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Scooped by
Gilbert C FAURE
May 3, 2018 8:08 AM
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Toronto-based BenchSci, a search engine for researchers to look for biological products, has raised a $10 million Series A from iNovia Capital.
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Scooped by
Gilbert C FAURE
May 2, 2018 12:04 PM
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During the resolution of inflammation, macrophages engulf apoptotic polymorphonuclear cells (PMN) and can accumulate large numbers of their corpses. Here we report that resolution-phase-macrophages acquire the neutrophil-derived glycoprotein lactoferrin (Lf) and fragments thereof in vivo and ex vivo. During the onset and resolving phases of inflammation in murine peritonitis and bovine mastitis Lf fragments of 15 and 17 kDa occurred in various body fluids, and the murine fragmentation, accumulation and release were mediated initially by neutrophils, and later by efferocytic macrophages. The 17 kDa fragment contained two bioactive tripeptides, FKD and FKE that promoted resolution phase macrophage conversion to a pro-resolving phenotype. This resulted in a reduction in peritoneal macrophage numbers and an increase in the CD11blow subset of these cells. Moreover, FKE, but not FKD, peptides enhanced efferocytosis of apoptotic PMN, reduced TNFalpha and IL-6 and increased IL-10 secretion by LPS-stimulated macrophages ex vivo. In addition, FKE promoted neutrophil-mediated resolution at high concentrations (100 microM) by enhancing the formation of cytokine-scavenging aggregated NETs (tophi) at low cellular density. Thus, PMN lactoferrin is processed, acquired, and "recycled" by neutrophils and macrophages during inflammation resolution to generate fragments and peptides with paramount pro-resolving activities.
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Suggested by
LIGHTING
April 30, 2018 8:23 AM
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“NETtling” the host: Breaking of tolerance in chronic inflammation and chronic infection
Sladjana Skopelja-Gardner, Jonatha
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Scooped by
Gilbert C FAURE
April 29, 2018 5:55 AM
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IUIS - International Union of Immunological Societies
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Scooped by
Gilbert C FAURE
April 27, 2018 8:48 AM
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For World Primary Immunodeficiency Week 2018, the BSI have collected a range of resources focusing on primary immundeficiencies.
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Suggested by
LIGHTING
April 27, 2018 1:52 AM
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Gordon et al. demonstrate that CX3CR1int peripheral memory T cells are a substantial
component of memory inflation induced by persistent CMVs and adenoviral vaccination.
They are characterized by sustained proliferation and an effector-memory phenotype
linked to these expanded CD8+ T cell memory responses. Core phenotypic features are
shared by humans and mice.
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Scooped by
Gilbert C FAURE
April 23, 2018 9:05 AM
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Tuberculosis remains one of the leading causes of mortality worldwide, and, despite its clinical significance, there are still significant gaps in our understanding of pathogenic and protective mechanisms triggered by Mycobacterium tuberculosis infection. Type I interferons (IFN) regulate a broad family of genes that either stimulate or inhibit immune function, having both host-protective and detrimental effects, and exhibit well-characterized antiviral activity. Transcriptional studies have uncovered a potential deleterious role for type I IFN in active tuberculosis. Since then, additional studies in human tuberculosis and experimental mouse models of M. tuberculosis infection support the concept that type I IFN promotes both bacterial expansion and disease pathogenesis. More recently, studies in a different setting have suggested a putative protective role for type I IFN. In this study, we discuss the mechanistic and contextual factors that determine the detrimental versus beneficial outcomes of type I IFN induction during M. tuberculosis infection, from human disease to experimental mouse models of tuberculosis.
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Scooped by
Gilbert C FAURE
April 22, 2018 12:02 PM
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The generation of memory B cells (MBCs) that have undergone immunoglobulin class switching from IgM, which dominates primary antibody responses, to other immunoglobulin isoforms is a hallmark of immune memory. Hence, humoral immunological memory is characterized by the presence of serum immunoglobulins of IgG subtypes known as the γ‐globulin fraction of blood plasma proteins. These antibodies reflect the antigen experience of B lymphocytes and their repeated triggering. In fact, efficient protection against a previously encountered pathogen is critically linked to the production of pathogen‐specific IgG molecules even in those cases where the primary immune response required cellular immunity, for example, T cell‐mediated clearance of intracellular pathogens such as viruses. Besides IgG, also IgA and IgE can provide humoral immunity depending on the microbe's nature and infection route. The molecular mechanisms underlying the preponderance of switched immunoglobulin isotypes during memory antibody responses are a matter of active and controversial debate. Here, we summarize the phenotypic characteristics of distinct MBC subpopulations and discuss the decisive roles of different B cell antigen receptor isotypes for the functional traits of class‐switched B cell populations.
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Scooped by
Gilbert C FAURE
April 22, 2018 12:00 PM
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Annu Rev Immunol. 2018 Apr 26;36:309-338. doi: 10.1146/annurev-immunol-042617-053245.
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Scooped by
Gilbert C FAURE
April 20, 2018 3:23 PM
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Memory T cells: where do they come from and how is their production controlled? Researchers from the Scripps Research Institute believe they have the answe
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Rescooped by
Gilbert C FAURE
from Immunology and Biotherapies
April 20, 2018 9:27 AM
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Natural killer (NK) cells perform immune surveillance for virally infected cells and tumor cells. The balance between the engagement of activating receptors, such as NKG2D, and inhibitory receptors on the NK cell surface determines whether the cells kill their targets. Through superresolution microscopy, Bálint et al . showed that NKG2D on the surface of unstimulated NK cells was organized into nanoclusters, which became differentially reorganized depending on whether the cells were exposed to MICA or ULBP2, two NKG2D ligands found on tumor cells. Stimulation with ULBP2, but not MICA, caused NKG2D to cluster with the receptor for the cytokine IL-15, which can also be presented on tumor cells, synergizing with NKG2D to enhance NK cell responses. These data suggest that NKG2D ligands have distinct outcomes on NK cell function, which may have relevance in the use of NK cells as an immunotherapy.
Via Krishan Maggon
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Suggested by
LIGHTING
April 18, 2018 11:37 AM
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Immunol Rev. 2018 May;283(1):7-20. doi: 10.1111/imr.12652. Review
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Scooped by
Gilbert C FAURE
April 17, 2018 2:07 PM
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Scooped by
Gilbert C FAURE
May 3, 2018 4:06 AM
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IUIS/FAIS Immuno KENYA 2018 Nairobi September 23-28 2018 How viruses hijack host immunity leading to Cancers
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Suggested by
LIGHTING
May 2, 2018 1:56 AM
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In non-pathogenic situations, the immune system interacts with the nervous system
and diet components to regulate complex physiological processes, including metabolic
homeostasis, thermogenesis, and tissue repair.
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Scooped by
Gilbert C FAURE
April 29, 2018 5:58 AM
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For International Day of Immunology 2018, the BSI has teamed up with the Francis Crick Institute and Nature Research to deliver a panel discussion hosted by top immunologists on the relationship between the immune system of the gut and the commensal bacteria it is home to. We have also collected a range of related resources focusing on gut immunology and how immunology has evolved over the 60 years of the BSI's existence.
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Scooped by
Gilbert C FAURE
April 29, 2018 5:54 AM
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IUIS - International Union of Immunological Societies
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Scooped by
Gilbert C FAURE
April 27, 2018 2:26 AM
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![Figure][1]
Adaptive immunity is initiated by T cell recognition of specific antigens presented by major histocompatibility complexes (MHCs). MHC multimer technology has been developed for the detection, isolation, and characterization of T cells in infection, autoimmunity, and cancer. Here, we present a simple, fast, flexible, and efficient method to generate many different MHC class I (MHC I) multimers in parallel using temperature-mediated peptide exchange. We designed conditional peptides for HLA-A*02:01 and H-2Kb that form stable peptide–MHC I complexes at low temperatures, but dissociate when exposed to a defined elevated temperature. The resulting conditional MHC I complexes, either alone or prepared as ready-to-use multimers, can swiftly be loaded with peptides of choice without additional handling and within a short time frame. We demonstrate the ease and flexibility of this approach by monitoring the antiviral immune constitution in an allogeneic stem cell transplant recipient and by analyzing CD8+ T cell responses to viral epitopes in mice infected with lymphocytic choriomeningitis virus or cytomegalovirus.
[1]: pending:yes
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Suggested by
LIGHTING
April 25, 2018 12:04 PM
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NK cells are cytotoxic lymphocytes important in defense against viral infection and cancer. NK cells mediate cytotoxicity predominantly through directed secretion of lytic granules, which are specialized lysosome-related organelles, containing effector molecules such as perforin and granzymes. Although many requirements for lytic granule transport to, and secretion at, the NK cell lytic synapse are known, the minimum number of degranulation events required by an NK cell to kill its target is unknown. We performed high-resolution four-dimensional confocal microscopy of human NK–target cell conjugates to quantify NK cell degranulation (using a degranulation indicator, LAMP-1–pHluorin) as well as target cell death. Despite containing almost 200 granules, we found that an individual NK cell needed only two to four degranulation events, on average, to mediate target cell death. Although NK cells released approximately one-tenth of their total lytic granule reserve upon a single target, they required just over one-hundredth of their total lytic granules to kill a target cell. Importantly, the kinetics of NK cell killing correlated to the size of and the amount of effector molecules contained within lytic granules, as well as the temporal, but not spatial, organization of degranulation events. Thus, our study answers a fundamental question as to how many degranulation events it takes for a human NK cell to kill its target.
This article is featured in In This Issue , p.[3025][1]
[1]: /lookup/volpage/200/3025
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Suggested by
LIGHTING
April 23, 2018 6:56 AM
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Researchers find that T-cell receptors act alone, rather than interact with one another, for effective immune signaling
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Scooped by
Gilbert C FAURE
April 22, 2018 12:01 PM
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Asthma is a chronic inflammatory disease affecting the airway, and it is characterized by a wheezing breathing sound, variable airflow obstruction and the presence of inflammatory cells in the submucosa of the bronchi.
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Scooped by
Gilbert C FAURE
April 22, 2018 2:27 AM
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Age-related macular degeneration (AMD) is a devastating neurodegenerative disease affecting millions worldwide. Complement activation, inflammation, and the loss of choroidal endothelial cells (CECs) have been established as key factors in both normal aging and AMD; however, the exact mechanisms for these events have yet to be fully uncovered. Herein, we provide evidence that the prototypic acute phase reactant, C-reactive protein (CRP), contributes to AMD pathogenesis. We discuss serum CRP levels as a risk factor for disease, immunolocalization of distinct forms of CRP in the at-risk and diseased retina, and direct effects of CRP on ocular tissue. Furthermore, we discuss the complement system as it relates to AMD pathophysiology, provide a model for the role of CRP in this disease, and outline current therapies being developed and tested to treat AMD patients.
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Scooped by
Gilbert C FAURE
April 20, 2018 9:29 AM
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Author summary Type I interferons (IFNs) play a predominant role in the immune response to infectious pathogens. The cellular targets of IFNs have been difficult to dissect because of the ubiquitous expression of the type I interferon receptor (IFNAR).
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Scooped by
Gilbert C FAURE
April 19, 2018 2:58 PM
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Ise et al. identify the plasma cell-prone LZ GC B cells whose generation relies on
the amount of CD40 signal. Higher expression of ICAM-1 and SLAM in those cells facilitates
more stable contacts with Tfh cells, suggesting that strength of Tfh-GC B cell interaction
critically regulates formation of plasma cell precursors.
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Suggested by
LIGHTING
April 18, 2018 11:37 AM
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Scoop.it!
to check, reagents or immunotherapies?