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Advances in Immunology

Jonathan Chow, Jonathan C Kagan
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, IMD signaling, and autophagy...
2018: Advances in Immunology
James Muller, Audrey Baeyens, Michael L Dustin
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...
2018: Advances in Immunology
Hidetoshi Nakagawa, Lei Wang, Harvey Cantor, Hye-Jung Kim
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...
2018: Advances in Immunology
Sherry G Lin, Zhaoqing Ba, Frederick W Alt, Yu Zhang
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...
2018: Advances in Immunology
Masayuki Kuraoka, Eric Meffre, Garnett Kelsoe
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...
2018: Advances in Immunology
Wilbur M Song, Marco Colonna
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...
2018: Advances in Immunology
William A Comrie, Michael J Lenardo
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 pathogens or mild autoimmune conditions...
2018: Advances in Immunology
Rod A Rahimi, Andrew D Luster
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...
2018: Advances in Immunology
Erin E West, Behdad Afzali, Claudia Kemper
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...
2018: Advances in Immunology
Rudolf Valenta, Alexander Karaulov, Verena Niederberger, Pia Gattinger, Marianne van Hage, Sabine Flicker, Birgit Linhart, Raffaela Campana, Margarete Focke-Tejkl, Mirela Curin, Julia Eckl-Dorna, Christian Lupinek, Yvonne Resch-Marat, Susanne Vrtala, Irene Mittermann, Victoria Garib, Musa Khaitov, Peter Valent, Winfried F Pickl
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...
2018: Advances in Immunology
Patricia C Fulkerson, Marc E Rothenberg
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...
2018: 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
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