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Advances in Immunology

Gina J Fiala, Susana Minguet
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...
2018: Advances in Immunology
Ronald A Backer, Pleun Hombrink, Christina Helbig, Derk Amsen
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...
2018: Advances in Immunology
Robyn L Stanfield, Jeremy Haakenson, Thaddeus C Deiss, Michael F Criscitiello, Ian A Wilson, Vaughn V Smider
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- and light-chain pairing...
2018: Advances in Immunology
Veit R Buchholz, Michael Flossdorf
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...
2018: Advances in Immunology
Arun K Shukla
No abstract text is available yet for this article.
2017: Advances in Immunology
Diana Le Duc, Angela Schulz, Vera Lede, Annelie Schulze, Doreen Thor, Antje Brüser, Torsten Schöneberg
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 differentiation and maturation, migration, and cell apoptosis...
2017: Advances in Immunology
David Broadbent, Mohammad M Ahmadzai, Ananth K Kammala, Canchai Yang, Christopher Occhiuto, Rupali Das, Hariharan Subramanian
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, internalization, recycling, and downstream signaling...
2017: Advances in Immunology
Kirk M Druey
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 leukocytes to inflamed tissues containing local accumulations of chemoattractants...
2017: Advances in Immunology
Julio Scharfstein, Pablo I P Ramos, Manoel Barral-Netto
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 clearance of pathogens by activated leukocytes...
2017: Advances in Immunology
Mohammad M Ahmadzai, David Broadbent, Christopher Occhiuto, Canchai Yang, Rupali Das, Hariharan Subramanian
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 propagate, rather than terminate, intracellular signal transduction cascades. Because β-arrestins are promiscuous in their binding, they are capable of interacting with several different GPCRs and downstream effectors; in doing so, they vastly expand the repertoire of cellular responses evoked by agonist binding and the scope of responses that may contribute to inflammation during infectious and sterile insults...
2017: Advances in Immunology
Michael D Steury, Laura R McCabe, Narayanan Parameswaran
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 physiological and pathophysiological processes including chemotaxis, signaling, migration, inflammatory gene expression, etc...
2017: Advances in Immunology
Anjali Gupta, Varsha Singh
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...
2017: Advances in Immunology
Hsi-Hsien Lin, Cheng-Chih Hsiao, Caroline Pabst, Josée Hébert, Torsten Schöneberg, Jörg Hamann
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 mechanisms of activation and signal transduction have emerged only recently...
2017: Advances in Immunology
Hydar Ali
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 important feature of MCTC is that they selectively express MRGPRX2...
2017: Advances in Immunology
Yassine Amrani, Peter Bradding
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 chapter, we will review the experimental evidence that describes the different potential factors and associated mechanisms that can blunt the therapeutic action of β2-adrenoceptor agonists in asthma...
2017: Advances in Immunology
Xing Liu, Judy Lieberman
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...
2017: Advances in Immunology
Jessy Presumey, Allison R Bialas, Michael C Carroll
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...
2017: Advances in Immunology
Carly E Gregor, Jade Foeng, Iain Comerford, Shaun R McColl
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...
2017: Advances in Immunology
Sudipta Das, Marina Miller, David H Broide
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...
2017: Advances in Immunology
Dalia Pakalniškytė, Barbara U Schraml
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...
2017: Advances in Immunology
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