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  • The American Association of Immunologists  (5)
  • 1
    Online Resource
    Online Resource
    Double-Stranded RNA Induces an Antiviral Defense Status in Epidermal Keratinocytes through TLR3-, PKR-, and MDA5/RIG-I-Mediated Differential Signaling
    The American Association of Immunologists ; 2008
    In:  The Journal of Immunology Vol. 181, No. 4 ( 2008-08-15), p. 2694-2704
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 181, No. 4 ( 2008-08-15), p. 2694-2704
    Abstract: Emerging evidence suggests an important role for human epidermal keratinocytes in innate immune mechanisms against bacterial and viral skin infections. The proinflammatory effect of viral infections can be mimicked by double-stranded RNA (dsRNA). Herein, we demonstrate that keratinocytes express all known dsRNA sensing receptors at a constitutive and inducible level, and that they use several downstream signaling pathways leading to a broad pattern of gene expression, not only proinflammatory and immune response genes under the control of NF-κB, but also genes under transcriptional control of IRF3. As a consequence, dsRNA, a stimulus for TLR3, protein kinase R (PKR), and the RNA helicases retinoic acid-inducible gene I (RIG-I) and MDA5, induces a status of antiviral defense in keratinocytes. Using inhibitors for the various dsRNA signaling pathways and specific small interfering RNA for TLR3, RIG-I, and MDA5, we demonstrated that in human keratinocytes, TLR3 seems to be necessary for NF-κB but not for IRF3 activation, whereas RIG-I and MDA5 are crucial for IRF3 activation. PKR is essential for the dsRNA response in both signaling pathways and thus represents the central antiviral receptor for dsRNA stimulation. Moreover, human keratinocytes up-regulate TLR7, the receptor for single-stranded RNA, in response to stimulation with dsRNA, which renders keratinocytes functionally responsive to the TLR7 agonist gardiquimod, a member of the imidazoquinoline antiviral immune response modifier family. Thus, in addition to building a physical barrier against infectious pathogens, keratinocytes are specially equipped with a full antiviral defense program that enables them to efficiently target viral infections of the skin.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.181.4.2694
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2008
    detail.hit.zdb_id: 1475085-5
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  • 2
    Online Resource
    Online Resource
    Detection of auto-IgE in pediatric atopic eczema indicates autosensitization as an early immunological event. (177.12)
    The American Association of Immunologists ; 2012
    In:  The Journal of Immunology Vol. 188, No. 1_Supplement ( 2012-05-01), p. 177.12-177.12
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 188, No. 1_Supplement ( 2012-05-01), p. 177.12-177.12
    Abstract: IgE-mediated allergies (e.g. asthma, atopic eczema [AE]) affect about 25% of western populations. Autoreactive IgE was detected in AE-patients and suspected to aggravate and chronify the disease. It is unclear, if autosensitization is a complication due to chronic allergic inflammation in adults or whether it is already present in children. Aims of this study were to develop a high-throughput assay for serologic detection of auto-IgE and to analyze if auto-IgE is organ-specific. We established an immunoassay to screen autoreactivity against whole cell protein extracts from primary keratinocytes (pKc) from non-AE and AE-patients, intestinal- and airway epithelial cells. After defining optimal conditions for all protein-extracts, we established a 384 well plate based immunoassay. We compared IgE-reactivity of 106 AE-patients (10mo.-70y.) and healthy controls on protein-extracts of all four cell types. 25% of AE-pts. showed IgE-autoreactivity against pKc from non-AE patients, 29% against pKc of AE-pts. and 33% against FHs74 Int. cells. Interestingly, the highest reactivity was detected in children. pKc from non-AE and AE-pts. bound more auto-IgE than HaCaT cells. This study identified auto-IgE at a similar level as reported previously. The IgE-specificity did not show organ-specificity, but auto-IgE seems to be an early immunological feature of AE in children. Current studies in birth-cohorts address the kinetics of auto-IgE-levels in relation to age and disease activity.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.188.Supp.177.12
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2012
    detail.hit.zdb_id: 1475085-5
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  • 3
    Online Resource
    Online Resource
    Human CD56bright NK Cells: An Update
    The American Association of Immunologists ; 2016
    In:  The Journal of Immunology Vol. 196, No. 7 ( 2016-04-01), p. 2923-2931
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 196, No. 7 ( 2016-04-01), p. 2923-2931
    Abstract: Human NK cells can be subdivided into various subsets based on the relative expression of CD16 and CD56. In particular, CD56brightCD16−/dim NK cells are the focus of interest. They are considered efficient cytokine producers endowed with immunoregulatory properties, but they can also become cytotoxic upon appropriate activation. These cells were shown to play a role in different disease states, such as cancer, autoimmunity, neuroinflammation, and infection. Although their phenotype and functional properties are well known and have been extensively studied, their lineage relationship with other NK cell subsets is not fully defined, nor is their precise hematopoietic origin. In this article, we summarize recent studies about CD56bright NK cells in health and disease and briefly discuss the current controversies surrounding them.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.1502570
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2016
    detail.hit.zdb_id: 1475085-5
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  • 4
    Online Resource
    Online Resource
    Identification, Recombinant Expression, and Characterization of the 100 kDa High Molecular Weight Hymenoptera Venom Allergens Api m 5 and Ves v 3
    The American Association of Immunologists ; 2010
    In:  The Journal of Immunology Vol. 184, No. 9 ( 2010-05-01), p. 5403-5413
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 184, No. 9 ( 2010-05-01), p. 5403-5413
    Abstract: Insect stings can cause life-threatening IgE-mediated anaphylactic reactions in venom-allergic patients. Although several compounds have already been described as venom allergens, prominent allergen candidates especially in the higher m.w. range have still remained elusive. Tandem mass spectrometry-based sequencing assigned a candidate gene to the most prominent putative high m.w. allergen Api m 5 (allergen C) in honeybee (Apis mellifera) venom and also allowed identification of its homologue Ves v 3 in yellow jacket (Vespula vulgaris) venom. Both proteins exhibit a pronounced sequence identity to human dipeptidyl peptidase IV or CD26. Reactivity of a human IgE mAb verified the presence of these proteins in the venoms. Both proteins were produced in insect cells and characterized for their enzymatic activity as well as their allergenic potential using sera and basophils from insect venom-allergic patients. Both Api m 5 and Ves v 3 were recognized by specific IgE of the majority of patients even in the absence of cross-reactive carbohydrate determinants. Serologic IgE reactivity closely matched activation of human basophils by Api m 5 or Ves v 3, thus underlining their relevance in functional assays. With Api m 5 and Ves v 3, a new pair of homologous allergens becomes available for future clinical applications in diagnosis and therapy that may also contribute to the understanding of molecular mechanisms of insect venoms. Moreover, the patient IgE reactivity together with the cellular activation demonstrates for the first time the relevance of high m.w. allergens in the context of hymenoptera venom allergy.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.0803709
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2010
    detail.hit.zdb_id: 1475085-5
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  • 5
    Online Resource
    Online Resource
    Standard Peripheral Blood Mononuclear Cell Cryopreservation Selectively Decreases Detection of Nine Clinically Relevant T Cell Markers
    The American Association of Immunologists ; 2021
    In:  ImmunoHorizons Vol. 5, No. 8 ( 2021-08-01), p. 711-720
    Details
    In: ImmunoHorizons, The American Association of Immunologists, Vol. 5, No. 8 ( 2021-08-01), p. 711-720
    Abstract: Biobanking is an operational component of various epidemiological studies and clinical trials. Although peripheral blood is routinely acquired and stored in biobanks, the effects of specimen processing on cell composition and clinically relevant functional markers of T cells still require a systematic evaluation. In this study, we assessed 25 relevant T cell markers in human PBMCs and showed that the detection of nine membrane markers (e.g., PD-1, CTLA4, KLRG1, CD25, CD122, CD127, CCR7, and others reflecting exhaustion, senescence, and other functions) was reduced among at least one T cell subset following standard processing, although the frequency of CD4, CD8, and regulatory T cells was unaffected. Nevertheless, a 6-mo-long cryopreservation did not impair the percentages of cells expressing many other membrane and all the eight tested intracellular lineage or functional T cell markers. Our findings uncover that several clinically relevant markers are particularly affected by processing and the interpretation of those results in clinical trials and translational research should be done with caution.
    Type of Medium: Online Resource
    ISSN: 2573-7732
    URL: Article
    DOI: 10.4049/immunohorizons.2100049
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2021
    detail.hit.zdb_id: 2882729-6
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