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Annual Review of Immunology

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https://www.readbyqxmd.com/read/29677479/rig-i-and-other-rna-sensors-in-antiviral-immunity
#1
Kwan T Chow, Michael Gale, Yueh-Ming Loo
Pattern recognition receptors (PRRs) survey intra- and extracellular spaces for pathogen-associated molecular patterns (PAMPs) within microbial products of infection. Recognition and binding to cognate PAMP ligand by specific PRRs initiates signaling cascades that culminate in a coordinated intracellular innate immune response designed to control infection. In particular, our immune system has evolved specialized PRRs to discriminate viral nucleic acid from host. These are critical sensors of viral RNA to trigger innate immunity in the vertebrate host...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29677478/unfinished-business-evolution-of-the-mhc-and-the-adaptive-immune-system-of-jawed-vertebrates
#2
Jim Kaufman
The major histocompatibility complex (MHC) is a large genetic region with many genes, including the highly polymorphic classical class I and II genes that play crucial roles in adaptive as well as innate immune responses. The organization of the MHC varies enormously among jawed vertebrates, but class I and II genes have not been found in other animals. How did the MHC arise, and are there underlying principles that can help us to understand the evolution of the MHC? This review considers what it means to be an MHC and the potential importance of genome-wide duplication, gene linkage, and gene coevolution for the emergence and evolution of an adaptive immune system...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29677477/systems-immunology-learning-the-rules-of-the-immune-system
#3
Alexandra-Chloé Villani, Siranush Sarkizova, Nir Hacohen
Given the many cell types and molecular components of the human immune system, along with vast variations across individuals, how should we go about developing causal and predictive explanations of immunity? A central strategy in human studies is to leverage natural variation to find relationships among variables, including DNA variants, epigenetic states, immune phenotypes, clinical descriptors, and others. Here, we focus on how natural variation is used to find patterns, infer principles, and develop predictive models for two areas: (a) immune cell activation-how single-cell profiling boosts our ability to discover immune cell types and states-and (b) antigen presentation and recognition-how models can be generated to predict presentation of antigens on MHC molecules and their detection by T cell receptors...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29677476/cd4-helper-and-cd8-cytotoxic-t-cell-differentiation
#4
Ichiro Taniuchi
A fundamental question in developmental immunology is how bipotential thymocyte precursors generate both CD4+ helper and CD8+ cytotoxic T cell lineages. The MHC specificity of αβ T cell receptors (TCRs) on precursors is closely correlated with cell fate-determining processes, prompting studies to characterize how variations in TCR signaling are linked with genetic programs establishing lineage-specific gene expression signatures, such as exclusive CD4 or CD8 expression. The key transcription factors ThPOK and Runx3 have been identified as mediating development of helper and cytotoxic T cell lineages, respectively...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29677475/molecular-and-functional-neuroscience-in-immunity
#5
Valentin A Pavlov, Sangeeta S Chavan, Kevin J Tracey
The nervous system regulates immunity and inflammation. The molecular detection of pathogen fragments, cytokines, and other immune molecules by sensory neurons generates immunoregulatory responses through efferent autonomic neuron signaling. The functional organization of this neural control is based on principles of reflex regulation. Reflexes involving the vagus nerve and other nerves have been therapeutically explored in models of inflammatory and autoimmune conditions, and recently in clinical settings...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29677474/unraveling-the-complex-interplay-between-t-cell-metabolism-and-function
#6
Ramon I Klein Geltink, Ryan L Kyle, Erika L Pearce
Metabolism drives function, on both an organismal and a cellular level. In T cell biology, metabolic remodeling is intrinsically linked to cellular development, activation, function, differentiation, and survival. After naive T cells are activated, increased demands for metabolic currency in the form of ATP, as well as biomass for cell growth, proliferation, and the production of effector molecules, are met by rewiring cellular metabolism. Consequently, pharmacological strategies are being developed to perturb or enhance selective metabolic processes that are skewed in immune-related pathologies...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29677473/signaling-and-function-of-interleukin-2-in-t-lymphocytes
#7
Sarah H Ross, Doreen A Cantrell
The discovery of interleukin-2 (IL-2) changed the molecular understanding of how the immune system is controlled. IL-2 is a pleiotropic cytokine, and dissecting the signaling pathways that allow IL-2 to control the differentiation and homeostasis of both pro- and anti-inflammatory T cells is fundamental to determining the molecular details of immune regulation. The IL-2 receptor couples to JAK tyrosine kinases and activates the STAT5 transcription factors. However, IL-2 does much more than control transcriptional programs; it is a key regulator of T cell metabolic programs...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29677472/translating-immunology-into-therapeutic-concepts-for-inflammatory-bowel-disease
#8
Holm H Uhlig, Fiona Powrie
Inflammatory bowel disease (IBD) defines a spectrum of complex disorders. Understanding how environmental risk factors, alterations of the intestinal microbiota, and polygenetic and epigenetic susceptibility impact on immune pathways is key for developing targeted therapies. Mechanistic understanding of polygenic IBD is complemented by Mendelian disorders that present with IBD, pharmacological interventions that cause colitis, autoimmunity, and multiple animal models. Collectively, this multifactorial pathogenesis supports a concept of immune checkpoints that control microbial-host interactions in the gut by modulating innate and adaptive immunity, as well as epithelial and mesenchymal cell responses...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29677471/the-way-we-walked-with-immunology
#9
Kimishige Ishizaka
It has been a little more than 50 years since we discovered IgE, a key molecule for the allergic response and a target for treating allergies and severe asthma. Here, I trace my career, from the kindling of my interest in immunochemistry to groundbreaking discoveries in the biology and chemistry of immunoglobulins. I describe my service to the broader community of immunologists and my role in shaping departments and research institutes. My course starts in Japan and includes Southern California, Baltimore, and Denver...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29677470/complement-and-the-regulation-of-t-cell-responses
#10
Erin E West, Martin Kolev, Claudia Kemper
The complement system is an evolutionarily ancient key component of innate immunity required for the detection and removal of invading pathogens. It was discovered more than 100 years ago and was originally defined as a liver-derived, blood-circulating sentinel system that classically mediates the opsonization and lytic killing of dangerous microbes and the initiation of the general inflammatory reaction. More recently, complement has also emerged as a critical player in adaptive immunity via its ability to instruct both B and T cell responses...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29677469/multidomain-control-over-tec-kinase-activation-state-tunes-the-t-cell-response
#11
Amy H Andreotti, Raji E Joseph, James M Conley, Janet Iwasa, Leslie J Berg
Signaling through the T cell antigen receptor (TCR) activates a series of tyrosine kinases. Directly associated with the TCR, the SRC family kinase LCK and the SYK family kinase ZAP-70 are essential for all downstream responses to TCR stimulation. In contrast, the TEC family kinase ITK is not an obligate component of the TCR cascade. Instead, ITK functions as a tuning dial, to translate variations in TCR signal strength into differential programs of gene expression. Recent insights into TEC kinase structure have provided a view into the molecular mechanisms that generate different states of kinase activation...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29490165/the-immune-response-to-mycobacterium-tuberculosis-in-hiv-1-coinfected-persons
#12
Hanif Esmail, Catherine Riou, Elsa du Bruyn, Rachel Pei-Jen Lai, Yolande X R Harley, Graeme Meintjes, Katalin A Wilkinson, Robert J Wilkinson
Globally, about 36.7 million people were living with HIV infection at the end of 2015. The most frequent infection co-occurring with HIV-1 is Mycobacterium tuberculosis-374,000 deaths per annum are attributable to HIV-tuberculosis, 75% of those occurring in Africa. HIV-1 infection increases the risk of tuberculosis by a factor of up to 26 and alters its clinical presentation, complicates diagnosis and treatment, and worsens outcome. Although HIV-1-induced depletion of CD4+ T cells underlies all these effects, more widespread immune deficits also contribute to susceptibility and pathogenesis...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29490164/regulation-of-the-cell-biology-of-antigen-cross-presentation
#13
J Magarian Blander
Antigen cross-presentation is an adaptation of the cellular process of loading MHC-I molecules with endogenous peptides during their biosynthesis within the endoplasmic reticulum. Cross-presented peptides derive from internalized proteins, microbial pathogens, and transformed or dying cells. The physical separation of internalized cargo from the endoplasmic reticulum, where the machinery for assembling peptide-MHC-I complexes resides, poses a challenge. To solve this problem, deliberate rewiring of organelle communication within cells is necessary to prepare for cross-presentation, and different endocytic receptors and vesicular traffic patterns customize the emergent cross-presentation compartment to the nature of the peptide source...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29490163/exploiting-nanobodies-singular-traits
#14
Jessica R Ingram, Florian I Schmidt, Hidde L Ploegh
The unique class of heavy chain-only antibodies, present in Camelidae, can be shrunk to just the variable region of the heavy chain to yield VHHs, also called nanobodies. About one-tenth the size of their full-size counterparts, nanobodies can serve in applications similar to those for conventional antibodies, but they come with a number of signature advantages that find increasing application in biology. They not only function as crystallization chaperones but also can be expressed inside cells as such, or fused to other proteins to perturb the function of their targets, for example, by enforcing their localization or degradation...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29490162/rebooting-human-immunology
#15
Mark M Davis, Petter Brodin
Recent progress in both conceptual and technological approaches to human immunology have rejuvenated a field that has long been in the shadow of the inbred mouse model. This is a healthy development both for the clinical relevance of immunology and for the fact that it is a way to gain access to the wealth of phenomenology in the many human diseases that involve the immune system. This is where we are likely to discover new immunological mechanisms and principals, especially those involving genetic heterogeneity or environmental influences that are difficult to model effectively in inbred mice...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29400999/the-formation-and-function-of-granulomas
#16
Antonio J Pagán, Lalita Ramakrishnan
Granulomas are organized aggregates of macrophages, often with characteristic morphological changes, and other immune cells. These evolutionarily ancient structures form in response to persistent particulate stimuli-infectious or noninfectious-that individual macrophages cannot eradicate. Granulomas evolved as protective responses to destroy or sequester particles but are frequently pathological in the context of foreign bodies, infections, and inflammatory diseases. We summarize recent findings that suggest that the granulomatous response unfolds in a stepwise program characterized by a series of macrophage activations and transformations that in turn recruit additional cells and produce structural changes...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29400998/apoptosis-and-clearance-of-apoptotic-cells
#17
Shigekazu Nagata
The human body generates 10-100 billion cells every day, and the same number of cells die to maintain homeostasis in our body. Cells infected by bacteria or viruses also die. The cell death that occurs under physiological conditions mainly proceeds by apoptosis, which is a noninflammatory, or silent, process, while pathogen infection induces necroptosis or pyroptosis, which activates the immune system and causes inflammation. Dead cells generated by apoptosis are quickly engulfed by macrophages for degradation...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29400985/iga-function-in-relation-to-the-intestinal-microbiota
#18
Andrew J Macpherson, Bahtiyar Yilmaz, Julien P Limenitakis, Stephanie C Ganal-Vonarburg
IgA is the dominant immunoglobulin isotype produced in mammals, largely secreted across the intestinal mucosal surface. Although induction of IgA has been a hallmark feature of microbiota colonization following colonization in germ-free animals, until recently appreciation of the function of IgA in host-microbial mutualism has depended mainly on indirect evidence of alterations in microbiota composition or penetration of microbes in the absence of somatic mutations in IgA (or compensatory IgM). Highly parallel sequencing techniques that enable high-resolution analysis of either microbial consortia or IgA sequence diversity are now giving us new perspectives on selective targeting of microbial taxa and the trajectory of IgA diversification according to induction mechanisms, between different individuals and over time...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29400984/antigen-presentation-by-extracellular-vesicles-from-professional-antigen-presenting-cells
#19
Marthe F S Lindenbergh, Willem Stoorvogel
The initiation and maintenance of adaptive immunity require multifaceted modes of communication between different types of immune cells, including direct intercellular contact, secreted soluble signaling molecules, and extracellular vesicles (EVs). EVs can be formed as microvesicles directly pinched off from the plasma membrane or as exosomes secreted by multivesicular endosomes. Membrane receptors guide EVs to specific target cells, allowing directional transfer of specific and complex signaling cues. EVs are released by most, if not all, immune cells...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29394121/genetics-of-natural-killer-cells-in-human-health-disease-and-survival
#20
Peter Parham, Lisbeth A Guethlein
Natural killer (NK) cells have vital functions in human immunity and reproduction. In the innate and adaptive immune responses to infection, particularly by viruses, NK cells respond by secreting inflammatory cytokines and killing infected cells. In reproduction, NK cells are critical for genesis of the placenta, the organ that controls the supply of oxygen and nutrients to the growing fetus. Controlling NK cell functions are interactions of HLA class I with inhibitory NK cell receptors. First evolved was the conserved interaction of HLA-E with CD94:NKG2A; later established were diverse interactions of HLA-A, -B, and -C with killer cell immunoglobulin-like receptors...
April 26, 2018: Annual Review of Immunology
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