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    903 results match your criteria Annual Review of Immunology[Journal]

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    The Formation and Function of Granulomas.
    Annu Rev Immunol 2018 Feb 5. Epub 2018 Feb 5.
    Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, United Kingdom; email: ,
    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. Read More

    Apoptosis and Clearance of Apoptotic Cells.
    Annu Rev Immunol 2018 Feb 5. Epub 2018 Feb 5.
    Laboratory of Biochemistry and Immunology, World Premier International Research Center Initiative Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan; email:
    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. Read More

    IgA Function in Relation to the Intestinal Microbiota.
    Annu Rev Immunol 2018 Jan 26. Epub 2018 Jan 26.
    Maurice Müller Laboratories (Department of Biomedical Research), University of Bern, 3008 Bern, Switzerland.
    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. Read More

    Antigen Presentation by Extracellular Vesicles from Professional Antigen-Presenting Cells.
    Annu Rev Immunol 2018 Jan 31. Epub 2018 Jan 31.
    Department Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, NL-3508 TD Utrecht, The Netherlands; email:
    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. Read More

    Genetics of Natural Killer Cells in Human Health, Disease, and Survival.
    Annu Rev Immunol 2018 Feb 2. Epub 2018 Feb 2.
    Department of Structural Biology and Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, California 94305, USA; email: ,
    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. Read More

    Self-Reactive B Cells in the Germinal Center Reaction.
    Annu Rev Immunol 2018 Jan 22. Epub 2018 Jan 22.
    Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010 Australia; email: ,
    Maintenance of immunological self-tolerance requires lymphocytes carrying self-reactive antigen receptors to be selectively prevented from mounting destructive or inflammatory effector responses. Classically, self-tolerance is viewed in terms of the removal, editing, or silencing of B and T cells that have formed self-reactive antigen receptors during their early development. However, B cells activated by foreign antigen can enter germinal centers (GCs), where they further modify their antigen receptor by somatic hypermutation (SHM) of their immunoglobulin genes. Read More

    Immune Response to Dengue and Zika.
    Annu Rev Immunol 2018 01 18. Epub 2018 Jan 18.
    Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA; email:
    Flaviviruses such as dengue (DENV), yellow fever (YFV), West Nile (WNV), and Zika (ZIKV) are human pathogens of global significance. In particular, DENV causes the most prevalent mosquito-borne viral diseases in humans, and ZIKV emerged from obscurity into the spotlight in 2016 as the etiologic agent of congenital Zika syndrome. Owing to the recent emergence of ZIKV as a global pandemic threat, the roles of the immune system during ZIKV infections are as yet unclear. Read More

    Immune Responses to Retroviruses.
    Annu Rev Immunol 2018 Jan 12. Epub 2018 Jan 12.
    Immunity and Cancer Department, INSERM U932, Institut Curie, PSL Research University, 75005 Paris, France; email:
    Retroviruses are genome invaders that have shared a long history of coevolution with vertebrates and their immune system. Found endogenously in genomes as traces of past invasions, retroviruses are also considerable threats to human health when they exist as exogenous viruses such as HIV. The immune response to retroviruses is engaged by germline-encoded sensors of innate immunity that recognize viral components and damage induced by the infection. Read More

    Connections Between Metabolism and Epigenetics in Programming Cellular Differentiation.
    Annu Rev Immunol 2018 Jan 12. Epub 2018 Jan 12.
    Department of Microbiology, University of Alabama at Birmingham, Alabama 35294, USA; email: ,
    Researchers are intensifying efforts to understand the mechanisms by which changes in metabolic states influence differentiation programs. An emerging objective is to define how fluctuations in metabolites influence the epigenetic states that contribute to differentiation programs. This is because metabolites such as S-adenosylmethionine, acetyl-CoA, α-ketoglutarate, 2-hydroxyglutarate, and butyrate are donors, substrates, cofactors, and antagonists for the activities of epigenetic-modifying complexes and for epigenetic modifications. Read More

    Immune Responses in the Liver.
    Annu Rev Immunol 2018 Jan 12. Epub 2018 Jan 12.
    Calvin, Phoebe & Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, T2N 4N1, Canada; email: ,
    The liver is a key, frontline immune tissue. Ideally positioned to detect pathogens entering the body via the gut, the liver appears designed to detect, capture, and clear bacteria, viruses, and macromolecules. Containing the largest collection of phagocytic cells in the body, this organ is an important barrier between us and the outside world. Read More

    Cell Biology of T Cell Receptor Expression and Regulation.
    Annu Rev Immunol 2017 Dec 20. Epub 2017 Dec 20.
    Lymphocyte Cell Biology Unit, INSERM U1221, Department of Immunology, Institut Pasteur, Paris 75015, France; email: ,
    T cell receptors (TCRs) are protein complexes formed by six different polypeptides. In most T cells, TCRs are composed of αβ subunits displaying immunoglobulin-like variable domains that recognize peptide antigens associated with major histocompatibility complex molecules expressed on the surface of antigen-presenting cells. TCR αβ subunits are associated with the CD3 complex formed by the γ, δ, ε, and ζ subunits, which are invariable and ensure signal transduction. Read More

    ZAP-70 in Signaling, Biology, and Disease.
    Annu Rev Immunol 2017 Dec 13. Epub 2017 Dec 13.
    Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Rheumatology Research Center, University of California, San Francisco, California 94143, USA; email: ,
    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. Read More

    Host Control of Fungal Infections: Lessons from Basic Studies and Human Cohorts.
    Annu Rev Immunol 2017 Dec 13. Epub 2017 Dec 13.
    Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605; email:
    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. This review synthesizes immunological knowledge derived from basic mouse studies and from human cohorts and provides an overview of mammalian antifungal host defenses that show promise for informing therapeutic and vaccination strategies for vulnerable patients. Read More

    Human T Cell Leukemia Virus Type 1: Persistence and Pathogenesis.
    Annu Rev Immunol 2017 Nov 16. Epub 2017 Nov 16.
    Division of Infectious Diseases, Faculty of Medicine, Imperial College, London W2 1PG, United Kingdom; email:
    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. Read More

    Evolution of Alternative Adaptive Immune Systems in Vertebrates.
    Annu Rev Immunol 2017 Nov 16. Epub 2017 Nov 16.
    Emory Vaccine Center and Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia 30322, USA; email: , ,
    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. Read More

    Autophagy and Inflammation.
    Annu Rev Immunol 2017 Nov 16. Epub 2017 Nov 16.
    Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York 10016, USA; email: ,
    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. Read More

    Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities.
    Annu Rev Immunol 2017 Apr;35:229-253
    Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158; email:
    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. Read More

    Metabolite-Sensing G Protein-Coupled Receptors-Facilitators of Diet-Related Immune Regulation.
    Annu Rev Immunol 2017 Apr;35:371-402
    Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia; email: , , ,
    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. Read More

    Signaling by Antibodies: Recent Progress.
    Annu Rev Immunol 2017 Apr;35:285-311
    Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10065; email:
    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. Read More

    A Perspective on the Role of Computational Models in Immunology.
    Annu Rev Immunol 2017 Apr 6;35:403-439. Epub 2017 Feb 6.
    Institute for Medical Engineering and Science, Departments of Chemical Engineering, Physics, Chemistry, and Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; email:
    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. Read More

    Antigen-Presenting Cells in the Skin.
    Annu Rev Immunol 2017 Apr 6;35:469-499. Epub 2017 Feb 6.
    Department of Dermatology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261; email:
    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. Read More

    Protective and Harmful Immunity to RSV Infection.
    Annu Rev Immunol 2017 Apr 6;35:501-532. Epub 2017 Feb 6.
    Respiratory Infections, National Heart and Lung Institute, Imperial College London, London W2 1PG, United Kingdom; email:
    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. Read More

    Microglia Function in the Central Nervous System During Health and Neurodegeneration.
    Annu Rev Immunol 2017 Apr 9;35:441-468. Epub 2017 Feb 9.
    Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; email:
    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. Read More

    Thymic Epithelial Cells.
    Annu Rev Immunol 2017 Apr 10;35:85-118. Epub 2017 Feb 10.
    MRC Centre for Immune Regulation, Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, United Kingdom; email:
    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. Read More

    Disorders of the JAK/STAT Pathway in T Cell Lymphoma Pathogenesis: Implications for Immunotherapy.
    Annu Rev Immunol 2017 Apr 9;35:533-550. Epub 2017 Feb 9.
    Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; email:
    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. Read More

    Memory B Cells of Mice and Humans.
    Annu Rev Immunol 2017 Apr 30;35:255-284. Epub 2017 Jan 30.
    Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261; email: ,
    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. Read More

    Intracellular Nucleic Acid Detection in Autoimmunity.
    Annu Rev Immunol 2017 Apr 30;35:313-336. Epub 2017 Jan 30.
    Department of Immunology, University of Washington School of Medicine, Seattle, Washington 98109; email:
    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. Read More

    Microbes and Cancer.
    Annu Rev Immunol 2017 Apr 30;35:199-228. Epub 2017 Jan 30.
    Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, email:
    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. Read More

    Understanding Human Autoimmunity and Autoinflammation Through Transcriptomics.
    Annu Rev Immunol 2017 Apr 30;35:337-370. Epub 2017 Jan 30.
    Baylor Institute for Immunology Research, Dallas, Texas 75204; email: , ,
    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. Read More

    Immunobiology of Long Noncoding RNAs.
    Annu Rev Immunol 2017 Apr 11;35:177-198. Epub 2017 Jan 11.
    Program in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605; email:
    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. Read More

    Mucosal Ecological Network of Epithelium and Immune Cells for Gut Homeostasis and Tissue Healing.
    Annu Rev Immunol 2017 Apr 11;35:119-147. Epub 2017 Jan 11.
    Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; email:
    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. Read More

    The Biology and Underlying Mechanisms of Cross-Presentation of Exogenous Antigens on MHC-I Molecules.
    Annu Rev Immunol 2017 Apr 11;35:149-176. Epub 2017 Jan 11.
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655; email: , , , ,
    To monitor the health of cells, the immune system tasks antigen-presenting cells with gathering antigens from other cells and bringing them to CD8 T cells in the form of peptides bound to MHC-I molecules. Most cells would be unable to perform this function because they use their MHC-I molecules to exclusively present peptides derived from the cell's own proteins. However, the immune system evolved mechanisms for dendritic cells and some other phagocytes to sample and present antigens from the extracellular milieu on MHC-I through a process called cross-presentation. Read More

    Th2 Cells in Health and Disease.
    Annu Rev Immunol 2017 Apr 28;35:53-84. Epub 2016 Nov 28.
    Department of Otorhinolaryngology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
    Helper T (Th) cell subsets direct immune responses by producing signature cytokines. Th2 cells produce IL-4, IL-5, and IL-13, which are important in humoral immunity and protection from helminth infection and are central to the pathogenesis of many allergic inflammatory diseases. Molecular analysis of Th2 cell differentiation and maintenance of function has led to recent discoveries that have refined our understanding of Th2 cell biology. Read More

    Genetics of Infectious and Inflammatory Diseases: Overlapping Discoveries from Association and Exome-Sequencing Studies.
    Annu Rev Immunol 2017 Apr 1;35:1-30. Epub 2016 Dec 1.
    McGill University Research Centre on Complex Traits, McGill University, Montreal, Quebec H3G 0B1, Canada; email: , ,
    Genome technologies have defined a complex genetic architecture in major infectious, inflammatory, and autoimmune disorders. High density marker arrays and Immunochips have powered genome-wide association studies (GWAS) that have mapped nearly 450 genetic risk loci in 22 major inflammatory diseases, including a core of common genes that play a central role in pathological inflammation. Whole-exome and whole-genome sequencing have identified more than 265 genes in which mutations cause primary immunodeficiencies and rare forms of severe inflammatory bowel disease. Read More

    The Lymphatic System: Integral Roles in Immunity.
    Annu Rev Immunol 2017 Apr 14;35:31-52. Epub 2016 Nov 14.
    Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida 33612.
    The lymphatic vasculature is not considered a formal part of the immune system, but it is critical to immunity. One of its major roles is in the coordination of the trafficking of antigen and immune cells. However, other roles in immunity are emerging. Read More

    Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design.
    Annu Rev Immunol 2016 May;34:635-59
    Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037; email: ,
    HIV employs multiple means to evade the humoral immune response, particularly the elicitation of and recognition by broadly neutralizing antibodies (bnAbs). Such antibodies can act antivirally against a wide spectrum of viruses by targeting relatively conserved regions on the surface HIV envelope trimer spike. Elicitation of and recognition by bnAbs are hindered by the arrangement of spikes on virions and the relatively difficult access to bnAb epitopes on spikes, including the proximity of variable regions and a high density of glycans. Read More

    Tissue Tregs.
    Annu Rev Immunol 2016 May;34:609-33
    Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115; email: , ,
    The immune system is responsible for defending an organism against the myriad of microbial invaders it constantly confronts. It has become increasingly clear that the immune system has a second major function: the maintenance of organismal homeostasis. Foxp3(+)CD4(+) regulatory T cells (Tregs) are important contributors to both of these critical activities, defense being the primary purview of Tregs circulating through lymphoid organs, and homeostasis ensured mainly by their counterparts residing in parenchymal tissues. Read More

    Exploiting Mucosal Immunity for Antiviral Vaccines.
    Annu Rev Immunol 2016 May;34:575-608
    Howard Hughes Medical Institute, Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520; email:
    Mucosal surfaces provide a remarkably effective barrier against potentially dangerous pathogens. Therefore, enhancing mucosal immunity through vaccines-strengthening that first line of defense-holds significant promise for reducing the burden of viral diseases. The large and varied class of viral pathogens, however, continues to present thorny challenges to vaccine development. Read More

    Protein Kinase C Enzymes in the Hematopoietic and Immune Systems.
    Annu Rev Immunol 2016 May;34:511-38
    Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037; email: ,
    The protein kinase C (PKC) family, discovered in the late 1970s, is composed of at least 10 serine/threonine kinases, divided into three groups based on their molecular architecture and cofactor requirements. PKC enzymes have been conserved throughout evolution and are expressed in virtually all cell types; they represent critical signal transducers regulating cell activation, differentiation, proliferation, death, and effector functions. PKC family members play important roles in a diverse array of hematopoietic and immune responses. Read More

    Fate Mapping and Quantitation of Hematopoiesis In Vivo.
    Annu Rev Immunol 2016 May;34:449-78
    Division of Cellular Immunology, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany; email:
    Hematopoietic stem cells (HSCs) and downstream progenitors have long been studied based on phenotype, cell purification, proliferation, and transplantation into myeloablated recipients. These experiments, complemented by data on expression profiles, mouse mutants, and humans with hematopoietic defects, are the foundation for the current hematopoietic differentiation tree. However, there are fundamental gaps in our knowledge of the quantitative and qualitative operation of the HSC/progenitor system under physiological and pathological conditions in vivo. Read More

    Retinoic Acid and Retinoic Acid Receptors as Pleiotropic Modulators of the Immune System.
    Annu Rev Immunol 2016 May;34:369-94
    Division of Developmental Immunology, La Jolla Institute for Allergy & Immunology, La Jolla, California 92037; email: ,
    Vitamin A is a multifunctional vitamin implicated in a wide range of biological processes. Its control over the immune system and functions are perhaps the most pleiotropic not only for development but also for the functional fate of almost every cell involved in protective or regulatory adaptive or innate immunity. This is especially key at the intestinal border, where dietary vitamin A is first absorbed. Read More

    Heterogeneity of Human CD4(+) T Cells Against Microbes.
    Annu Rev Immunol 2016 May;34:317-34
    Center of Medical Immunology and Laboratory of Cellular Immunology, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland; email:
    CD4(+) T helper (Th) cells play a central role in the adaptive immune response by providing help to B cells and cytotoxic T cells and by releasing different types of cytokines in tissues to mediate protection against a wide range of pathogenic microorganisms. These functions are performed by different types of Th cells endowed with distinct migratory capacities and effector functions. Here we discuss how studies of the human T cell response to microbes have advanced our understanding of Th cell functional heterogeneity, in particular with the discovery of a distinct Th1 subset involved in the response to Mycobacteria and the characterization of two types of Th17 cells specific for extracellular bacteria or fungi. Read More

    The Innate Lymphoid Cell Precursor.
    Annu Rev Immunol 2016 May;34:299-316
    Committee on Immunology, The University of Chicago, Illinois 60637; email:
    The discovery of tissue-resident innate lymphoid cell populations effecting different forms of type 1, 2, and 3 immunity; tissue repair; and immune regulation has transformed our understanding of mucosal immunity and allergy. The emerging complexity of these populations along with compounding issues of redundancy and plasticity raise intriguing questions about their precise lineage relationship. Here we review advances in mapping the emergence of these lineages from early lymphoid precursors. Read More

    Mechanisms of Pediatric Inflammatory Bowel Disease.
    Annu Rev Immunol 2016 May;34:31-64
    Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease and.
    Inflammatory bowel disease (IBD), including Crohn disease and ulcerative colitis, is characterized by chronic intestinal inflammation due to a complex interaction of genetic determinants, disruption of mucosal barriers, aberrant inflammatory signals, loss of tolerance, and environmental triggers. Importantly, the incidence of pediatric IBD is rising, particularly in children younger than 10 years. In this review, we discuss the clinical presentation of these patients and highlight environmental exposures that may affect disease risk, particularly among people with a background genetic risk. Read More

    How One Thing Led to Another.
    Annu Rev Immunol 2016 May;34:1-30
    Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, and Ludwig Center for Cancer Stem Cell Research and Medicine at Stanford, Stanford, CA 94305.
    I started research in high school, experimenting on immunological tolerance to transplantation antigens. This led to studies of the thymus as the site of maturation of T cells, which led to the discovery, isolation, and clinical transplantation of purified hematopoietic stem cells (HSCs). The induction of immune tolerance with HSCs has led to isolation of other tissue-specific stem cells for regenerative medicine. Read More

    Coinhibitory Pathways in Immunotherapy for Cancer.
    Annu Rev Immunol 2016 May 25;34:539-73. Epub 2016 Feb 25.
    Department of Microbiology and Immunobiology, and Evergrande Center for Immunologic Diseases, Harvard Medical School, Boston, Massachusetts 02115; email:
    The immune system is capable of recognizing tumors and eliminates many early malignant cells. However, tumors evolve to evade immune attack, and the tumor microenvironment is immunosuppressive. Immune responses are regulated by a number of immunological checkpoints that promote protective immunity and maintain tolerance. Read More

    The Immunology of CD1- and MR1-Restricted T Cells.
    Annu Rev Immunol 2016 May 25;34:479-510. Epub 2016 Feb 25.
    Department of Biomedicine, Basel University Hospital and Basel University, CH-4031 Basel, Switzerland; email: , ,
    CD1- and MHC-related molecule-1 (MR1)-restricted T lymphocytes recognize nonpeptidic antigens, such as lipids and small metabolites, and account for a major fraction of circulating and tissue-resident T cells. They represent a readily activated, long-lasting population of effector cells and contribute to the early phases of immune response, orchestrating the function of other cells. This review addresses the main aspects of their immunological functions, including antigen and T cell receptor repertoires, mechanisms of nonpeptidic antigen presentation, and the current evidence for their participation in human and experimental diseases. Read More

    Galectins and Immune Responses-Just How Do They Do Those Things They Do?
    Annu Rev Immunol 2016 May 22;34:243-64. Epub 2016 Feb 22.
    Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California 90095; email: ,
    Galectins are a family of mammalian carbohydrate-binding proteins expressed by many cell types. Galectins can function intracellularly and can also be secreted to bind to cell surface glycoconjugate counterreceptors. Some galectins are made by immune cells, whereas other galectins are secreted by different cell types, such as endothelial or epithelial cells, and bind to immune cells to regulate immune responses. Read More

    Chemokines and Chemokine Receptors in Lymphoid Tissue Dynamics.
    Annu Rev Immunol 2016 May 22;34:203-42. Epub 2016 Feb 22.
    Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany; email:
    The continuous migration of immune cells between lymphoid and nonlymphoid organs is a key feature of the immune system, facilitating the distribution of effector cells within nearly all compartments of the body. Furthermore, reaching their correct position within primary, secondary, or tertiary lymphoid organs is a prerequisite to ensure immune cells' unimpaired differentiation, maturation, and selection, as well as their activation or functional silencing. The superfamilies of chemokines and chemokine receptors are of major importance in guiding immune cells to and within lymphoid and nonlymphoid tissues. Read More

    Follicular Helper T Cells.
    Annu Rev Immunol 2016 May 22;34:335-68. Epub 2016 Feb 22.
    School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom.
    Although T cell help for B cells was described several decades ago, it was the identification of CXCR5 expression by B follicular helper T (Tfh) cells and the subsequent discovery of their dependence on BCL6 that led to the recognition of Tfh cells as an independent helper subset and accelerated the pace of discovery. More than 20 transcription factors, together with RNA-binding proteins and microRNAs, control the expression of chemotactic receptors and molecules important for the function and homeostasis of Tfh cells. Tfh cells prime B cells to initiate extrafollicular and germinal center antibody responses and are crucial for affinity maturation and maintenance of humoral memory. Read More

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