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Clinical Immunology (Orlando, Fla.) Nov 2018Aging of the immune system in humans and animals is characterized by a decline in both adaptive and innate immune responses. Paradoxically, aging is also associated with... (Review)
Review
Aging of the immune system in humans and animals is characterized by a decline in both adaptive and innate immune responses. Paradoxically, aging is also associated with a state of chronic inflammation ("inflammaging") and an increased likelihood of developing autoimmune diseases. Epigenetic changes in non-dividing and dividing cells, including immune cells, due to environmental factors contribute to the inflammation and autoimmunity that characterize both the state and diseases of aging. Here, we review the epigenetic mechanisms involved in the development of immune senescence and autoimmunity in old age.
Topics: Adaptive Immunity; Aging; Autoimmune Diseases; Autoimmunity; Epigenesis, Genetic; Humans; Immunity, Innate; Immunosenescence; Inflammation
PubMed: 29654845
DOI: 10.1016/j.clim.2018.04.002 -
Circulation Research Jan 2018Platelets, non-nucleated blood components first described over 130 years ago, are recognized as the primary cell regulating hemostasis and thrombosis. The vascular... (Review)
Review
Platelets, non-nucleated blood components first described over 130 years ago, are recognized as the primary cell regulating hemostasis and thrombosis. The vascular importance of platelets has been attributed to their essential role in thrombosis, mediating myocardial infarction, stroke, and venous thromboembolism. Increasing knowledge on the platelets' role in the vasculature has led to many advances in understanding not only how platelets interact with the vessel wall but also how they convey changes in the environment to other circulating cells. In addition to their well-described hemostatic function, platelets are active participants in the immune response to microbial organisms and foreign substances. Although incompletely understood, the immune role of platelets is a delicate balance between its pathogenic response and its regulation of thrombotic and hemostatic functions. Platelets mediate complex vascular homeostasis via specific receptors and granule release, RNA transfer, and mitochondrial secretion that subsequently regulates hemostasis and thrombosis, infection, and innate and adaptive immunity.
Topics: Adaptive Immunity; Animals; Blood Platelets; Hemostasis; Humans; Immunity, Cellular; Immunity, Innate; Inflammation; Platelet Aggregation Inhibitors; Thrombosis
PubMed: 29348254
DOI: 10.1161/CIRCRESAHA.117.310795 -
Periodontology 2000 Feb 2014The pathogenesis of periodontitis involves a complex immune/inflammatory cascade that is initiated by the bacteria of the oral biofilm that forms naturally on the teeth.... (Review)
Review
The pathogenesis of periodontitis involves a complex immune/inflammatory cascade that is initiated by the bacteria of the oral biofilm that forms naturally on the teeth. The susceptibility to periodontitis appears to be determined by the host response; specifically, the magnitude of the inflammatory response and the differential activation of immune pathways. The purpose of this review was to delineate our current knowledge of the host response in periodontitis. The role of innate immunity, the failure of acute inflammation to resolve (thus becoming chronic), the cytokine pathways that regulate the activation of acquired immunity and the cells and products of the immune system are considered. New information relating to regulation of both inflammation and the immune response will be reviewed in the context of susceptibility to, and perhaps control of, periodontitis.
Topics: Adaptive Immunity; Bacteria; Biofilms; Cytokines; Disease Susceptibility; Host-Pathogen Interactions; Humans; Immunity, Cellular; Immunity, Humoral; Immunity, Innate; Inflammation; Periodontitis
PubMed: 24320956
DOI: 10.1111/prd.12002 -
Biomedicine & Pharmacotherapy =... Dec 2020Coronaviruses (CoVs) are a member of the Coronaviridae family with positive-sense single- stranded RNA. In recent years, the CoVs have become a global problem to public... (Review)
Review
Coronaviruses (CoVs) are a member of the Coronaviridae family with positive-sense single- stranded RNA. In recent years, the CoVs have become a global problem to public health. The immune responses (innate and adaptive immunity) are essential for elimination and clearance of CoVs infections, however, uncontrolled immune responses can result in aggravating acute lung injury and significant immunopathology. Gaining profound understanding about the interaction between CoVs and the innate and adaptive immune systems could be a critical step in the field of treatment. In this review, we present an update on the host innate and adaptive immune responses against SARS-CoV, MERS-CoV and newly appeared SARS-CoV-2.
Topics: Adaptive Immunity; Animals; Antibodies, Monoclonal; COVID-19; Humans; Immunity, Innate; Immunization, Passive; SARS-CoV-2; Virus Replication; COVID-19 Serotherapy
PubMed: 33120236
DOI: 10.1016/j.biopha.2020.110859 -
Frontiers in Immunology 2020The risk and severity of specific infections are increased during pregnancy due to a combination of physiological and immunological changes. Characterizing the maternal... (Review)
Review
The risk and severity of specific infections are increased during pregnancy due to a combination of physiological and immunological changes. Characterizing the maternal immune system during pregnancy is important to understand how the maternal immune system maintains tolerance towards the allogeneic fetus. This may also inform strategies to prevent maternal fatalities due to infections and optimize maternal vaccination to best protect the mother-fetus dyad and the infant after birth. In this review, we describe what is known about the immunological changes that occur during a normal pregnancy.
Topics: Adaptive Immunity; Animals; Female; Histocompatibility, Maternal-Fetal; Humans; Immune System; Immunity, Cellular; Immunity, Humoral; Immunity, Innate; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications
PubMed: 33133091
DOI: 10.3389/fimmu.2020.575197 -
Seminars in Nephrology Nov 2013Complement is an important component of the innate immune system that is crucial for defense from microbial infections and for clearance of immune complexes and injured... (Review)
Review
Complement is an important component of the innate immune system that is crucial for defense from microbial infections and for clearance of immune complexes and injured cells. In normal conditions complement is tightly controlled by a number of fluid-phase and cell surface proteins to avoid injury to autologous tissues. When complement is hyperactivated, as occurs in autoimmune diseases or in subjects with dysfunctional regulatory proteins, it drives a severe inflammatory response in numerous organs. The kidney appears to be particularly vulnerable to complement-mediated inflammatory injury. Injury may derive from deposition of circulating active complement fragments in glomeruli, but complement locally produced and activated in the kidney also may have a role. Many kidney disorders have been linked to abnormal complement activation, including immune-complex-mediated glomerulonephritis and rare genetic kidney diseases, but also tubulointerstitial injury associated with progressive proteinuric diseases or ischemia-reperfusion.
Topics: Adaptive Immunity; Complement Activating Enzymes; Complement Activation; Complement System Proteins; Humans; Immunity, Innate; Kidney Diseases
PubMed: 24161035
DOI: 10.1016/j.semnephrol.2013.08.001 -
Annual Review of Immunology 2014The immune system defends against pathogens and maintains tissue homeostasis for the life of the organism. These diverse functions are bioenergetically expensive,... (Review)
Review
The immune system defends against pathogens and maintains tissue homeostasis for the life of the organism. These diverse functions are bioenergetically expensive, requiring precise control of cellular metabolic pathways. Although initial observations in this area were made almost a century ago, studies over the past decade have elucidated the molecular basis for how extracellular signals control the uptake and catabolism of nutrients in quiescent and activated immune cells. Collectively, these studies have revealed that the metabolic pathways of oxidative metabolism, glycolysis, and glutaminolysis preferentially fuel the cell fate decisions and effector functions of immune cells. Here, we discuss these findings and provide a general framework for understanding how metabolism fuels and regulates the maturation of immune responses. A better understanding of the metabolic checkpoints that control these transitions might provide new insights for modulating immunity in infection, cancer, or inflammatory disorders.
Topics: Adaptive Immunity; Animals; Humans; Immune System; Immunity; Immunity, Innate; Metabolic Networks and Pathways
PubMed: 24655299
DOI: 10.1146/annurev-immunol-032713-120236 -
The Journal of Allergy and Clinical... Jan 2023T cells are critical orchestrators of the adaptive immune response that optimally eliminate a specific pathogen. Aberrant T-cell development and function are implicated... (Review)
Review
T cells are critical orchestrators of the adaptive immune response that optimally eliminate a specific pathogen. Aberrant T-cell development and function are implicated in a broad range of human disease including immunodeficiencies, autoimmune diseases, and allergic diseases. Accordingly, therapies targeting T cells and their effector cytokines have markedly improved the care of patients with immune dysregulatory diseases. Newer discoveries concerning T-cell-mediated antitumor immunity and T-cell exhaustion have further prompted development of highly effective and novel treatment modalities for malignancies, including checkpoint inhibitors and antigen-reactive T cells. Recent discoveries are also uncovering the depth and variability of T-cell phenotypes: while T cells have long been described using a subset-based classification system, next-generation sequencing technologies suggest an astounding degree of complexity and heterogeneity at the single-cell level.
Topics: Humans; T-Lymphocytes; Neoplasms; Adaptive Immunity; Cytokines; Immunity, Cellular; CD8-Positive T-Lymphocytes
PubMed: 36272581
DOI: 10.1016/j.jaci.2022.10.011 -
Nature Reviews. Clinical Oncology May 2021The immune system has crucial roles in cancer development and treatment. Whereas adaptive immunity can prevent or constrain cancer through immunosurveillance, innate... (Review)
Review
The immune system has crucial roles in cancer development and treatment. Whereas adaptive immunity can prevent or constrain cancer through immunosurveillance, innate immunity and inflammation often promote tumorigenesis and malignant progression of nascent cancer. The past decade has witnessed the translation of knowledge derived from preclinical studies of antitumour immunity into clinically effective, approved immunotherapies for cancer. By contrast, the successful implementation of treatments that target cancer-associated inflammation is still awaited. Anti-inflammatory agents have the potential to not only prevent or delay cancer onset but also to improve the efficacy of conventional therapeutics and next-generation immunotherapies. Herein, we review the current clinical advances and experimental findings supporting the utility of an anti-inflammatory approach to the treatment of solid malignancies. Gaining a better mechanistic understanding of the mode of action of anti-inflammatory agents and designing more effective treatment combinations would advance the clinical application of this therapeutic approach.
Topics: Adaptive Immunity; Anti-Inflammatory Agents; Carcinogenesis; Humans; Immunity, Innate; Immunotherapy; Inflammation; Monitoring, Immunologic; Neoplasms
PubMed: 33469195
DOI: 10.1038/s41571-020-00459-9 -
Journal For Immunotherapy of Cancer Sep 2020To prevent the destruction of tissues owing to excessive and/or inappropriate immune responses, immune cells are under strict check by various regulatory mechanisms at... (Review)
Review
To prevent the destruction of tissues owing to excessive and/or inappropriate immune responses, immune cells are under strict check by various regulatory mechanisms at multiple points. Inhibitory coreceptors, including programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), serve as critical checkpoints in restricting immune responses against self-tissues and tumor cells. Immune checkpoint inhibitors that block PD-1 and CTLA-4 pathways significantly improved the outcomes of patients with diverse cancer types and have revolutionized cancer treatment. However, response rates to such therapies are rather limited, and immune-related adverse events are also observed in a substantial patient population, leading to the urgent need for novel therapeutics with higher efficacy and lower toxicity. In addition to PD-1 and CTLA-4, a variety of stimulatory and inhibitory coreceptors are involved in the regulation of T cell activation. Such coreceptors are listed as potential drug targets, and the competition to develop novel immunotherapies targeting these coreceptors has been very fierce. Among such coreceptors, lymphocyte activation gene-3 (LAG-3) is expected as the foremost target next to PD-1 in the development of cancer therapy, and multiple clinical trials testing the efficacy of LAG-3-targeted therapy are underway. LAG-3 is a type I transmembrane protein with structural similarities to CD4. Accumulating evidence indicates that LAG-3 is an inhibitory coreceptor and plays pivotal roles in autoimmunity, tumor immunity, and anti-infection immunity. In this review, we summarize the current understanding of LAG-3, ranging from its discovery to clinical application.
Topics: Adaptive Immunity; Amino Acids; Caenorhabditis elegans Proteins; Humans; Immunotherapy; Transcription Factors
PubMed: 32929051
DOI: 10.1136/jitc-2020-001014