Multilayer regulation of CD4 T cell subset differentiation in the era of single cell genomics.
Abstract CD4 T cells are major immune cell types that mediate effector responses appropriate for diverse incoming threats. These cells have been categorized into different subsets based on how they are induced, expression of specific master transcription factors, and the resulting effector cell phenotypes as defined by expression of signature cytokines. However, recent studies assessing the expression of gene modules in single CD4 T cells, rather than expression of one or a few signature genes, have provided a more complex picture in which the canonical model does not fit as cleanly as proposed. Here, we review th...
Source: Advances in Immunology - March 26, 2019 Category: Allergy & Immunology Authors: Sungnak W, Wang C, Kuchroo VK Tags: Adv Immunol Source Type: research

Signaling control of antibody isotype switching.
Abstract Class switch recombination (CSR) generates isotype-switched antibodies with distinct effector functions essential for mediating effective humoral immunity. CSR is catalyzed by activation-induced deaminase (AID) that initiates DNA lesions in the evolutionarily conserved switch (S) regions at the immunoglobulin heavy chain (Igh) locus. AID-initiated DNA lesions are subsequently converted into DNA double stranded breaks (DSBs) in the S regions of Igh locus, repaired by non-homologous end-joining to effect CSR in mammalian B lymphocytes. While molecular mechanisms of CSR are well characterized, it remains les...
Source: Advances in Immunology - March 26, 2019 Category: Allergy & Immunology Authors: Chen Z, Wang JH Tags: Adv Immunol Source Type: research

Transcription factories in Ig κ allelic choice and diversity.
Transcription factories in Igκ allelic choice and diversity. Adv Immunol. 2019;141:33-49 Authors: Karki S, Banerjee S, Mclean K, Dinner A, Clark MR Abstract The vertebrate immune system is tasked with the challenge of responding to any pathogen the organism might encounter, and retaining memory of that pathogen in case of future infection. Recognition and memory of pathogens are encoded within the adaptive immune system and production of T and B lymphocytes with diverse antigen receptor repertoires. In B lymphocytes, diversity is generated by sequential recombination between Variable (V), Divers...
Source: Advances in Immunology - March 26, 2019 Category: Allergy & Immunology Authors: Karki S, Banerjee S, Mclean K, Dinner A, Clark MR Tags: Adv Immunol Source Type: research

Cis- and trans-factors affecting AID targeting and mutagenic outcomes in antibody diversification.
Abstract Antigen receptor diversification is a hallmark of adaptive immunity which allows specificity of the receptor to particular antigen. B cell receptor (BCR) or its secreted form, antibody, is diversified through antigen-independent and antigen-dependent mechanisms. During B cell development in bone marrow, BCR is diversified via V(D)J recombination mediated by RAG endonuclease. Upon stimulation by antigen, B cell undergo somatic hypermutation (SHM) to allow affinity maturation and class switch recombination (CSR) to change the effector function of the antibody. Both SHM and CSR are initiated by activation-in...
Source: Advances in Immunology - March 26, 2019 Category: Allergy & Immunology Authors: Yeap LS, Meng FL Tags: Adv Immunol Source Type: research

New Insights Into the Biology of CD8 Regulatory T Cells.
Abstract Regulatory T cells are central mediators of immune regulation and play an essential role in the maintenance of immune homeostasis in the steady state and under pathophysiological conditions. Disruption of CD8 Treg-dependent recognition of Qa-1-restricted self-antigens can result in dysregulated immune responses, tissue damage, autoimmune disease and cancer. Recent progress in studies on regulatory T cells of the CD8 lineage has provided new biological insight into this specialized regulatory T cell subpopulation. Identification of the Helios transcription factor as an essential control element for the dif...
Source: Advances in Immunology - October 29, 2018 Category: Allergy & Immunology Authors: Nakagawa H, Wang L, Cantor H, Kim HJ Tags: Adv Immunol Source Type: research

Tumor Necrosis Factor Receptor Superfamily in T Cell Priming and Effector Function.
Abstract The tumor necrosis factor receptor superfamily (TNFRSF) and their ligands mediate lymphoid tissue development and homeostasis in addition to key aspects of innate and adaptive immune responses. T cells of the adaptive immune system express a number of TNFRSF members that are used to receive signals at different instructive stages and produce several tumor necrosis factor superfamily (TNFSF) members as effector molecules. There is also one example of a TNFRSF member serving as a ligand for negative regulatory checkpoint receptors. In most cases, the ligands in afferent and efferent phases are membrane prot...
Source: Advances in Immunology - October 29, 2018 Category: Allergy & Immunology Authors: Muller J, Baeyens A, Dustin ML Tags: Adv Immunol Source Type: research

The Fly Way of Antiviral Resistance and Disease Tolerance.
Abstract Like humans, insects face the threat of viral infection. Despite having repercussions on human health and disease, knowledge gaps exist for how insects cope with viral pathogens. Drosophila melanogaster serves as an ideal insect model due to its genetic tractability. When encountering a pathogen, two major approaches to fight disease are resistance strategies and tolerance strategies. Disease resistance strategies promote the health of the infected host by reducing pathogen load. Multiple disease resistance mechanisms have been identified in Drosophila: RNA interference, Jak/STAT signaling, Toll signaling...
Source: Advances in Immunology - October 29, 2018 Category: Allergy & Immunology Authors: Chow J, Kagan JC Tags: Adv Immunol Source Type: research

The Microglial Response to Neurodegenerative Disease.
Abstract Microglia are a subset of tissue macrophages that constitute the major immune cell type of the central nervous system. These cells have long been known to change their morphology and functions in response to various neurological insults. Recently, a plethora of unbiased transcriptomics studies have revealed that across a broad spectrum of neurodegeneration-like disease models, microglia adopt a similar activation signature and perform similar functions. Despite these commonalities in response, the role of microglia has been described as both positive and negative in different murine disease models. In hum...
Source: Advances in Immunology - September 28, 2018 Category: Allergy & Immunology Authors: Song WM, Colonna M Tags: Adv Immunol Source Type: research

The First B-Cell Tolerance Checkpoint in Mice and Humans: Control by AID.
Abstract Activation-induced cytidine deaminase (AID) expression in the germinal center response drives the immunoglobulin class-switch recombination and V(D)J hypermutation necessary for efficacious, high-affinity antibody responses. That AID is expressed in developing lymphocytes is less well known, but represents an evolutionarily conserved pattern of lymphocyte development that is represented in all vertebrate species. Here we review the role of early, developmentally regulated AID expression in mice and humans and its role in establishing the first B-cell tolerance checkpoint. This newly recognized component o...
Source: Advances in Immunology - September 28, 2018 Category: Allergy & Immunology Authors: Kuraoka M, Meffre E, Kelsoe G Tags: Adv Immunol Source Type: research

RAG Chromatin Scanning During V(D)J Recombination and Chromatin Loop Extrusion are Related Processes.
Abstract An effective adaptive immune system depends on the ability of developing B and T cells to generate diverse immunoglobulin (Ig) and T cell receptor repertoires, respectively. Such diversity is achieved through a programmed somatic recombination process whereby germline V, D, and J segments of antigen receptor loci are assembled to form the variable region V(D)J exons of Ig and TCRs. Studies of this process, termed V(D)J recombination, have provided key insights into our understanding of a variety of general gene regulatory and DNA repair processes over the last several decades. V(D)J recombination is initi...
Source: Advances in Immunology - September 28, 2018 Category: Allergy & Immunology Authors: Lin SG, Ba Z, Alt FW, Zhang Y Tags: Adv Immunol Source Type: research

Eosinophil Development, Disease Involvement, and Therapeutic Suppression.
Abstract Human eosinophils have characteristic morphologic features, including a bilobed nucleus and cytoplasmic granules filled with cytotoxic and immunoregulatory proteins that are packaged in a specific manner. Eosinophil production in the bone marrow is exquisitely regulated by timely expression of a repertoire of transcription factors that work together via collaborative and hierarchical interactions to direct eosinophil development. In addition, proper granule formation, which occurs in a spatially organized manner, is an intrinsic checkpoint that must be passed for proper eosinophil production to occur. In ...
Source: Advances in Immunology - May 9, 2018 Category: Allergy & Immunology Authors: Fulkerson PC, Rothenberg ME Tags: Adv Immunol Source Type: research

Molecular Aspects of Allergens and Allergy.
Abstract Immunoglobulin E (IgE)-associated allergy is the most common immune disorder. More than 30% of the population suffer from symptoms of allergy which are often severe, disabling, and life threatening such as asthma and anaphylaxis. Population-based birth cohort studies show that up to 60% of the world population exhibit IgE sensitization to allergens, of which most are protein antigens. Thirty years ago the first allergen-encoding cDNAs have been isolated. In the meantime, the structures of most of the allergens relevant for disease in humans have been solved. Here we provide an update regarding what has be...
Source: Advances in Immunology - May 9, 2018 Category: Allergy & Immunology Authors: Valenta R, Karaulov A, Niederberger V, Gattinger P, van Hage M, Flicker S, Linhart B, Campana R, Focke-Tejkl M, Curin M, Eckl-Dorna J, Lupinek C, Resch-Marat Y, Vrtala S, Mittermann I, Garib V, Khaitov M, Valent P, Pickl WF Tags: Adv Immunol Source Type: research

Unexpected Roles for Intracellular Complement in the Regulation of Th1 Responses.
Abstract The complement system is generally recognized as an evolutionarily ancient and critical part of innate immunity required for the removal of pathogens that have breached the protective host barriers. It was originally defined as a liver-derived serum surveillance system that induces the opsonization and killing of invading microbes and amplifies the general inflammatory reactions. However, studies spanning the last four decades have established complement also as a vital bridge between innate and adaptive immunity. Furthermore, recent work on complement, and in particular its impact on human T helper 1 (Th...
Source: Advances in Immunology - May 9, 2018 Category: Allergy & Immunology Authors: West EE, Afzali B, Kemper C Tags: Adv Immunol Source Type: research

Chemokines: Critical Regulators of Memory T Cell Development, Maintenance, and Function.
Abstract Memory T cells are central to orchestrating antigen-specific recall responses in vivo. Compared to naïve T cells, memory T cells respond more quickly to cognate peptide:MHC with a shorter lag time for entering the cell cycle and exerting effector functions. However, it is now well established that this enhanced responsiveness is not the only mechanism whereby memory T cells are better equipped than naïve T cells to rapidly and robustly induce inflammation. In contrast to naïve T cells, memory T cells are composed of distinct subsets with unique trafficking patterns and localizations. Tissue...
Source: Advances in Immunology - May 9, 2018 Category: Allergy & Immunology Authors: Rahimi RA, Luster AD Tags: Adv Immunol Source Type: research

Molecular Classification of Primary Immunodeficiencies of T Lymphocytes.
Abstract Proper regulation of the immune system is required for protection against pathogens and preventing autoimmune disorders. Inborn errors of the immune system due to inherited or de novo germline mutations can lead to the loss of protective immunity, aberrant immune homeostasis, and the development of autoimmune disease, or combinations of these. Forward genetic screens involving clinical material from patients with primary immunodeficiencies (PIDs) can vary in severity from life-threatening disease affecting multiple cell types and organs to relatively mild disease with susceptibility to a limited range of ...
Source: Advances in Immunology - May 9, 2018 Category: Allergy & Immunology Authors: Comrie WA, Lenardo MJ Tags: Adv Immunol Source Type: research

Single-Cell Resolution of T Cell Immune Responses.
Abstract Single antigen-specific B or T lymphocytes are the smallest functional units, into which an adaptive immune response can be dissected. Today, novel high-throughput technologies are providing researches with increasingly complex information on the diverse phenotypic signatures of individual lymphocytes. With a focus on T cells, we summarize here, how computational approaches are becoming increasingly important to identify the relevant developmental boundaries and connections between these high-dimensional lymphocyte states. We then describe how these insights may be further expanded by novel experimental a...
Source: Advances in Immunology - February 21, 2018 Category: Allergy & Immunology Authors: Buchholz VR, Flossdorf M Tags: Adv Immunol Source Type: research

The Unusual Genetics and Biochemistry of Bovine Immunoglobulins.
Abstract Antibodies are the key circulating molecules that have evolved to fight infection by the adaptive immune system of vertebrates. Typical antibodies of most species contain six complementarity-determining regions (CDRs), where the third CDR of the heavy chain (CDR H3) has the greatest diversity and often makes the most significant contact with antigen. Generally, the process of V(D)J recombination produces a vast repertoire of antibodies; multiple V, D, and J gene segments recombine with additional junctional diversity at the V-D and D-J joints, and additional combinatorial possibilities occur through heavy...
Source: Advances in Immunology - February 21, 2018 Category: Allergy & Immunology Authors: Stanfield RL, Haakenson J, Deiss TC, Criscitiello MF, Wilson IA, Smider VV Tags: Adv Immunol Source Type: research

The Fate Choice Between Effector and Memory T Cell Lineages: Asymmetry, Signal Integration, and Feedback to Create Bistability.
Abstract CD8+ T cells clear primary infections with intracellular pathogens and provide long-term immunity against reinfection. Two different types of CD8+ T cells are responsible for these functions: short-lived effector T cells and memory T cells. The cellular relationship between these two types of CD8+ T cells has been subject to much investigation. Both cell types can derive from a single naïve CD8+ T cell precursor. Their generation requires a fate choice early during a T cell response. As a result, two populations of T cells emerge. One of these consists of terminally differentiated short-lived effecto...
Source: Advances in Immunology - February 21, 2018 Category: Allergy & Immunology Authors: Backer RA, Hombrink P, Helbig C, Amsen D Tags: Adv Immunol Source Type: research

Caveolin-1: The Unnoticed Player in TCR and BCR Signaling.
Abstract T and B lymphocytes are key players of the adaptive immune system. They recognize pathogenic cues via the T cell antigen receptor (TCR) and the B cell antigen receptor (BCR) to get activated and execute their protective function. TCR and BCR signaling are initiated at the plasma membrane and subsequently propagated into the cell, ultimately leading to cell activation and a protective immune response. However, inappropriate activation of T and B cells can be detrimental to the host resulting in autoimmune disorders, immunodeficiencies, and cancer. The TCR and BCR are located at the plasma membrane, which c...
Source: Advances in Immunology - February 21, 2018 Category: Allergy & Immunology Authors: Fiala GJ, Minguet S Tags: Adv Immunol Source Type: research

β2-Adrenoceptor Function in Asthma.
β2-Adrenoceptor Function in Asthma. Adv Immunol. 2017;136:1-28 Authors: Amrani Y, Bradding P Abstract β2-adrenoceptor agonists, often used in combination with corticosteroids, have been extensively used for the treatment of asthma. However, concerns have been raised regarding their adverse effects and safety including poor asthma control, life-threatening exacerbations, exacerbations that often require hospitalization, and asthma-related deaths. The question as to whether these adverse effects relate to the loss of their bronchoprotective action remains an interesting possibility. In the cha...
Source: Advances in Immunology - September 29, 2017 Category: Allergy & Immunology Authors: Amrani Y, Bradding P Tags: Adv Immunol Source Type: research

Emerging Roles for MAS-Related G Protein-Coupled Receptor-X2 in Host Defense Peptide, Opioid, and Neuropeptide-Mediated Inflammatory Reactions.
Abstract Mast cells (MCs) are tissue-resident immune cells that contribute to host defense but are best known for their roles in allergic and inflammatory diseases. In humans, MCs are divided into two subtypes based on the protease content of their secretory granules. Thus, human lung MCs contain only tryptase and are known as MCT, whereas skin MCs contain both tryptase and chymase and are known as MCTC. Patients with severe asthma display elevated MCs in the lung, which undergo phenotypic change from MCT to MCTC. Although the human genome contains four Mas related G protein coupled receptor X (MRGPRX) genes, an i...
Source: Advances in Immunology - September 29, 2017 Category: Allergy & Immunology Authors: Ali H Tags: Adv Immunol Source Type: research

Adhesion GPCRs in Regulating Immune Responses and Inflammation.
Hamann J Abstract The adhesion family comprises one of the five major clades of G protein-coupled receptors (GPCRs). Unlike conventional GPCRs, adhesion GPCRs (aGPCRs) have extended ectodomains with various protein folds that facilitate protein-protein interactions and, hence, putative cellular adhesive functions. Juxtaposed to the seven-pass transmembrane domain is a GPCR autoproteolysis-inducing domain that enables autoproteolytic cleavage of the receptor, resulting in a bipartite structure of many aGPCRs. aGPCRs are widely distributed and play critical roles in many developmental processes; yet, the underlying...
Source: Advances in Immunology - September 29, 2017 Category: Allergy & Immunology Authors: Lin HH, Hsiao CC, Pabst C, Hébert J, Schöneberg T, Hamann J Tags: Adv Immunol Source Type: research

GPCR Signaling in C. elegans and Its Implications in Immune Response.
Abstract The ability to sense environmental cues is central to the survival of living organisms. G-protein-coupled receptors (GPCRs) are, by far, the most diverse class of sensory receptors and play an important role in surveillance. As Caenorhabditis elegans lives in soil and feeds on bacteria, it must have strategies to differentiate between nutritious vs pathogenic bacteria. In C. elegans, lacking professional immune cells, GPCRs play a very important role in defense responses, for survival against pathogens. Here, we review a rich body of research to show that C. elegans uses GPCRs in different tissues for imm...
Source: Advances in Immunology - September 29, 2017 Category: Allergy & Immunology Authors: Gupta A, Singh V Tags: Adv Immunol Source Type: research

G Protein-Coupled Receptor Kinases in the Inflammatory Response and Signaling.
Abstract G protein-coupled receptor kinases (GRKs) are serine/threonine kinases that regulate a large and diverse class of G protein-coupled receptors (GPCRs). Through GRK phosphorylation and β-arrestin recruitment, GPCRs are desensitized and their signal terminated. Recent work on these kinases has expanded their role from canonical GPCR regulation to include noncanonical regulation of non-GPCR and nonreceptor substrates through phosphorylation as well as via scaffolding functions. Owing to these and other regulatory roles, GRKs have been shown to play a critical role in the outcome of a variety of physiolog...
Source: Advances in Immunology - September 29, 2017 Category: Allergy & Immunology Authors: Steury MD, McCabe LR, Parameswaran N Tags: Adv Immunol Source Type: research

Canonical and Noncanonical Signaling Roles of β-Arrestins in Inflammation and Immunity.
Canonical and Noncanonical Signaling Roles of β-Arrestins in Inflammation and Immunity. Adv Immunol. 2017;136:279-313 Authors: Ahmadzai MM, Broadbent D, Occhiuto C, Yang C, Das R, Subramanian H Abstract β-Arrestins are a highly conserved family of cytosolic adaptor proteins that contribute to many immune functions by orchestrating the desensitization and internalization of cell-surface G protein-coupled receptors (GPCRs) via well-studied canonical interactions. In cells of the innate and adaptive immune system, β-arrestins also subserve a parallel but less understood role in which they ...
Source: Advances in Immunology - September 29, 2017 Category: Allergy & Immunology Authors: Ahmadzai MM, Broadbent D, Occhiuto C, Yang C, Das R, Subramanian H Tags: Adv Immunol Source Type: research

G Protein-Coupled Kinin Receptors and Immunity Against Pathogens.
Abstract For decades, immunologists have considered the complement system as a paradigm of a proteolytic cascade that, acting cooperatively with the immune system, enhances host defense against infectious organisms. In recent years, advances made in thrombosis research disclosed a functional link between activated neutrophils, monocytes, and platelet-driven thrombogenesis. Forging a physical barrier, the fibrin scaffolds generated by synergism between the extrinsic and intrinsic (contact) pathways of coagulation entrap microbes within microvessels, limiting the systemic spread of infection while enhancing the clea...
Source: Advances in Immunology - September 29, 2017 Category: Allergy & Immunology Authors: Scharfstein J, Ramos PIP, Barral-Netto M Tags: Adv Immunol Source Type: research

Emerging Roles of Regulators of G Protein Signaling (RGS) Proteins in the Immune System.
Abstract The regulators of G protein signaling (RGS) proteins are a large, evolutionarily conserved group of intracellular proteins expressed in every cell type and tissue throughout the body including the immune system. Through their signature GTPase-activating protein (GAP) activity on heterotrimeric G proteins and interactions with signaling complexes and membrane constituents (e.g., lipids), RGS proteins determine the intensity and duration of G protein-coupled receptor-induced responses. They may also have a function in generating intracellular signaling gradients necessary for the directional migration of le...
Source: Advances in Immunology - September 29, 2017 Category: Allergy & Immunology Authors: Druey KM Tags: Adv Immunol Source Type: research

Roles of NHERF Family of PDZ-Binding Proteins in Regulating GPCR Functions.
Abstract Multicellular organisms are equipped with an array of G-protein-coupled receptors (GPCRs) that mediate cell-cell signaling allowing them to adapt to environmental cues and ultimately survive. This is mechanistically possible through complex intracellular GPCR machinery that encompasses a vast network of proteins. Within this network, there is a group called scaffolding proteins that facilitate proper localization of signaling proteins for a quick and robust GPCR response. One protein family within this scaffolding group is the PSD-95/Dlg/ZO-1 (PDZ) family which is important for GPCR localization, internal...
Source: Advances in Immunology - September 29, 2017 Category: Allergy & Immunology Authors: Broadbent D, Ahmadzai MM, Kammala AK, Yang C, Occhiuto C, Das R, Subramanian H Tags: Adv Immunol Source Type: research

P2Y Receptors in Immune Response and Inflammation.
eberg T Abstract Metabotropic pyrimidine and purine nucleotide receptors (P2Y receptors) are expressed in virtually all cells with implications in very diverse biological functions, including the well-established platelet aggregation (P2Y12), but also immune regulation and inflammation. The classical P2Y receptors bind nucleotides and are encoded by eight genes with limited sequence homology, while phylogenetically related receptors (e.g., P2Y12-like) recognize lipids and peptides, but also nucleotide derivatives. Growing lines of evidence suggest an important function of P2Y receptors in immune cell differentiati...
Source: Advances in Immunology - September 29, 2017 Category: Allergy & Immunology Authors: Le Duc D, Schulz A, Lede V, Schulze A, Thor D, Brüser A, Schöneberg T Tags: Adv Immunol Source Type: research

Preface.
PMID: 28950953 [PubMed - in process] (Source: Advances in Immunology)
Source: Advances in Immunology - September 29, 2017 Category: Allergy & Immunology Authors: Shukla AK Tags: Adv Immunol Source Type: research

Chromosome 17q21 Genes ORMDL3 and GSDMB in Asthma and Immune Diseases.
Abstract Chromosome 17q21 contains a cluster of genes including ORMDL3 and GSDMB, which have been highly linked to asthma in genome-wide association studies. ORMDL3 is localized to the endoplasmic reticulum and regulates downstream pathways including sphingolipids, metalloproteases, remodeling genes, and chemokines. ORMDL3 inhibits serine palmitoyl-CoA transferase, the rate-limiting enzyme for sphingolipid biosynthesis. In addition, ORMDL3 activates the ATF6α branch of the unfolded protein response which regulates SERCA2b and IL-6, pathways of potential importance to asthma. The SNP-linking chromosome 17q21 ...
Source: Advances in Immunology - August 24, 2017 Category: Allergy & Immunology Authors: Das S, Miller M, Broide DH Tags: Adv Immunol Source Type: research

Chemokine-Driven CD4(+) T Cell Homing: New Concepts and Recent Advances.
Abstract CD4(+) T cells are critical regulators of the adaptive immune system and have diverse roles in regulating responses to the broad array of microbes encountered. Appropriate execution of their effector function requires precise and coordinated migration of these cells to specific lymphoid niches and peripheral sites. This migration is largely controlled by dynamic expression of chemokine receptors and the discrete functions of distinct subsets of CD4(+) T cells can often be determined from their expression of specific chemokine receptors. In this chapter, we discuss recent advances in the subset-specific ho...
Source: Advances in Immunology - August 24, 2017 Category: Allergy & Immunology Authors: Gregor CE, Foeng J, Comerford I, McColl SR Tags: Adv Immunol Source Type: research

Complement System in Neural Synapse Elimination in Development and Disease.
Abstract Recent discoveries implicate the classical complement cascade in normal brain development and in disease. Complement proteins C1q, C3, and C4 participate in synapse elimination, tagging inappropriate synaptic connections between neurons for removal by phagocytic microglia that exist in a special, highly phagocytic state during the synaptic pruning period. Several neurodevelopmental disorders, such as schizophrenia and autism, are thought to be caused by an imbalance in synaptic pruning, and recent studies suggest that dysregulation of complement could promote this synaptic pruning imbalance. Moreover, in ...
Source: Advances in Immunology - August 24, 2017 Category: Allergy & Immunology Authors: Presumey J, Bialas AR, Carroll MC Tags: Adv Immunol Source Type: research

A Mechanistic Understanding of Pyroptosis: The Fiery Death Triggered by Invasive Infection.
Abstract Immune cells and skin and mucosal epithelial cells recognize invasive microbes and other signs of danger to sound alarms that recruit responder cells and initiate an immediate "innate" immune response. An especially powerful alarm is triggered by cytosolic sensors of invasive infection that assemble into multimolecular complexes, called inflammasomes, that activate the inflammatory caspases, leading to maturation and secretion of proinflammatory cytokines and pyroptosis, an inflammatory death of the infected cell. Work in the past year has defined the molecular basis of pyroptosis. Activated inf...
Source: Advances in Immunology - August 24, 2017 Category: Allergy & Immunology Authors: Liu X, Lieberman J Tags: Adv Immunol Source Type: research

γδ T Cells and B Cells.
γδ T Cells and B Cells. Adv Immunol. 2017;134:1-45 Authors: Born WK, Huang Y, Reinhardt RL, Huang H, Sun D, O'Brien RL Abstract γδ T cells constitute the third arm of a tripartite adaptive immune system in jawed vertebrates, besides αβ T cells and B cells. Like the other two lymphocyte-types, they express diverse antigen receptors, capable of specific ligand recognition. Functionally, γδ T cells represent a system of differentiated subsets, sometimes engaged in cross-regulation, which ultimately determines their effect on other components of the immune sy...
Source: Advances in Immunology - April 19, 2017 Category: Allergy & Immunology Authors: Born WK, Huang Y, Reinhardt RL, Huang H, Sun D, O'Brien RL Tags: Adv Immunol Source Type: research

Regulation of Innate and Adaptive Immunity by TGF β.
Regulation of Innate and Adaptive Immunity by TGFβ. Adv Immunol. 2017;134:137-233 Authors: Kelly A, Houston SA, Sherwood E, Casulli J, Travis MA Abstract Immune regulation by cytokines is crucial in maintaining immune homeostasis, promoting responses to infection, resolving inflammation, and promoting immunological memory. Additionally, cytokine responses drive pathology in immune-mediated disease. A crucial cytokine in the regulation of all aspects of an immune response is transforming growth factor beta (TGFβ). Although best known as a crucial regulator of T cell responses, TGFβ plays...
Source: Advances in Immunology - April 19, 2017 Category: Allergy & Immunology Authors: Kelly A, Houston SA, Sherwood E, Casulli J, Travis MA Tags: Adv Immunol Source Type: research

Humanized Immunoglobulin Mice: Models for HIV Vaccine Testing and Studying the Broadly Neutralizing Antibody Problem.
Abstract A vaccine that can effectively prevent HIV-1 transmission remains paramount to ending the HIV pandemic, but to do so, will likely need to induce broadly neutralizing antibody (bnAb) responses. A major technical hurdle toward achieving this goal has been a shortage of animal models with the ability to systematically pinpoint roadblocks to bnAb induction and to rank vaccine strategies based on their ability to stimulate bnAb development. Over the past 6 years, immunoglobulin (Ig) knock-in (KI) technology has been leveraged to express bnAbs in mice, an approach that has enabled elucidation of various B-cell ...
Source: Advances in Immunology - April 19, 2017 Category: Allergy & Immunology Authors: Verkoczy L Tags: Adv Immunol Source Type: research

A Chemoattractant-Guided Walk Through Lymphopoiesis: From Hematopoietic Stem Cells to Mature B Lymphocytes.
Abstract B lymphocytes develop from hematopoietic stem cells (HSCs) in specialized bone marrow niches composed of rare mesenchymal lineage stem/progenitor cells (MSPCs) and sinusoidal endothelial cells. These niches are defined by function and location: MSPCs are mostly perisinusoidal cells that together with a small subset of sinusoidal endothelial cells express stem cell factor, interleukin-7 (IL-7), IL-15, and the highest amounts of CXCL12 in bone marrow. Though rare, MSPCs are morphologically heterogeneous, highly reticular, and form a vast cellular network in the bone marrow parenchyma capable of interacting ...
Source: Advances in Immunology - April 19, 2017 Category: Allergy & Immunology Authors: Lim VY, Zehentmeier S, Fistonich C, Pereira JP Tags: Adv Immunol Source Type: research

Tissue-Specific Diversity and Functions of Conventional Dendritic Cells.
ml BU Abstract Dendritic cells (DCs) are versatile controllers of immunity, which sense infection or tissue damage and, accordingly, initiate innate and adaptive effector responses. In recent years, it has become evident that DCs exist as an independent hematopoietic lineage comprising several developmentally distinct and functionally specialized subsets that are strategically located in all organs to defend the organism against invading pathogens. Here, we review the diversity of DC subtypes found across tissues and discuss our current understanding of the tissue-specific functions of these cell types. PMID:...
Source: Advances in Immunology - April 19, 2017 Category: Allergy & Immunology Authors: Pakalniškytė D, Schraml BU Tags: Adv Immunol Source Type: research

Macrophages and Mitochondria: A Critical Interplay Between Metabolism, Signaling, and the Functional Activity.
Abstract Macrophages are phagocytic cells that participate in a broad range of cellular functions and they are key regulators of innate immune responses and inflammation. Mitochondria are highly dynamic endosymbiotic organelles that play key roles in cellular metabolism and apoptosis. Mounting evidence suggests that mitochondria are involved in the interplay between metabolism and innate immune responses. The ability of these organelles to alter the metabolic profile of a cell, thereby allowing an appropriate response to each situation, is crucial for the correct establishment of immune responses. Furthermore, mit...
Source: Advances in Immunology - February 23, 2017 Category: Allergy & Immunology Authors: Tur J, Vico T, Lloberas J, Zorzano A, Celada A Tags: Adv Immunol Source Type: research

Nucleic Acid Immunity.
Abstract Organisms throughout biology need to maintain the integrity of their genome. From bacteria to vertebrates, life has established sophisticated mechanisms to detect and eliminate foreign genetic material or to restrict its function and replication. Tremendous progress has been made in the understanding of these mechanisms which keep foreign or unwanted nucleic acids from viruses or phages in check. Mechanisms reach from restriction-modification systems and CRISPR/Cas in bacteria and archaea to RNA interference and immune sensing of nucleic acids, altogether integral parts of a system which is now appreciate...
Source: Advances in Immunology - February 23, 2017 Category: Allergy & Immunology Authors: Hartmann G Tags: Adv Immunol Source Type: research

About Training and Memory: NK-Cell Adaptation to Viral Infections.
Abstract Viral infections continuously challenge and shape our immune system. Due to their fine antigen recognition ability, adaptive lymphocytes protect against pathogen reencounter by generating specific immunological memory. Innate cells such as macrophages also adapt to pathogen challenge and mount resistance to reinfection, a phenomenon termed trained immunity. As part of the innate immunity, natural killer (NK) cells can display rapid effector functions and play a crucial role in the control of viral infections, especially by the β-herpesvirus cytomegalovirus (CMV). CMV activates the NK-cell pool by ind...
Source: Advances in Immunology - February 23, 2017 Category: Allergy & Immunology Authors: Hammer Q, Romagnani C Tags: Adv Immunol Source Type: research

Molecular Mechanisms of Somatic Hypermutation and Class Switch Recombination.
Abstract In order to promote an efficient humoral immune response, germinal center B cells modify both the antigen recognition and effector domains by programmed genetic alterations of their antibody genes. To do so, B cells use the enzyme activation-induced deaminase (AID), which transforms deoxycytidine into deoxyuridine at the immunoglobulin genes, triggering mutagenic DNA repair. Data accumulated during the past decade have significantly advanced our understanding of how AID activity is regulated and preferentially targeted to the immunoglobulin genes. There is also a better understanding of the ways by which ...
Source: Advances in Immunology - February 23, 2017 Category: Allergy & Immunology Authors: Methot SP, Di Noia JM Tags: Adv Immunol Source Type: research

Emerging Major Histocompatibility Complex Class I-Related Functions of NLRC5.
Abstract Recent evidence demonstrates a key role for the nucleotide-binding oligomerization domain-like receptor (NLR) family member NLRC5 (NLR family, CARD domain containing protein 5) in the transcriptional regulation of major histocompatibility complex (MHC) class I and related genes. Detailed information on NLRC5 target genes in various cell types and conditions is emerging. Thanks to its analogy to CIITA (class II major MHC transactivator), a NLR family member known for over 20 years to be the master regulator of MHC class II gene transcription, also the molecular mechanisms underlying NLRC5 function are bein...
Source: Advances in Immunology - February 23, 2017 Category: Allergy & Immunology Authors: Chelbi ST, Dang AT, Guarda G Tags: Adv Immunol Source Type: research

Context- and Tissue-Specific Regulation of Immunity and Tolerance by Regulatory T Cells.
Abstract The immune system has evolved to defend the organism against an almost infinite number of pathogens in a locally confined and antigen-specific manner while at the same time preserving tolerance to harmless antigens and self. Regulatory T (Treg) cells essentially contribute to an immunoregulatory network preventing excessive immune responses and immunopathology. There is emerging evidence that Treg cells not only operate in secondary lymphoid tissue but also regulate immune responses directly at the site of inflammation. Hence, the classification of Treg cells might need to be further extended by Treg cell...
Source: Advances in Immunology - October 24, 2016 Category: Allergy & Immunology Authors: Ulges A, Schmitt E, Becker C, Bopp T Tags: Adv Immunol Source Type: research

Pleiotropic Roles of Type 1 Interferons in Antiviral Immune Responses.
Abstract Since Isaac's and Lindenmann's seminal experiments over 50 years ago demonstrating a soluble factor generated from heat killed virus-stimulated chicken embryos could inhibit live influenza virus replication, the term interferon has been synonymous with inhibition of virus replication. While the antiviral properties of type 1 interferon (IFN-I) are undeniable, recent studies have reported expanding and somewhat unexpected roles of IFN-I signaling during both acute and persistent viral infections. IFN-I signaling can promote morbidity and mortality through induction of aberrant inflammatory responses and re...
Source: Advances in Immunology - October 24, 2016 Category: Allergy & Immunology Authors: Teijaro JR Tags: Adv Immunol Source Type: research

Endogenous Retroelements and the Host Innate Immune Sensors.
Abstract The ability to distinguish between self and nonself is the fundamental basis of the immune system in all organisms. The conceptual distinction between self and nonself, however, breaks down when it comes to endogenous retroviruses and other retroelements. While some retroelements retain the virus-like features including the capacity to replicate and reinvade the host genome, most have become inactive through mutations or host epigenetic silencing. And yet, accumulating evidence suggests that endogenous retroelements, both active and inactive, play important roles not only in pathogenesis of immune disorde...
Source: Advances in Immunology - October 24, 2016 Category: Allergy & Immunology Authors: Mu X, Ahmad S, Hur S Tags: Adv Immunol Source Type: research

B-Lymphopoiesis in Fetal Liver, Guided by Chemokines.
Abstract Early in embryonic development of mice, from day 12.5 after conception, myeloid-lymphoid bipotent progenitors, expressing receptors both for IL7 and CSF-1, migrate from embryonic blood into developing fetal liver. These progenitors also express multiple chemokine receptors, i.e., CCR7, CXCR3, CXCR4, and CXCR5, all on one cell. Their migration through LYVE-1+ vascular endothelium is guided by CCR7, recognizing the chemokine CCL19, and by CXCR3, recognizing CXCL10/11, chemokines which are both produced by the endothelium. Once inside fetal liver, the progenitors are attracted by the chemokine CXCL12 to ALCA...
Source: Advances in Immunology - October 24, 2016 Category: Allergy & Immunology Authors: Kajikhina K, Tsuneto M, Melchers F Tags: Adv Immunol Source Type: research

The Roles of the Secreted Phospholipase A2 Gene Family in Immunology.
Abstract Within the phospholipase A2 (PLA2) family that hydrolyzes phospholipids to yield fatty acids and lysophospholipids, secreted PLA2 (sPLA2) enzymes comprise the largest group containing 11 isoforms in mammals. Individual sPLA2s exhibit unique tissue or cellular distributions and enzymatic properties, suggesting their distinct biological roles. Although PLA2 enzymes, particularly cytosolic PLA2 (cPLA2α), have long been implicated in inflammation by driving arachidonic acid metabolism, the precise biological roles of sPLA2s have remained a mystery over the last few decades. Recent studies employing mice...
Source: Advances in Immunology - October 24, 2016 Category: Allergy & Immunology Authors: Murakami M, Yamamoto K, Miki Y, Murase R, Sato H, Taketomi Y Tags: Adv Immunol Source Type: research

Malondialdehyde Epitopes as Targets of Immunity and the Implications for Atherosclerosis.
Abstract Accumulating evidence suggests that oxidation-specific epitopes (OSEs) constitute a novel class of damage-associated molecular patterns (DAMPs) generated during high oxidative stress but also in the physiological process of apoptosis. To deal with the potentially harmful consequences of such epitopes, the immune system has developed several mechanisms to protect from OSEs and to orchestrate their clearance, including IgM natural antibodies and both cellular- and membrane-bound receptors. Here, we focus on malondialdehyde (MDA) epitopes as prominent examples of OSEs that trigger both innate and adaptive im...
Source: Advances in Immunology - May 30, 2016 Category: Allergy & Immunology Authors: Papac-Milicevic N, Busch CJ, Binder CJ Tags: Adv Immunol Source Type: research