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Trained Immunity
Trained immunity is a long-term functional modification of cells in the innate immune system which leads to an altered response to a second unrelated challenge. For example, the BCG vaccine leads to a reduction in childhood mortality caused by unrelated infectious agents. The term "innate immune memory" is sometimes used as a synonym for the term ''trained immunity'' which was first coined by Mihai Netea in 2011. The term "trained immunity" is relatively new – immunological memory has previously been considered only as a part of adaptive immunity – and refers only to changes in innate immune memory of vertebrates. This type of immunity is thought to be largely mediated by epigenetic modifications. The changes to the innate immune response may last up to several months, in contrast to the classical immunological memory (which may last up to a lifetime), and is usually unspecific because there is no production of specific antibodies/receptors. Trained immunity has been sugg ...
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Innate Immune System
The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the dominant immune system response found in plants, fungi, insects, and primitive multicellular organisms (see Beyond vertebrates).. The major functions of the innate immune system are to: * recruit immune cells to infection sites by producing chemical factors, including chemical mediators called cytokines * activate the complement cascade to identify bacteria, activate cells, and promote clearance of antibody complexes or dead cells * identify and remove foreign substances present in organs, tissues, blood and lymph, by specialized white blood cells * activate the adaptive immune system through antigen presentation * act as a physical and chemical barrier to infectious agents; via physical measures such as skin and chemical measures such a ...
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Innate Lymphoid Cell
Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells, derived from common lymphoid progenitors (CLPs). In response to pathogenic tissue damage, ILCs contribute to immunity via the secretion of signalling molecules, and the regulation of both innate and adaptive immune cells. ILCs are primarily tissue resident cells, found in both lymphoid (immune associated), and non- lymphoid tissues, and rarely in the blood. They are particularly abundant at mucosal surfaces, playing a key role in mucosal immunity and homeostasis. Characteristics allowing their differentiation from other immune cells include the regular lymphoid morphology, absence of rearranged antigen receptors found on T cells and B cells (due to the lack of the RAG gene), and phenotypic markers usually present on myeloid or dendritic cells. Based on the difference in developmental pathways, phenotype, and signalling molecules produced, in 2013, ILCs were divided into three groups: ...
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Oxidative Phosphorylation
Oxidative phosphorylation (UK , US ) or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing chemical energy in order to produce adenosine triphosphate (ATP). In eukaryotes, this takes place inside mitochondria. Almost all aerobic organisms carry out oxidative phosphorylation. This pathway is so pervasive because it releases more energy than alternative fermentation processes such as anaerobic glycolysis. The energy stored in the chemical bonds of glucose is released by the cell in the citric acid cycle producing carbon dioxide, and the energetic electron donors NADH and FADH. Oxidative phosphorylation uses these molecules and O2 to produce ATP, which is used throughout the cell whenever energy is needed. During oxidative phosphorylation, electrons are transferred from the electron donors to a series of electron acceptors in a series of redox reactions ending in oxygen, who ...
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Citric Acid Cycle
The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. The Krebs cycle is used by organisms that respire (as opposed to organisms that ferment) to generate energy, either by anaerobic respiration or aerobic respiration. In addition, the cycle provides precursors of certain amino acids, as well as the reducing agent NADH, that are used in numerous other reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest components of metabolism and may have originated abiogenically. Even though it is branded as a 'cycle', it is not necessary for metabolites to follow only one specific route; at least three alternative segments of the citric acid cycle have been recognized. The name of this metabolic pathway is derived from the citric acid (a tricarboxy ...
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Hypoxia-inducible Factor
Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or hypoxia. They are only present in parahoxozoan animals. Discovery The HIF transcriptional complex was discovered in 1995 by Gregg L. Semenza and postdoctoral fellow Guang Wang. In 2016, William Kaelin Jr., Peter J. Ratcliffe and Gregg L. Semenza were presented the Lasker Award for their work in elucidating the role of HIF-1 in oxygen sensing and its role in surviving low oxygen conditions. In 2019, the same three individuals were jointly awarded the Nobel Prize in Physiology or Medicine for their work in elucidating how HIF senses and adapts cellular response to oxygen availability. Structure Most, if not all, oxygen-breathing species express the highly conserved transcriptional complex HIF-1, which is a heterodimer composed of an alpha and a beta subunit, the latter being a constitutively-expressed aryl hydrocarbon receptor nucle ...
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PI3K/AKT/mTOR Pathway
The PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle. Therefore, it is directly related to cellular quiescence, proliferation, cancer, and longevity. PI3K activation phosphorylates and activates AKT, localizing it in the plasma membrane. AKT can have a number of downstream effects such as activating CREB, inhibiting p27, localizing FOXO in the cytoplasm, activating PtdIns-3ps, and activating mTOR which can affect transcription of p70 or 4EBP1. There are many known factors that enhance the PI3K/AKT pathway including EGF, shh, IGF-1, insulin, and CaM. Both leptin and insulin recruit PI3K signalling for metabolic regulation. The pathway is antagonized by various factors including PTEN, GSK3B, and HB9. In many cancers, this pathway is overactive, thus reducing apoptosis and allowing proliferation. This pathway is necessary, however, to promote growth and proliferation over differentiation of adult stem cells, neural stem cells sp ...
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Macrophage Polarization
Macrophage polarization is a process by which macrophages adopt different functional programs in response to the signals from their microenvironment. This ability is connected to their multiple roles in the organism: they are powerful effector cells of the innate immune system, but also important in removal of cellular debris, embryonic development and tissue repair. By simplified classification, macrophage phenotype has been divided into 2 groups: M1 (classically activated macrophages) and M2 (alternatively activated macrophages). This broad classification was based on ''in vitro'' studies, in which cultured macrophages were treated with molecules that stimulated their phenotype switching to a particular state. In addition to chemical stimulation, it has been shown that the stiffness of the underlying substrate a macrophage is grown on can direct polarization state, functional roles and migration mode. A continuum of M1-M2 polarization may arise even in the absence of polarizing cyt ...
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Glycolysis
Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH). Glycolysis is a sequence of ten reactions catalyzed by enzymes. Glycolysis is a metabolic pathway that does not require oxygen (In anaerobic conditions pyruvate is converted to lactic acid). The wide occurrence of glycolysis in other species indicates that it is an ancient metabolic pathway. Indeed, the reactions that make up glycolysis and its parallel pathway, the pentose phosphate pathway, occur in the oxygen-free conditions of the Archean oceans, also in the absence of enzymes, catalyzed by metal. In most organisms, glycolysis occurs in the liquid part of cells, the cytosol. The most common type of glycolysis is the ''Embden–Meyerhof–Parnas (EMP) pathway'', which was discovered by Gustav Embden, Otto Meyerhof, and Jakub Karol ...
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Interferon Gamma
Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock as a product of human leukocytes stimulated with phytohemagglutinin, and by others as a product of antigen-stimulated lymphocytes. It was also shown to be produced in human lymphocytes. or tuberculin-sensitized mouse peritoneal lymphocytes challenged with Mantoux test (PPD); the resulting supernatants were shown to inhibit growth of vesicular stomatitis virus. Those reports also contained the basic observation underlying the now widely employed IFN-γ release assay used to test for tuberculosis. In humans, the IFN-γ protein is encoded by the ''IFNG'' gene. Through cell signaling, IFN-γ plays a role in regulating the immune response of its target cell. A key signaling pathway that is activated by type II IFN is the JAK-STAT signal ...
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Dendritic Cell
Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and the adaptive immune systems. Dendritic cells are present in those tissues that are in contact with the external environment, such as the skin (where there is a specialized dendritic cell type called the Langerhans cell) and the inner lining of the nose, lungs, stomach and intestines. They can also be found in an immature state in the blood. Once activated, they migrate to the lymph nodes where they interact with T cells and B cells to initiate and shape the adaptive immune response. At certain development stages they grow branched projections, the ''dendrites'' that give the cell its name (δένδρον or déndron being Greek for 'tree'). While similar in appearance, these are structures ...
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Progenitor Cell
A progenitor cell is a Cell (biology), biological cell that can Cellular differentiation, differentiate into a specific cell type. Stem cells and progenitor cells have this ability in common. However, stem cells are less specified than progenitor cells. Progenitor cells can only differentiate into their "target" cell type. The most important difference between stem cells and progenitor cells is that stem cells can replicate indefinitely, whereas progenitor cells can divide only a limited number of times. Controversy about the exact definition remains and the concept is still evolving. The terms "progenitor cell" and "stem cell" are sometimes equated. Properties Most progenitors are identified as Oligopotency, oligopotent. In this point of view, they can compare to adult stem cells, but progenitors are said to be in a further stage of cell differentiation. They are in the "center" between stem cells and fully differentiated cells. The kind of potency they have depends on the type ...
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Tuberculosis
Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in which case it is known as latent tuberculosis. Around 10% of latent infections progress to active disease which, if left untreated, kill about half of those affected. Typical symptoms of active TB are chronic cough with blood-containing mucus, fever, night sweats, and weight loss. It was historically referred to as consumption due to the weight loss associated with the disease. Infection of other organs can cause a wide range of symptoms. Tuberculosis is spread from one person to the next through the air when people who have active TB in their lungs cough, spit, speak, or sneeze. People with Latent TB do not spread the disease. Active infection occurs more often in people with HIV/AIDS and in those who smoke. Diagnosis of active TB is ...
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