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Trends in Immunology

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https://www.readbyqxmd.com/read/28549714/the-enigmatic-role-of-viruses-in-multiple-sclerosis-molecular-mimicry-or-disturbed-immune-surveillance
#1
REVIEW
Jens Geginat, Moira Paroni, Massimiliano Pagani, Daniela Galimberti, Raffaele De Francesco, Elio Scarpini, Sergio Abrignani
Multiple sclerosis (MS) is a T cell driven autoimmune disease of the central nervous system (CNS). Despite its association with Epstein-Barr Virus (EBV), how viral infections promote MS remains unclear. However, there is increasing evidence that the CNS is continuously surveyed by virus-specific T cells, which protect against reactivating neurotropic viruses. Here, we discuss how viral infections could lead to the breakdown of self-tolerance in genetically predisposed individuals, and how the reactivations of viruses in the CNS could induce the recruitment of both autoaggressive and virus-specific T cell subsets, causing relapses and progressive disability...
May 23, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28539189/the-individual-and-population-genetics-of-antibody-immunity
#2
REVIEW
Corey T Watson, Jacob Glanville, Wayne A Marasco
Antibodies (Abs) produced by immunoglobulin (IG) genes are the most diverse proteins expressed in humans. While part of this diversity is generated by recombination during B-cell development and mutations during affinity maturation, the germ-line IG loci are also diverse across human populations and ethnicities. Recently, proof-of-concept studies have demonstrated genotype-phenotype correlations between specific IG germ-line variants and the quality of Ab responses during vaccination and disease. However, the functional consequences of IG genetic variation in Ab function and immunological outcomes remain underexplored...
May 20, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28511816/mechanisms-of-immune-tolerance-in-leukemia-and-lymphoma
#3
REVIEW
Emily K Curran, James Godfrey, Justin Kline
The mechanisms through which immune responses are generated against solid cancers are well characterized and knowledge of the immune evasion pathways exploited by these malignancies has grown considerably. However, for hematological cancers, which develop and disseminate quite differently than solid tumors, the pathways that regulate immune activation or tolerance are less clear. Growing evidence suggests that, while numerous immune escape pathways are shared between hematological and solid malignancies, several unique pathways are exploited by leukemia and lymphoma...
May 13, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28511815/signature-of-the-sleeper-cell-a-biomarker-of-hiv-latency-revealed
#4
Satish K Pillai, Steven G Deeks
HIV establishes a reservoir in latently infected T cells, and this reservoir has long hampered curative approaches. A recent study by Descours et al. identifies CD32a as a marker of latently infected T cells, potentially opening the way to the development of strategies that directly target this critical HIV reservoir.
May 13, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28499492/mechanisms-and-dynamics-of-t-cell-mediated-cytotoxicity-in-vivo
#5
REVIEW
Stephan Halle, Olga Halle, Reinhold Förster
Cytotoxic T lymphocytes (CTLs) are critical in the elimination of infected or malignant cells and are emerging as a major therapeutic target. How CTLs recognize and kill harmful cells has been characterized in vitro but little is known about these processes in the living organism. Here we review recent insights into CTL-mediated killing with an emphasis on in vivo CTL biology. Specifically, we focus on the possible rate-limiting steps determining the efficiency of CTL-mediated killing. We also highlight the need for cell-based datasets that permit the quantification of CTL dynamics, including CTL location, migration, and killing rates...
May 9, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28462845/rheostatic-functions-of-mast-cells-in-the-control-of-innate-and-adaptive-immune-responses
#6
REVIEW
Barbara Frossi, Francesca Mion, Claudio Tripodo, Mario P Colombo, Carlo E Pucillo
Mast cells are evolutionarily ancient cells, endowed with a unique developmental, phenotypic, and functional plasticity. They are resident cells that participate in tissue homeostasis by constantly sampling the microenvironment. As a result of their large repertoire of receptors, they can respond to multiple stimuli and selectively release different types and amounts of mediator. Here, we present and discuss the recent mast cell literature, focusing on studies that demonstrate that mast cells are more than a switch that is turned 'off' when in the resting state and 'on' when in the degranulating state...
April 24, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28438491/immunomodulatory-functions-of-neuronal-guidance-proteins
#7
REVIEW
Valbona Mirakaj, Peter Rosenberger
Neuronal guidance proteins (NGPs) were originally identified for their role during the embryonic development of the nervous system. Recent years have seen the discovery of NGP functions during immune responses. In this context, NGPs were demonstrated to control leukocyte migration and the release of cytokines during conditions of acute inflammation, such as lung injury or sepsis. However, NGPs also display potent actions in the resolution of inflammation, chronic inflammatory conditions, the development of atherosclerosis, and during ischemia followed by reperfusion...
April 21, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28416449/complement-c3-targeted-therapy-replacing-long-held-assertions-with-evidence-based-discovery
#8
REVIEW
Dimitrios C Mastellos, Edimara S Reis, Daniel Ricklin, Richard J Smith, John D Lambris
Complement dysregulation underlies several inflammatory disorders, and terminal complement inhibition has thus far afforded significant clinical gains. Nonetheless, emerging pathologies, fueled by complement imbalance and therapy-skewing genetic variance, underscore the need for more comprehensive, disease-tailored interventions. Modulation at the level of C3, a multifaceted orchestrator of the complement cascade, opens up prospects for broader therapeutic efficacy by targeting multiple pathogenic pathways modulated by C3-triggered proinflammatory crosstalk...
April 14, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28416448/immunological-memory-of-group-2-innate-lymphoid-cells
#9
REVIEW
Itziar Martinez-Gonzalez, Laura Mathä, Catherine A Steer, Fumio Takei
Immunological memory has long been described as a property of the adaptive immune system that results in potent responses on exposure to an antigen encountered previously. While this definition appears to exclude cells that do not express antigen receptors, recent studies have shown that innate immune cells, including natural killer (NK) cells, macrophages, and, more recently, group 2 innate lymphoid cells (ILC2s) can record previous activations and respond more vigorously on reactivation. Here we review the similarities and differences between these forms of memory and the underlying mechanisms...
April 14, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28416447/evolutionary-origins-of-cgas-sting-signaling
#10
REVIEW
Shally R Margolis, Stephen C Wilson, Russell E Vance
Detection of foreign nucleic acids is an important strategy for innate immune recognition of pathogens. In vertebrates, pathogen-derived DNA is sensed in the cytosol by cGAS, which produces the cyclic dinucleotide (CDN) second messenger cGAMP to activate the signaling adaptor STING. While induction of antiviral type I interferons (IFNs) is the major outcome of STING activation in vertebrates, it has recently become clear that core components of the cGAS-STING pathway evolved more than 600 million years ago, predating the evolution of type I IFNs...
April 14, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28416446/patterns-receptors-and-signals-regulation-of-phagosome-maturation
#11
REVIEW
Anne-Marie Pauwels, Matthias Trost, Rudi Beyaert, Eik Hoffmann
Recognition of microbial pathogens and dead cells and their phagocytic uptake by specialized immune cells are essential to maintain host homeostasis. Phagosomes undergo fusion and fission events with endosomal and lysosomal compartments, a process called 'phagosome maturation', which leads to the degradation of the phagosomal content. However, many phagocytic cells also act as antigen-presenting cells and must balance degradation and peptide preservation. Emerging evidence indicates that receptor engagement by phagosomal cargo, as well as inflammatory mediators and cellular activation affect many aspects of phagosome maturation...
April 14, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28396078/macrophage-immunometabolism-where-are-we-going
#12
REVIEW
Jan Van den Bossche, Luke A O'Neill, Deepthi Menon
A growing number of findings highlight the crucial role of metabolic reprogramming in macrophage activation. Metabolic pathways are closely interconnected and recent literature demonstrates the need for glucose metabolism in anti-inflammatory as well as inflammatory macrophages. Moreover, fatty acid oxidation (FAO) not only supports anti-inflammatory responses as described formerly but also drives inflammasome activation in inflammatory macrophages. Hence, defining glycolysis as proinflammatory and FAO as anti-inflammatory may be an oversimplification...
April 7, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28385520/the-immunoregulatory-roles-of-antibody-glycosylation
#13
REVIEW
Madeleine F Jennewein, Galit Alter
Beyond their role in neutralization, antibodies mediate functions such as phagocytosis, cytotoxicity, and maintenance of immune homeostasis. Two modifications to the constant domain control antibody activity: theirreversible genomic selection of isotype/subclass and alterations in glycosylation. Because glycosylation alters the affinity of antibodies for Fc receptors, evidence suggests that glycosylation is a central mechanism for the immune system to tune a broad range of biological activities. While monoclonal therapeutics have exploited glycosylation to improve function, its in vivo control and whether it may be selectively harnessed to target pathogens and/or tumors isunknown...
April 3, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28283352/the-s-c-ensory-immune-system-theory
#14
REVIEW
Henrique Veiga-Fernandes, António A Freitas
Viewpoints on the immune system have evolved across different paradigms, including the clonal selection theory, the idiotypic network, and the danger and tolerance models. Herein, we propose that in multicellular organisms, where panoplies of cells from different germ layers interact and immune cells are constantly generated, the behavior of the immune system is defined by the rules governing cell survival, systems physiology and organismic homeostasis. Initially, these rules were imprinted at the single cell-protist level, but supervened modifications in the transition to multicellular organisms...
March 7, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28274696/expanding-the-b-cell-centric-view-of-systemic-lupus-erythematosus
#15
REVIEW
Peter A Morawski, Silvia Bolland
Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by a breakdown of self-tolerance in B cells and the production of antibodies against nuclear self-antigens. Increasing evidence supports the notion that additional cellular contributors beyond B cells are important for lupus pathogenesis. In this review we consider recent advances regarding both the pathogenic and the regulatory role of lymphocytes in SLE beyond the production of IgG autoantibodies. We also discuss various inflammatory effector cell types involved in cytokine production, removal of self-antigens, and responses to autoreactive IgE antibodies...
March 5, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28318877/liver-resident-nk-cells-the-human-factor
#16
Victoria Male
Mouse liver contains two natural killer (NK) cell populations, one of which recirculates while the other is tissue resident. Following this discovery, several groups have sought to identify liver-resident NK (lrNK) cells in humans. Here, I present an overview of recent advances in the field.
May 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28285814/thymic-determinants-of-%C3%AE-%C3%AE-t-cell-differentiation
#17
REVIEW
Miguel Muñoz-Ruiz, Nital Sumaria, Daniel J Pennington, Bruno Silva-Santos
γd T cells have emerged as major sources of the proinflammatory cytokines interleukin-17 (IL-17) and interferon-γ (IFNγ) in multiple models of infection, cancer and autoimmune disease. However, unlike their αβ T cell counterparts that require peripheral activation for effector cell differentiation, γδ T cells instead can be 'developmentally programmed' in the thymus to generate discrete γδ T cell effector subsets with distinctive molecular signatures. Nonetheless, recent studies have presented conflicting viewpoints on the signals involved in thymic γδ T cell development and differentiation, namely on the role of both T cell receptor (TCR)-dependent and TCR-independent factors...
May 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28262471/psgl-1-a-new-player-in-the-immune-checkpoint-landscape
#18
REVIEW
Roberto Tinoco, Dennis C Otero, Amy A Takahashi, Linda M Bradley
P-selectin glycoprotein ligand-1 (PSGL-1) has long been studied as an adhesion molecule involved in immune cell trafficking and is recognized as a regulator of many facets of immune responses by myeloid cells. PSGL-1 also regulates T cell migration during homeostasis and inflammatory settings. However, recent findings indicate that PSGL-1 can also negatively regulate T cell function. Because T cell differentiation is finely tuned by multiple positive and negative regulatory signals that appropriately scale the magnitude of the immune response, PSGL-1 has emerged as an important checkpoint during this process...
May 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28254169/il-17-signaling-the-yin-and-the-yang
#19
REVIEW
Nilesh Amatya, Abhishek V Garg, Sarah L Gaffen
Interleukin (IL)-17 is the founding member of a novel family of inflammatory cytokines. While the proinflammatory properties of IL-17 are key to its host-protective capacity, unrestrained IL-17 signaling is associated with immunopathology, autoimmune disease, and cancer progression. In this review we discuss both the activators and the inhibitors of IL-17 signal transduction, and also the physiological implications of these events. We highlight the surprisingly diverse means by which these regulators control expression of IL-17-dependent inflammatory genes, as well as the major target cells that respond to IL-17 signaling...
May 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28279591/hla-g-at-the-interface-of-maternal-fetal-tolerance
#20
REVIEW
Leonardo M R Ferreira, Torsten B Meissner, Tamara Tilburgs, Jack L Strominger
During pregnancy, semiallogeneic fetal extravillous trophoblasts (EVT) invade the uterine mucosa without being rejected by the maternal immune system. Several mechanisms were initially proposed by Peter Medawar half a century ago to explain this apparent violation of the laws of transplantation. Then, three decades ago, an unusual human leukocyte antigen (HLA) molecule was identified: HLA-G. Uniquely expressed in EVT, HLA-G has since become the center of the present understanding of fetus-induced immune tolerance...
April 2017: Trends in Immunology
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