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  • Kidd, Brian  (6)
  • Maecker, Holden  (6)
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  • 1
    Online Resource
    Online Resource
    A Systemic Age Dependent Defect in Immune-cell Signaling Response is Associated with Longevity Biomarkers
    Elsevier BV ; 2010
    In:  Clinical Immunology Vol. 135 ( 2010-1), p. S20-
    Details
    In: Clinical Immunology, Elsevier BV, Vol. 135 ( 2010-1), p. S20-
    Type of Medium: Online Resource
    ISSN: 1521-6616
    URL: Article
    DOI: 10.1016/j.clim.2010.03.066
    RVK:
    XA 36852
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2010
    detail.hit.zdb_id: 1462862-4
    Location Call Number Limitation Availability
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    Online Resource
  • 2
    Online Resource
    Online Resource
    A Systemic age dependent defect in immune-cell signaling response induced by inflammation (138.2)
    The American Association of Immunologists ; 2010
    In:  The Journal of Immunology Vol. 184, No. 1_Supplement ( 2010-04-01), p. 138.2-138.2
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 184, No. 1_Supplement ( 2010-04-01), p. 138.2-138.2
    Abstract: Immune system function generally degrades with age and is associated with increased risk of infection and disease. Though differences between young and old have been noted in many immune system components, no system wide understanding of how these disparate observation act together exists to date, nor how they relate to genes found to associated with increased longevity, many of which are immune related. Here we characterize the immune system of 29 young and old individuals by concurrently measuring from peripheral blood, immune cell subset frequency, serum cytokines, gene expression and individual cellular responses to cytokine stimuli by pathway specific phospho-protein abundance. We identify age-dependent changes in STAT signaling baseline and in response to stimulation by a panel of 7 different cytokines, particularly prominent in CD8 and CD4 T cells, but also in monocytes and B-cells. The observed differences in cellular responses are not due to adaptation to higher level of cytokine stimuli but rather to an inert inability to mount a full response, many times augmented by a higher base line phosphorylation level in the elderly. We construct an immune network spanning multiple biological layers and identify co-occurring modules which link longevity associated genes with these cellular immune phenotypes. We quantify the contributions of these modules to the observed reduction in cellular response to stimuli in the elderly and suggest a common responsible mechanism.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.184.Supp.138.2
    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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    Online Resource
  • 3
    Online Resource
    Online Resource
    High-throughput multi-parameter analysis of human immune responses to the seasonal Influenza vaccine in the elderly and young subjects: defining metrics of immune health and immune senescence (138.4)
    The American Association of Immunologists ; 2010
    In:  The Journal of Immunology Vol. 184, No. 1_Supplement ( 2010-04-01), p. 138.4-138.4
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 184, No. 1_Supplement ( 2010-04-01), p. 138.4-138.4
    Abstract: Aging is a complex process in which the immune function is severely affected. Increased prevalence of infectious diseases and poor vaccine responses are characteristic in the elderly. Here we seek to define the immune response to the seasonal inactivated Influenza vaccine in young subjects and in an elderly population with the aim of finding signatures of immune health and immune senescence. Ninety-one subjects, age-ranges 20-30, 60-79 and 80-96, were drawn prior to the vaccine, 7 and 21 days after vaccination. PBMC were isolated to phenotype 18 immune cell subsets and for high-throughput analysis of signaling phosphoproteins in multiple cell-subsets, after various stimulations. Serum samples were used to determine cytokine levels and antibody titers to the vaccine strains and to non-circulating Influenza strains. Dramatic age-related changes in STAT signaling were observed in CD8 and CD4 T cells when stimulated with IL-6, IFN-α or IFN-γ. The level of PLCγ phosphorylation in B cells from older subjects was significantly lower than the observed in the younger group, independently of the reduced B cell frequency. Weak antibody response against the vaccine strains while high level of seroprotection against older non-circulating vaccines was seen in the elderly and strongly associated to the IL-6 or IFN-α pathways. A better comprehension of human immune aging is necessary for designing age-specific vaccines with higher efficacy.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.184.Supp.138.4
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2010
    detail.hit.zdb_id: 1475085-5
    Location Call Number Limitation Availability
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    Online Resource
  • 4
    Online Resource
    Online Resource
    The split-virus influenza vaccine activates Fcγ receptors instead of Toll-like receptors (VAC2P.930)
    The American Association of Immunologists ; 2014
    In:  The Journal of Immunology Vol. 192, No. 1_Supplement ( 2014-05-01), p. 72.8-72.8
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 192, No. 1_Supplement ( 2014-05-01), p. 72.8-72.8
    Abstract: Seasonal influenza vaccination is the most common medical procedure targeting the immune system and yet the extent to which influenza vaccination activates innate immunity in humans is not fully understood. Currently, the most prevalent formulations of the vaccine consist of degraded or “split” viral particles often prepared without any adjuvants. We sought to determine whether the unadjuvanted split influenza vaccine activates innate immune receptors—specifically Toll-like receptors. A mass-cytometry (CyTOF) based proteomic profiling platform was developed and used to compare signaling pathway activation and cytokine production between the split influenza vaccine and a prototypical TLR response in human whole-blood (ex vivo). This analysis revealed that the split vaccine rapidly and potently activates multiple immune cell types but yields a proteomic signature distinct from TLR activation. Importantly, vaccine induced activity was dependent upon the presence of human sera indicating that a serum factor was necessary for vaccine-dependent immune activation. We found this serum factor to be human antibodies specific for influenza proteins and therefore immediate immune activation by the split vaccine is immune-complex dependent. These studies demonstrate that influenza vaccine splitting inactivates any microbial adjuvants endogenous to influenza but potentially elicits a potent immune modulator by facilitating the rapid formation of immune complexes.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.192.Supp.72.8
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2014
    detail.hit.zdb_id: 1475085-5
    Location Call Number Limitation Availability
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  • 5
    Online Resource
    Online Resource
    Strong antibody responses to influenza vaccination are associated with cell survival/proliferation and pro-apoptotic immune traits (110.27)
    The American Association of Immunologists ; 2011
    In:  The Journal of Immunology Vol. 186, No. 1_Supplement ( 2011-04-01), p. 110.27-110.27
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 186, No. 1_Supplement ( 2011-04-01), p. 110.27-110.27
    Abstract: Vaccination is the most effective strategy to prevent and control infectious diseases through induction of antibodies that neutralize the pathogen. However, little is known on what immune traits underlie an effective antibody response. With the aim of finding correlates of vaccine response that predict the antibody titers against an influenza vaccine, we studied the antibody responses to the seasonal trivalent influenza vaccine in a young and older individuals, and assayed a comprehensive set of immune parameters that included whole blood gene expression, determination of serum cytokine levels, leukocyte subset frequencies and phosphorylation of signaling proteins upon stimulation of various peripheral blood cells. We have found that rise in antibody titers to influenza strains after vaccination is strongly associated with high pro-apoptotic and low cell survival/proliferation levels of diverse immune traits and genes that could be exploited to improve vaccine responses in those less protected.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.186.Supp.110.27
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2011
    detail.hit.zdb_id: 1475085-5
    Location Call Number Limitation Availability
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  • 6
    Online Resource
    Online Resource
    Decoupling age from cytomegalovirus-associated changes in the immune system (109.28)
    The American Association of Immunologists ; 2011
    In:  The Journal of Immunology Vol. 186, No. 1_Supplement ( 2011-04-01), p. 109.28-109.28
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 186, No. 1_Supplement ( 2011-04-01), p. 109.28-109.28
    Abstract: CMV infection has been associated with premature immunosenescence and shorter lifespan. To date, no systems-wide analysis for decoupling age from CMV associated changes have been conducted. To address the differences between an immune system in naïve versus CMV infected humans and to decouple the age-related from CMV-related changes, we studied a comprehensive set of assays comprising serum cytokines, cell subset frequencies, whole genome gene expression and various stimulations of immune cells in 30 young and 60 older, CMV seropositive or seronegative individuals. For each measurement we performed a multiple regression analysis on all samples by age, CMV serostatus and the interaction between both variables (age × cmv). We found dramatic differences in multiple measurements of the immune system by age - mostly affecting T cell signaling responses, inflammatory cytokines and many immune-related genes, by CMV - which seems to preferentially modulate the CD4 and B cell compartments at different levels - or when both factors are present with changes mostly restricted to B cell functions. We present, for the first time, a systems immunology view of CMV- and age-associated changes in the immune system.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.186.Supp.109.28
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2011
    detail.hit.zdb_id: 1475085-5
    Location Call Number Limitation Availability
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    Online Resource
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