being potentially detrimental. Neonates are particularly vulnerable to infectious disease due to the immaturity of the immune system and modulation of nutritional immunity may play a role in this sensitivity. This review examines whether nutrition around the time of conception, throughout pregnancy, and in early neonatal life may impact on the developing infant immune system.

Humoral immune response to measles and varicella vaccination in former very low birth weight preterm infants

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Carolina Schlindwein Mariano Ferreira; Maria Cristina Abrão Aued Perin; Maria Isabel de Moraes-Pinto; Raquel Maria Simão-Gurge; Ana Lucia Goulart; Lily Yin Weckx; Amélia Miyashiro Nunes dos Santos

2018-01-01

Introduction: Immune response to vaccination in infants born prematurely may be lower than in infants born at full-term. Some clinical factors might be associated with humoral immune response. Objectives: The objectives of this study were to compare the immune response to measles and varicella vaccination in infants born prematurely with those born at full-term and to analyze factors associated with measles and varicella antibody levels. Methods: Prospective study including two groups o...

IMMUNIZATION COVERAGE IN ETAWAH: A BORDER DISTRICT OF UTTAR PRADESH

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C M Singh

2012-06-01

Full Text Available Research question: What is the coverage of immunization among children of 12-23 months age group in rural Etawah (a border District of Uttar Pradesh? Objectives: 1. To assess the immunization coverage among 12-23 months age group children in rural Etawah. 2. To study the association of different socio-demographic factors with utilization of immunization services. Study Design: A community based cross sectional study. Setting: The present study was conducted in Saifai Block of District Etawah. Participants: Two hundred and ten children of 12-23 months were included in the study. Results: The percentage of completely immunized children was found to be 40%. The present study revealed that approximately 79.0% children were immunized against BCG, while the corresponding figure for measles vaccination was just 42.4%. Drop-out rate for complete immunization was 48.1%. Conclusion: Overall coverage of immunization services among children aged 12-23 months was lower than the national figures for rural Etawah. Literacy status of parents was significantly associated with the percentage of fully immunized children and the drop-out rate was also found to be higher among children of illiterate mothers. So there is need and scope of more focused Information, education and communication efforts towards parents regarding immunization services.

IMMUNIZATION COVERAGE IN ETAWAH: A BORDER DISTRICT OF UTTAR PRADESH

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C M Singh

2012-07-01

Full Text Available Research question: What is the coverage of immunization among children of 12-23 months age group in rural Etawah (a border District of Uttar Pradesh? Objectives: 1. To assess the immunization coverage among 12-23 months age group children in rural Etawah. 2. To study the association of different socio-demographic factors with utilization of immunization services. Study Design: A community based cross sectional study. Setting: The present study was conducted in Saifai Block of District Etawah. Participants: Two hundred and ten children of 12-23 months were included in the study. Results: The percentage of completely immunized children was found to be 40%. The present study revealed that approximately 79.0% children were immunized against BCG, while the corresponding figure for measles vaccination was just 42.4%. Drop-out rate for complete immunization was 48.1%. Conclusion: Overall coverage of immunization services among children aged 12-23 months was lower than the national figures for rural Etawah. Literacy status of parents was significantly associated with the percentage of fully immunized children and the drop-out rate was also found to be higher among children of illiterate mothers. So there is need and scope of more focused Information, education and communication efforts towards parents regarding immunization services.

Immunizations challenge healthcare personnel and affects immunization rates.

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Strohfus, Pamela K; Kim, Susan C; Palma, Sara; Duke, Russell A; Remington, Richard; Roberts, Caleb

2017-02-01

This study measured 1. medical office immunization rates and 2. health care personnel competency in managing vaccine practices before and after evidence-based immunization education was provided. This descriptive study compared 32 family medicine and pediatric offices and 178 medical assistants, licensed practical nurses, registered nurses, nurse practitioners, and physicians in knowledge-based testing pre-education, post-education, and 12-months post-education. Immunization rates were assessed before and 18-months post-education. Immunization rates increased 10.3% - 18months post-education; knowledge increased 7.8% - 12months post-education. Family medicine offices, licensed practical nurses, and medical assistants showed significant knowledge deficits before and 12-months post-education. All demographic groups scored less in storage/handling 12-months post-education. This study is one of the first studies to identify competency challenges in effective immunization delivery among medical assistants, licensed practical nurses, and family medicine offices. Formal and continuous education in immunization administration and storage/handling is recommended among these select groups. Copyright © 2016 Elsevier Inc. All rights reserved.

Accelerated aging versus rejuvenation of the immune system in heterochronic parabiosis.

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Pishel, Iryna; Shytikov, Dmytro; Orlova, Tatiana; Peregudov, Alex; Artyuhov, Igor; Butenko, Gennadij

2012-04-01

The emergence of immune disorders in aging is explained by many factors, including thymus dysfunction, decrease in the proportion and function of naïve T cells, and so forth. There are several approaches to preventing these changes, such as thymus rejuvenation, stem cells recovery, modulation of hormone production, and others. Our investigations of heterochronic parabiosis have shown that benefits of a young immune system, e.g., actively working thymus and regular migration of young hematopoietic stem cells between parabiotic partners, appeared unable to restore the immune system of the old partner. At the same time, we have established a progressive immune impairment in the young heterochronic partners. The mechanism of age changes in the immune system in this model, which may lead to reduced life expectancy, has not been fully understood. The first age-related manifestation in the young partners observed 3 weeks after the surgery was a dramatic increase of CD8(+)44(+) cells population in the spleen. A detailed analysis of further changes revealed a progressive decline of most immunological functions observable for up to 3 months after the surgery. This article reviews possible mechanisms of induction of age-related changes in the immune system of young heterochronic partners. The data obtained suggest the existence of certain factors in the old organisms that trigger aging, thus preventing the rejuvenation process.

Tumor-Derived Exosomes and Their Role in Tumor-Induced Immune Suppression

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Theresa L. Whiteside

2016-10-01

Full Text Available Tumor-derived exosomes (TEX are emerging as critical components of an intercellular information network between the tumor and the host. The tumor escapes from the host immune system by using a variety of mechanisms designed to impair or eliminate anti-tumor immunity. TEX carrying a cargo of immunoinhibitory molecules and factors represent one such mechanism. TEX, which are present in all body fluids of cancer patients, deliver negative molecular or genetic signals to immune cells re-programming their functions. Although TEX can also stimulate immune activity, in the microenvironments dominated by the tumor, TEX tend to mediate immune suppression thus promoting tumor progression. The TEX content, in part resembling that of the parent cell, may serve as a source of cancer biomarkers. TEX also interfere with immune therapies. A better understanding of TEX and their contribution to cancer progression and cancer patients’ response to immune therapies represents a challenging new field of investigation.

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.

The Immune System in Irritable Bowel Syndrome

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Cremon, Cesare; Carini, Giovanni; Bellacosa, Lara; Zecchi, Lisa; De Giorgio, Roberto; Corinaldesi, Roberto; Stanghellini, Vincenzo

2011-01-01

The potential relevance of systemic and gastrointestinal immune activation in the pathophysiology and symptom generation in the irritable bowel syndrome (IBS) is supported by a number of observations. Infectious gastroenteritis is the strongest risk factor for the development of IBS and increased rates of IBS-like symptoms have been detected in patients with inflammatory bowel disease in remission or in celiac disease patients on a gluten free diet. The number of T cells and mast cells in the small and large intestine of patients with IBS is increased in a large proportion of patients with IBS over healthy controls. Mediators released by immune cells and likely from other non-immune competent cells impact on the function of enteric and sensory afferent nerves as well as on epithelial tight junctions controlling mucosal barrier of recipient animals, isolated human gut tissues or cell culture systems. Antibodies against microbiota antigens (bacterial flagellin), and increased levels of cytokines have been detected systemically in the peripheral blood advocating the existence of abnormal host-microbial interactions and systemic immune responses. Nonetheless, there is wide overlap of data obtained in healthy controls; in addition, the subsets of patients showing immune activation have yet to be clearly identified. Gender, age, geographic differences, genetic predisposition, diet and differences in the intestinal microbiota likely play a role and further research has to be done to clarify their relevance as potential mechanisms in the described immune system dysregulation. Immune activation has stimulated interest for the potential identification of biomarkers useful for clinical and research purposes and the development of novel therapeutic approaches. PMID:22148103

Immunization

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

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

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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.

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

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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.

Neurotrophin Receptor p75NTR Regulates Immune Function of Plasmacytoid Dendritic Cells.

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Bandoła, Joanna; Richter, Cornelia; Ryser, Martin; Jamal, Arshad; Ashton, Michelle P; von Bonin, Malte; Kuhn, Matthias; Dorschner, Benjamin; Alexopoulou, Dimitra; Navratiel, Katrin; Roeder, Ingo; Dahl, Andreas; Hedrich, Christian M; Bonifacio, Ezio; Brenner, Sebastian; Thieme, Sebastian

2017-01-01

Plasmacytoid dendritic cells (pDCs) regulate innate and adaptive immunity. Neurotrophins and their receptors control the function of neuronal tissue. In addition, they have been demonstrated to be part of the immune response but little is known about the effector immune cells involved. We report, for the first time, the expression and immune-regulatory function of the low affinity neurotrophin receptor p75 neurotrophin receptor (p75NTR) by the antigen-presenting pDCs, mediated by toll-like receptor (TLR) 9 activation and differential phosphorylation of interferon regulatory factor 3 and 7. The modulation of p75NTR on pDCs significantly influences disease progression of asthma in an ovalbumin-induced mouse model mediated by the TLR9 signaling pathway. p75NTR activation of pDCs from patients with asthma increased allergen-specific T cell proliferation and cytokine secretion in nerve growth factor concentration-dependent manner. Further, p75NTR activation of pDCs delayed the onset of autoimmune diabetes in RIP-CD80GP mice and aggravated graft-versus-host disease in a xenotransplantation model. Thus, p75NTR signaling on pDCs constitutes a new and critical mechanism connecting neurotrophin signaling and immune response regulation with great therapeutic potential for a variety of immune disorders.

Neurotrophin Receptor p75NTR Regulates Immune Function of Plasmacytoid Dendritic Cells

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Joanna Bandoła

2017-08-01

Full Text Available Plasmacytoid dendritic cells (pDCs regulate innate and adaptive immunity. Neurotrophins and their receptors control the function of neuronal tissue. In addition, they have been demonstrated to be part of the immune response but little is known about the effector immune cells involved. We report, for the first time, the expression and immune-regulatory function of the low affinity neurotrophin receptor p75 neurotrophin receptor (p75NTR by the antigen-presenting pDCs, mediated by toll-like receptor (TLR 9 activation and differential phosphorylation of interferon regulatory factor 3 and 7. The modulation of p75NTR on pDCs significantly influences disease progression of asthma in an ovalbumin-induced mouse model mediated by the TLR9 signaling pathway. p75NTR activation of pDCs from patients with asthma increased allergen-specific T cell proliferation and cytokine secretion in nerve growth factor concentration-dependent manner. Further, p75NTR activation of pDCs delayed the onset of autoimmune diabetes in RIP-CD80GP mice and aggravated graft-versus-host disease in a xenotransplantation model. Thus, p75NTR signaling on pDCs constitutes a new and critical mechanism connecting neurotrophin signaling and immune response regulation with great therapeutic potential for a variety of immune disorders.

HIV enteropathy and aging: gastrointestinal immunity, mucosal epithelial barrier, and microbial translocation.

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Wang, Hongyin; Kotler, Donald P

2014-07-01

Despite decreases in morbidity and mortality as a result of antiretroviral therapy, gastrointestinal dysfunction remains common in HIV infection. Treated patients are at risk for complications of 'premature' aging, such as cardiovascular disease, osteopenia, neurocognitive decline, malignancies, and frailty. This review summarizes recent observations in this field. Mucosal CD4 lymphocytes, especially Th17 cells, are depleted in acute HIV and simian immune deficiency virus (SIV) infections, although other cell types also are affected. Reconstitution during therapy often is incomplete, especially in mucosa. Mucosal barrier function is affected by both HIV infection and aging and includes paracellular transport via tight junctions and uptake through areas of apoptosis; other factors may affect systemic antigen exposure. The resultant microbial translocation is associated with systemic immune activation in HIV and SIV infections. There is evidence of immune activation and microbial translocation in the elderly. The immune phenotypes of immunosenescence in HIV infection and aging appear similar. There are several targets for intervention; blockage of residual mucosal virus replication, preventing antigen uptake, modulating the microbiome, improving T cell recovery, combining therapies aimed at mucosal integrity, augmenting mucosal immunity, and managing traditional risk factors for premature aging in the general population. Aging may interact with HIV enteropathy to enhance microbial translocation and immune activation.

Pilot projects and nation-wide immunization in India.

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Haxton, D

1984-01-01

These studies identify possibilities for expanding immunization coverage in India and show that there have been positive experiences in going to scale with immunizationation at the district level. Reasons for success are discussed. The promotion of social awareness and participation through all available channels is of central importance. Continuing attention should be directed to vaccine supply and distribution systems, program management and manpower training, especially at the community level. There are many opportunities for extending involvement in immunization efforts and broad-spectrum programs beyond the confines of the health system, and for flexibility in program organization. Planning must incorporate political commitment as well as the provision of adequate financial resources. India launched the Expanded Program on Immunization (EPI) in 1978. 6 diseases are currently on the official schedule for progressive nation-wide immunization: tuberculosis, poliomyelitis, whooping cough, diptheria, tetanus and typhoid. The experiences of 3 efforts in Dewas, in Bidar, (2 rural areas), and in Delhi (an urban area) are covered. Immunization coverage before the intensive efforts did not exceed 30%. Major elements of program organization were: nonhealth sector political and administrative involvement from the state; multisectoral planning committees at different levels; household surveys to identify children to be immunized; training sessions for each category of workers; and strengthening the cold chain. Factors in operational design and implementation include: vaccination posts in the community; selection of acceptable vaccination days; reminders the day before vaccination; collection of children; immunization cards as a device for informing about next round; counteraction of side-effects; follow-up of drop-outs; monitoring for corrective action involving all participants; and formal evaluation by local medical colleges. Intensive immunization in the 3 pilot sites

Immunity by equilibrium.

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Eberl, Gérard

2016-08-01

The classical model of immunity posits that the immune system reacts to pathogens and injury and restores homeostasis. Indeed, a century of research has uncovered the means and mechanisms by which the immune system recognizes danger and regulates its own activity. However, this classical model does not fully explain complex phenomena, such as tolerance, allergy, the increased prevalence of inflammatory pathologies in industrialized nations and immunity to multiple infections. In this Essay, I propose a model of immunity that is based on equilibrium, in which the healthy immune system is always active and in a state of dynamic equilibrium between antagonistic types of response. This equilibrium is regulated both by the internal milieu and by the microbial environment. As a result, alteration of the internal milieu or microbial environment leads to immune disequilibrium, which determines tolerance, protective immunity and inflammatory pathology.

Immune checkpoint inhibitors for metastatic bladder cancer.

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Massari, Francesco; Di Nunno, Vincenzo; Cubelli, Marta; Santoni, Matteo; Fiorentino, Michelangelo; Montironi, Rodolfo; Cheng, Liang; Lopez-Beltran, Anto; Battelli, Nicola; Ardizzoni, Andrea

2018-03-01

Chemotherapy has represented the standard therapy for unresectable or metastatic urothelial carcinoma for more than 20 years. The growing knowledge of the interaction between tumour and immune system has led to the advent of new classes of drugs, the immune-checkpoints inhibitors, which are intended to change the current scenario. To date, immunotherapy is able to improve the overall responses and survival. Moreover, thanks to its safety profile immune-checkpoint inhibitors could be proposed also to patients unfit for standard chemotherapy. No doubts that these agents have started a revolution expected for years, but despite this encouraging results it appears clear that not all subjects respond to these agents and requiring the development of reliable predictive response factors able to isolate patients who can more benefit from these treatments as well as new strategies aimed to improve immunotherapy clinical outcome. In this review we describe the active or ongoing clinical trials involving Programmed Death Ligand 1 (PD-L1), Programmed Death receptor 1 (PD-1) and Cytotoxic-T Lymphocyte Antigen 4 (CTLA 4) inhibitors in urothelial carcinoma focusing our attention on the developing new immune-agents and combination strategies with immune-checkpoint inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

OpenAIRE

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

2012-01-01

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

Cross-immunity among allogeneic tumors of rats immunized with solid tumors

International Nuclear Information System (INIS)

Ogasawara, Masamichi

1979-01-01

Several experiments were done for the study of cross-immunity among allogeneic rat tumors by immunization using gamma-irradiated or non-irradiated solid tumors. Each group of rats which were immunized with gamma-irradiation solid tumor inocula from ascites tumor cell line of tetra-ploid Hirosaki sarcoma, Usubuchi sarcoma or AH 130, showed an apparent resistance against the intraperitoneal challenge with Hirosaki sarcoma. A similar resistance was demonstrated in the case of the challenge with Usubuchi sarcoma into rats immunized with non-irradiated methylcholanthrene (MCA)-induced tumors. In using solid MCA tumors as immunogen and Hirosaki sarcoma as challenge tumor, it was also demonstrated in 2 out of 3 groups immunized with non-irradiated tumors. In the experiment of trying to induce cross-immunity between 2 MCA tumors by immunization with irradiated solid tumor only, the inhibitory effect on the growth was observed in the early stage in the treated groups as compared with the control one. From the above results, it may be considered that the immunization with irradiated solid tumors fromas cites cell lines and non-irradiated solid MCA tumors induced strong cross-immunity in general, but that the immunization with only irradiated solid MCA tumors induced weak cross-immunity commonly. (author)

Linear ubiquitination in immunity.

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Shimizu, Yutaka; Taraborrelli, Lucia; Walczak, Henning

2015-07-01

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

Microbial-immune cross-talk and regulation of the immune system.

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Cahenzli, Julia; Balmer, Maria L; McCoy, Kathy D

2013-01-01

We are all born germ-free. Following birth we enter into a lifelong relationship with microbes residing on our body's surfaces. The lower intestine is home to the highest microbial density in our body, which is also the highest microbial density known on Earth (up to 10(12) /g of luminal contents). With our indigenous microbial cells outnumbering our human cells by an order of magnitude our body is more microbial than human. Numerous immune adaptations confine these microbes within the mucosa, enabling most of us to live in peaceful homeostasis with our intestinal symbionts. Intestinal epithelial cells not only form a physical barrier between the bacteria-laden lumen and the rest of the body but also function as multi-tasking immune cells that sense the prevailing microbial (apical) and immune (basolateral) milieus, instruct the underlying immune cells, and adapt functionally. In the constant effort to ensure intestinal homeostasis, the immune system becomes educated to respond appropriately and in turn immune status can shape the microbial consortia. Here we review how the dynamic immune-microbial dialogue underlies maturation and regulation of the immune system and discuss recent findings on the impact of diet on both microbial ecology and immune function. © 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.