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Annual Review of Immunology

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https://www.readbyqxmd.com/read/29237129/zap-70-in-signaling-biology-and-disease
#1
Byron B Au-Yeung, Neel H Shah, Lin Shen, Arthur Weiss
T cells possess an array of functional capabilities important for host defense against pathogens and tumors. T cell effector functions require the T cell antigen receptor (TCR). The TCR has no intrinsic enzymatic activity, and thus signal transduction from the receptor relies on additional signaling molecules. One such molecule is the cytoplasmic tyrosine kinase ZAP-70, which associates with the TCR complex and is required for initiating the canonical biochemical signal pathways downstream of the TCR. In this article, we describe recent structure-based insights into the regulation and substrate specificity of ZAP-70, and then we review novel methods for determining the role of ZAP-70 catalytic activity-dependent and -independent signals in developing and mature T cells...
December 13, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/29237128/host-control-of-fungal-infections-lessons-from-basic-studies-and-human-cohorts
#2
Michail S Lionakis, Stuart M Levitz
In the last few decades, the AIDS pandemic and the significant advances in the medical management of individuals with neoplastic and inflammatory conditions have resulted in a dramatic increase in the population of immunosuppressed patients with opportunistic, life-threatening fungal infections. The parallel development of clinically relevant mouse models of fungal disease and the discovery and characterization of several inborn errors of immune-related genes that underlie inherited human susceptibility to opportunistic mycoses have significantly expanded our understanding of the innate and adaptive immune mechanisms that protect against ubiquitous fungal exposures...
December 13, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/29144838/human-t-cell-leukemia-virus-type-1-persistence-and-pathogenesis
#3
Charles R M Bangham
Human T cell leukemia virus type 1 (HTLV-1), also known as human T lymphotropic virus type 1, was the first exogenous human retrovirus discovered. Unlike the distantly related lentivirus HIV-1, HTLV-1 causes disease in only 5-10% of infected people, depending on their ethnic origin. But whereas HIV-1 infection and the consequent diseases can be efficiently contained in most cases by antiretroviral drug treatment, there is no satisfactory treatment for the malignant or inflammatory diseases caused by HTLV-1...
November 16, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/29144837/evolution-of-alternative-adaptive-immune-systems-in-vertebrates
#4
Thomas Boehm, Masayuki Hirano, Stephen J Holland, Sabyasachi Das, Michael Schorpp, Max D Cooper
Adaptive immunity in jawless fishes is based on antigen recognition by three types of variable lymphocyte receptors (VLRs) composed of variable leucinerich repeats, which are differentially expressed by two T-like lymphocyte lineages and one B-like lymphocyte lineage. The T-like cells express either VLRAs or VLRCs of yet undefined antigen specificity, whereas the VLRB antibodies secreted by B-like cells bind proteinaceous and carbohydrate antigens. The incomplete VLR germline genes are assembled into functional units by a gene conversion-like mechanism that employs flanking variable leucine-rich repeat sequences as templates in association with lineage-specific expression of cytidine deaminases...
November 16, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/29144836/autophagy-and-inflammation
#5
Yu Matsuzawa-Ishimoto, Seungmin Hwang, Ken Cadwell
The cellular degradative pathway of autophagy has a fundamental role in immunity. Here, we review the function of autophagy and autophagy proteins in inflammation. We discuss how the autophagy machinery controls the burden of infectious agents while simultaneously limiting inflammatory pathologies, which often involves processes that are distinct from conventional autophagy. Among the newly emerging processes we describe are LC3-associated phagocytosis and targeting by autophagy proteins, both of which require many of the same proteins that mediate conventional autophagy...
November 16, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28446063/synthetic-immunology-hacking-immune-cells-to-expand-their-therapeutic-capabilities
#6
Kole T Roybal, Wendell A Lim
The ability of immune cells to survey tissues and sense pathologic insults and deviations makes them a unique platform for interfacing with the body and disease. With the rapid advancement of synthetic biology, we can now engineer and equip immune cells with new sensors and controllable therapeutic response programs to sense and treat diseases that our natural immune system cannot normally handle. Here we review the current state of engineered immune cell therapeutics and their unique capabilities compared to small molecules and biologics...
April 26, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28446062/metabolite-sensing-g-protein-coupled-receptors-facilitators-of-diet-related-immune-regulation
#7
Jian K Tan, Craig McKenzie, Eliana MariƱo, Laurence Macia, Charles R Mackay
Nutrition and the gut microbiome regulate many systems, including the immune, metabolic, and nervous systems. We propose that the host responds to deficiency (or sufficiency) of dietary and bacterial metabolites in a dynamic way, to optimize responses and survival. A family of G protein-coupled receptors (GPCRs) termed the metabolite-sensing GPCRs bind to various metabolites and transmit signals that are important for proper immune and metabolic functions. Members of this family include GPR43, GPR41, GPR109A, GPR120, GPR40, GPR84, GPR35, and GPR91...
April 26, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28446061/signaling-by-antibodies-recent-progress
#8
Stylianos Bournazos, Taia T Wang, Rony Dahan, Jad Maamary, Jeffrey V Ravetch
IgG antibodies mediate a diversity of immune functions by coupling of antigen specificity through the Fab domain to signal transduction via Fc-Fc receptor interactions. Indeed, balanced IgG signaling through type I and type II Fc receptors is required for the control of proinflammatory, anti-inflammatory, and immunomodulatory processes. In this review, we discuss the mechanisms that govern IgG-Fc receptor interactions, highlighting the diversity of Fc receptor-mediated effector functions that regulate immunity and inflammation as well as determine susceptibility to infection and autoimmunity and responsiveness to antibody-based therapeutics and vaccines...
April 26, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28226229/a-perspective-on-the-role-of-computational-models-in-immunology
#9
Arup K Chakraborty
This is an exciting time for immunology because the future promises to be replete with exciting new discoveries that can be translated to improve health and treat disease in novel ways. Immunologists are attempting to answer increasingly complex questions concerning phenomena that range from the genetic, molecular, and cellular scales to that of organs, whole animals or humans, and populations of humans and pathogens. An important goal is to understand how the many different components involved interact with each other within and across these scales for immune responses to emerge, and how aberrant regulation of these processes causes disease...
April 26, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28226228/antigen-presenting-cells-in-the-skin
#10
Sakeen W Kashem, Muzlifah Haniffa, Daniel H Kaplan
Professional antigen-presenting cells (APCs) in the skin include dendritic cells, monocytes, and macrophages. They are highly dynamic, with the capacity to enter skin from the peripheral circulation, patrol within tissue, and migrate through lymphatics to draining lymph nodes. Skin APCs are endowed with antigen-sensing, -processing, and -presenting machinery and play key roles in initiating, modulating, and resolving cutaneous inflammation. Skin APCs are a highly heterogeneous population with functionally specialized subsets that are developmentally imprinted and modulated by local tissue microenvironmental and inflammatory cues...
April 26, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28226227/protective-and-harmful-immunity-to-rsv-infection
#11
Peter J M Openshaw, Chris Chiu, Fiona J Culley, Cecilia Johansson
Respiratory syncytial virus (RSV) is an exceptional mucosal pathogen. It specializes in infection of the ciliated respiratory epithelium, causing disease of variable severity with little or no direct systemic effects. It infects virtually all children by the age of three years and then repeatedly infects throughout life; this it does despite relatively slight variations in antigenicity, apparently by inducing selective immunological amnesia. Inappropriate or dysregulated responses to RSV can be pathogenic, causing disease-enhancing inflammation that contributes to short- and long-term effects...
April 26, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28226226/microglia-function-in-the-central-nervous-system-during-health-and-neurodegeneration
#12
Marco Colonna, Oleg Butovsky
Microglia are resident cells of the brain that regulate brain development, maintenance of neuronal networks, and injury repair. Microglia serve as brain macrophages but are distinct from other tissue macrophages owing to their unique homeostatic phenotype and tight regulation by the central nervous system (CNS) microenvironment. They are responsible for the elimination of microbes, dead cells, redundant synapses, protein aggregates, and other particulate and soluble antigens that may endanger the CNS. Furthermore, as the primary source of proinflammatory cytokines, microglia are pivotal mediators of neuroinflammation and can induce or modulate a broad spectrum of cellular responses...
April 26, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28226225/thymic-epithelial-cells
#13
Jakub Abramson, Graham Anderson
Intrathymic T cell development is a complex process that depends upon continuous guidance from thymus stromal cell microenvironments. The thymic epithelium within the thymic stroma comprises highly specialized cells with a high degree of anatomic, phenotypic, and functional heterogeneity. These properties are collectively required to bias thymocyte development toward production of self-tolerant and functionally competent T cells. The importance of thymic epithelial cells (TECs) is evidenced by clear links between their dysfunction and multiple diseases where autoimmunity and immunodeficiency are major components...
April 26, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28182501/disorders-of-the-jak-stat-pathway-in-t-cell-lymphoma-pathogenesis-implications-for-immunotherapy
#14
Thomas A Waldmann, Jing Chen
Common gamma receptor-dependent cytokines and their JAK/STAT pathways play pivotal roles in T cell immunity. Abnormal activation of this system was pervasive in diverse T cell malignancies assessed by pSTAT3/pSTAT5 phosphorylation. Activating mutations were described in some but not all cases. JAK1 and STAT3 were required for proliferation and survival of these T cell lines whether or not JAKs or STATs were mutated. Activating JAK and STAT mutations were not sufficient to initiate leukemic cell proliferation but rather only augmented signals from upstream in the cytokine pathway...
April 26, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28142324/memory-b-cells-of-mice-and-humans
#15
Florian Weisel, Mark Shlomchik
We comprehensively review memory B cells (MBCs), covering the definition of MBCs and their identities and subsets, how MBCs are generated, where they are localized, how they are maintained, and how they are reactivated. Whereas naive B cells adopt multiple fates upon stimulation, MBCs are more restricted in their responses. Evolving work reveals that the MBC compartment in mice and humans consists of distinct subpopulations with differing effector functions. We discuss the various approaches to define subsets and subset-specific roles...
April 26, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28142323/intracellular-nucleic-acid-detection-in-autoimmunity
#16
John T Crowl, Elizabeth E Gray, Kathleen Pestal, Hannah E Volkman, Daniel B Stetson
Protective immune responses to viral infection are initiated by innate immune sensors that survey extracellular and intracellular space for foreign nucleic acids. The existence of these sensors raises fundamental questions about self/nonself discrimination because of the abundance of self-DNA and self-RNA that occupy these same compartments. Recent advances have revealed that enzymes that metabolize or modify endogenous nucleic acids are essential for preventing inappropriate activation of the innate antiviral response...
April 26, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28142322/microbes-and-cancer
#17
Amiran Dzutsev, Jonathan H Badger, Ernesto Perez-Chanona, Soumen Roy, Rosalba Salcedo, Carolyne K Smith, Giorgio Trinchieri
Commensal microorganisms (the microbiota) live on all the surface barriers of our body and are particularly abundant and diverse in the distal gut. The microbiota and its larger host represent a metaorganism in which the cross talk between microbes and host cells is necessary for health, survival, and regulation of physiological functions locally, at the barrier level, and systemically. The ancestral molecular and cellular mechanisms stemming from the earliest interactions between prokaryotes and eukaryotes have evolved to mediate microbe-dependent host physiology and tissue homeostasis, including innate and adaptive resistance to infections and tissue repair...
April 26, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28142321/understanding-human-autoimmunity-and-autoinflammation-through-transcriptomics
#18
Romain Banchereau, Alma-Martina Cepika, Jacques Banchereau, Virginia Pascual
Transcriptomics, the high-throughput characterization of RNAs, has been instrumental in defining pathogenic signatures in human autoimmunity and autoinflammation. It enabled the identification of new therapeutic targets in IFN-, IL-1- and IL-17-mediated diseases. Applied to immunomonitoring, transcriptomics is starting to unravel diagnostic and prognostic signatures that stratify patients, track molecular changes associated with disease activity, define personalized treatment strategies, and generally inform clinical practice...
April 26, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28125358/immunobiology-of-long-noncoding-rnas
#19
Maninjay K Atianand, Daniel R Caffrey, Katherine A Fitzgerald
The discovery of long noncoding RNAs (lncRNA) has provided a new perspective on gene regulation in diverse biological contexts. lncRNAs are remarkably versatile molecules that interact with RNA, DNA, or proteins to promote or restrain the expression of protein-coding genes. Activation of immune cells is associated with dynamic changes in expression of genes, the products of which combat infectious microorganisms, initiate repair, and resolve inflammatory responses in cells and tissues. Recent evidence indicates that lncRNAs play important roles in directing the development of diverse immune cells and controlling the dynamic transcriptional programs that are a hallmark of immune cell activation...
April 26, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28125357/mucosal-ecological-network-of-epithelium-and-immune-cells-for-gut-homeostasis-and-tissue-healing
#20
Yosuke Kurashima, Hiroshi Kiyono
The intestinal epithelial barrier includes columnar epithelial, Paneth, goblet, enteroendocrine, and tuft cells as well as other cell populations, all of which contribute properties essential for gastrointestinal homeostasis. The intestinal mucosa is covered by mucin, which contains antimicrobial peptides and secretory IgA and prevents luminal bacteria, fungi, and viruses from stimulating intestinal immune responses. Conversely, the transport of luminal microorganisms-mediated by M, dendritic, and goblet cells-into intestinal tissues facilitates the harmonization of active and quiescent mucosal immune responses...
April 26, 2017: Annual Review of Immunology
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