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Nature Reviews. Immunology Jun 2020Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent... (Review)
Review
Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent triggers. This process has been termed 'trained immunity', a de facto innate immune memory. Research in the past decade has pointed to the broad benefits of trained immunity for host defence but has also suggested potentially detrimental outcomes in immune-mediated and chronic inflammatory diseases. Here we define 'trained immunity' as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity.
Topics: Adaptive Immunity; Animals; Epigenesis, Genetic; Humans; Immune System; Immune System Diseases; Immune Tolerance; Immunity, Innate; Immunologic Memory; Inflammation
PubMed: 32132681
DOI: 10.1038/s41577-020-0285-6 -
Current Opinion in Immunology Aug 2022The concept that only adaptive immunity can build immunological memory has been challenged in the past decade. Live attenuated vaccines such as the Bacillus... (Review)
Review
The concept that only adaptive immunity can build immunological memory has been challenged in the past decade. Live attenuated vaccines such as the Bacillus Calmette-Guérin, measles-containing vaccines, and the oral polio vaccine have been shown to reduce overall mortality beyond their effects attributable to the targeted diseases. After an encounter with a primary stimulus, epigenetic and metabolic reprogramming of bone marrow progenitor cells and functional changes of tissue immune cell populations result in augmented immune responses against a secondary challenge. This process has been termed trained immunity. This review describes the mechanisms leading to trained immunity and summarizes the most important developments from the past few years.
Topics: Adaptive Immunity; BCG Vaccine; Humans; Immunity, Innate; Immunologic Memory; Mycobacterium bovis; Vaccination
PubMed: 35597182
DOI: 10.1016/j.coi.2022.102190 -
Redox Biology Oct 2020Innate and adaptive immune cell activation and infiltration is the key characteristic of tissue inflammation. The innate immune system is the front line of host defense... (Review)
Review
Innate and adaptive immune cell activation and infiltration is the key characteristic of tissue inflammation. The innate immune system is the front line of host defense in which innate immune cells are activated by danger signals, including pathogen- and danger-associated molecular pattern, and metabolite-associated danger signal. Innate immunity activation can directly contribute to tissue inflammation or immune resolution by phagocytosis and secretion of biologically active molecules, or indirectly via antigen-presenting cell (APC) activation-mediated adaptive immune responses. This review article describes the cellular and molecular interplay of innate-adaptive immune systems. Three major mechanisms are emphasized in this article for their role in facilitating innate-adaptive immunity interplay. 1) APC can be formed from classical and conditional innate immune cells to bridge innate-adaptive immune response. 2) Immune checkpoint molecular pairs connect innate and adaptive immune cells to direct one-way and two-way immune checkpoint reactions. 3) Metabolic reprogramming during immune responses leads to excessive cytosolic and mitochondrial reactive oxygen species (ROS) production. Increased NADPH oxidase-derived extracellular and intracellular ROS are mostly responsible for oxidative stress, which contributes to functional changes in immune cells. Further understanding of innate-adaptive immunity interplay and its underlying molecular basis would lead to the identification of therapeutic targets for immunological and inflammatory disease.
Topics: Adaptive Immunity; Humans; Immune System; Immunity, Innate; Inflammation; Oxidation-Reduction
PubMed: 33086106
DOI: 10.1016/j.redox.2020.101759 -
Cell Mar 2018In bacteria and archaea, clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins constitute an adaptive immune system... (Review)
Review
In bacteria and archaea, clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins constitute an adaptive immune system against phages and other foreign genetic elements. Here, we review the biology of the diverse CRISPR-Cas systems and the major progress achieved in recent years in understanding the underlying mechanisms of the three stages of CRISPR-Cas immunity: adaptation, crRNA biogenesis, and interference. The ecology and regulation of CRISPR-Cas in the context of phage infection, the roles of these systems beyond immunity, and the open questions that propel the field forward are also discussed.
Topics: Adaptive Immunity; Bacteria; Bacteriophages; Biology; CRISPR-Cas Systems; Gene Expression Regulation, Bacterial; Models, Genetic; Signal Transduction
PubMed: 29522745
DOI: 10.1016/j.cell.2017.11.032 -
Frontiers in Immunology 2022Innate immunity is the first defense system against invading pathogens. Toll-like receptors (TLRs) are well-defined pattern recognition receptors responsible for... (Review)
Review
Innate immunity is the first defense system against invading pathogens. Toll-like receptors (TLRs) are well-defined pattern recognition receptors responsible for pathogen recognition and induction of innate immune responses. Since their discovery, TLRs have revolutionized the field of immunology by filling the gap between the initial recognition of pathogens by innate immune cells and the activation of the adaptive immune response. TLRs critically link innate immunity to adaptive immunity by regulating the activation of antigen-presenting cells and key cytokines. Furthermore, recent studies also have shown that TLR signaling can directly regulate the T cell activation, growth, differentiation, development, and function under diverse physiological conditions. This review provides an overview of TLR signaling pathways and their regulators and discusses how TLR signaling, directly and indirectly, regulates cell-mediated immunity. In addition, we also discuss how TLR signaling is critically important in the host's defense against infectious diseases, autoimmune diseases, and cancer.
Topics: Adaptive Immunity; Immunity, Cellular; Immunity, Innate; Signal Transduction; Toll-Like Receptors
PubMed: 35309296
DOI: 10.3389/fimmu.2022.812774 -
Cell Host & Microbe May 2011Immune responses in vertebrates are classically divided into innate and adaptive, with only the latter being able to build up immunological memory. However, although... (Review)
Review
Immune responses in vertebrates are classically divided into innate and adaptive, with only the latter being able to build up immunological memory. However, although lacking adaptive immune responses, plants and invertebrates are protected against reinfection with pathogens, and invertebrates even display transplant rejection. In mammals, past "forgotten" studies demonstrate cross-protection between infections independently of T and B cells, and more recently memory properties for NK cells and macrophages, prototypical cells of innate immunity, have been described. We now posit that mammalian innate immunity also exhibits an immunological memory of past insults, for which we propose the term "trained immunity." Understanding trained immunity will revolutionize our view of host defense and immunological memory, and could lead to defining a new class of vaccines and immunotherapies.
Topics: Adaptive Immunity; Animals; Immunity, Innate; Immunologic Memory; Invertebrates; Plants; Vertebrates
PubMed: 21575907
DOI: 10.1016/j.chom.2011.04.006 -
Frontiers in Immunology 2022Iron is a critical element for living cells in terrestrial life. Although iron metabolism is strictly controlled in the body, disturbance of iron homeostasis under... (Review)
Review
Iron is a critical element for living cells in terrestrial life. Although iron metabolism is strictly controlled in the body, disturbance of iron homeostasis under certain type of condition leads to innate and adaptive immune response. In innate immunity, iron regulates macrophage polarizations, neutrophils recruitment, and NK cells activity. In adaptive immunity, iron had an effect on the activation and differentiation of Th1, Th2, and Th17 and CTL, and antibody response in B cells. In this review, we focused on iron and immune regulation and listed the specific role of iron in macrophage polarization, T-cell activation, and B-cells antibody response. In addition, correlations between iron and several diseases such as cancer and aging degenerative diseases and some therapeutic strategies targeting those diseases are also discussed.
Topics: Adaptive Immunity; Immunity, Innate; Iron; Lymphocyte Activation; Macrophage Activation
PubMed: 35401569
DOI: 10.3389/fimmu.2022.816282 -
Cell Host & Microbe Jan 2019Immunological memory is an important evolutionary trait that improves host survival upon reinfection. Memory is a characteristic recognized within both the innate and... (Review)
Review
Immunological memory is an important evolutionary trait that improves host survival upon reinfection. Memory is a characteristic recognized within both the innate and adaptive arms of the immune system. Although the mechanisms and properties through which innate and adaptive immune memory are induced are distinct, they collude to improve host defense to pathogens. Here, we propose that innate immune memory, or "trained immunity," is a primitive form of adaptation in host defense, resulting from chromatin structure rearrangement, which provides an increased but non-specific response to reinfection. In contrast, adaptive immune memory is more advanced, with increased magnitude of response mediated through epigenetic changes, as well as specificity mediated by gene recombination. An integrative model of immune memory is important for broad understanding of host defense, and for identifying the most effective approaches to modulate it for the benefit of patients with infections and immune-mediated diseases.
Topics: Adaptive Immunity; Animals; Biological Evolution; Epigenesis, Genetic; Humans; Immunity, Innate; Immunologic Memory; Infections; Lymphocytes; Recombination, Genetic
PubMed: 30629914
DOI: 10.1016/j.chom.2018.12.006 -
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