Non-peptidic Antigen
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Non-peptidic Antigen
Non-peptidic antigens are low-molecular-weight compounds that stimulate human Vγ9/Vδ2 T cells. The most potent activator for Vγ9/Vδ2 T cells is (''E'')-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), a natural intermediate of the non-mevalonate pathway of isopentenyl pyrophosphate (IPP) biosynthesis. HMB-PP is an essential metabolite in most pathogenic bacteria including ''Mycobacterium tuberculosis'' as well as in malaria parasites, but is absent from the human host. IPP itself is structurally closely related to HMB-PP and ubiquitously present in all living cells (i.e., also in human cells), yet its potency ''in vitro'' is 10,000-fold reduced; whether IPP represents a physiological 'danger' signal of stressed or transformed cells is still unclear. Of pharmacological interest and with bioactivities comparable to that of IPP are synthetic aminobisphosphonates such as zoledronate (Zometa) that are widely used to treat osteoporosis and bone metastases, and act as Vγ9/VΠ...
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Vg9/Vd2 T Cells
Gamma delta T cells (γδ T cells) are T cells that have a γδ T-cell receptor (TCR) on their surface. Most T cells are αβ (alpha beta) T cells with TCR composed of two glycoprotein chains called α (alpha) and β (beta) TCR chains. In contrast, γδ T cells have a TCR that is made up of one γ (gamma) chain and one δ (delta) chain. This group of T cells is usually less common than αβ T cells, but are at their highest abundance in the gut mucosa, within a population of lymphocytes known as intraepithelial lymphocytes (IELs). The antigenic molecules that activate gamma delta T cells are still largely unknown. However, γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes, although some recognize MHC class Ib molecules. γδ T cells are believed to have a prominent role in recognition of lipid antigens. They are of an invariant nature and may be triggered by alarm signals, su ...
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HMB-PP
(''E'')-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP or HMB-PP) is an intermediate of the MEP pathway (non-mevalonate pathway) of isoprenoid biosynthesis. The enzyme HMB-PP synthase (GcpE, IspG) catalyzes the conversion of 2-''C''-methyl-D-erythritol 2,4-cyclodiphosphate (MEcPP) into HMB-PP. HMB-PP is then converted further to isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) by HMB-PP reductase (LytB, IspH). HMB-PP is an essential metabolite in most pathogenic bacteria including ''Mycobacterium tuberculosis'' as well as in malaria parasites, but is absent from the human host. HMB-PP is the physiological activator ("phosphoantigen Non-peptidic antigens are low-molecular-weight compounds that stimulate human Vg9/Vd2 T cells, Vγ9/Vδ2 T cells. The most potent activator for Vγ9/Vδ2 T cells is (''E'')-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), a natural intermediate ...") for human Vγ9/Vδ2 T cells, the major γδ T cell population in p ...
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Non-mevalonate Pathway
The non-mevalonate pathway—also appearing as the mevalonate-independent pathway and the 2-''C''-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate (MEP/DOXP) pathway—is an alternative metabolic pathway for the biosynthesis of the isoprenoid precursors isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). The currently preferred name for this pathway is the MEP pathway, since MEP is the first committed metabolite on the route to IPP. Isoprenoid precursor biosynthesis The classical mevalonate pathway (MVA pathway or HMG-CoA reductase pathway) is a metabolic pathway for the biosynthesis of isoprenoid precursors: IPP and DMAPP. The MVA pathway is present in most eukaryotes and some bacteria. IPP and DMAPP serve as the basis for the biosynthesis of isoprenoid (terpenoid) molecules used in processes as diverse as protein prenylation, cell membrane maintenance, the synthesis of hormones, protein anchoring and ''N''-glycosylation in all three domains ...
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Isopentenyl Pyrophosphate
Isopentenyl pyrophosphate (IPP, isopentenyl diphosphate, or IDP) is an isoprenoid precursor. IPP is an intermediate in the classical, HMG-CoA reductase pathway (commonly called the mevalonate pathway) and in the ''non-mevalonate'' MEP pathway of isoprenoid precursor biosynthesis. Isoprenoid precursors such as IPP, and its isomer DMAPP, are used by organisms in the biosynthesis of terpenes and terpenoids. Biosynthesis IPP is formed from acetyl-CoA via the mevalonate pathway (the "upstream" part), and then is isomerized to dimethylallyl pyrophosphate by the enzyme isopentenyl pyrophosphate isomerase. IPP can be synthesised via an alternative non-mevalonate pathway of isoprenoid precursor biosynthesis, the MEP pathway, where it is formed from (''E'')-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) by the enzyme HMB-PP reductase (LytB, IspH). The MEP pathway is present in many bacteria, apicomplexan protozoa such as malaria parasites, and in the plastids of higher plant ...
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Mycobacterium Tuberculosis
''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' has an unusual, waxy coating on its cell surface primarily due to the presence of mycolic acid. This coating makes the cells impervious to Gram staining, and as a result, ''M. tuberculosis'' can appear weakly Gram-positive. Acid-fastness, Acid-fast stains such as Ziehl–Neelsen stain, Ziehl–Neelsen, or Fluorescence, fluorescent stains such as Auramine O, auramine are used instead to identify ''M. tuberculosis'' with a microscope. The physiology of ''M. tuberculosis'' is highly aerobic organism, aerobic and requires high levels of oxygen. Primarily a pathogen of the mammalian respiratory system, it infects the lungs. The most frequently used diagnostic methods for tuberculosis are the Mantoux test, tuberculin skin test, Acid-Fast Stain, acid-fast stain, Microbiological cultu ...
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Malaria
Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. Symptoms usually begin ten to fifteen days after being bitten by an infected mosquito. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria. Malaria is caused by single-celled microorganisms of the ''Plasmodium'' group. It is spread exclusively through bites of infected ''Anopheles'' mosquitoes. The mosquito bite introduces the parasites from the mosquito's saliva into a person's blood. The parasites travel to the liver where they mature and reproduce. Five species of ''Plasmodium'' can infect and be spread by h ...
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Bisphosphonates
Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they have two phosphonate () groups. They are thus also called diphosphonates ('' bis-'' or '' di-'' + ''phosphonate''). Evidence shows that they reduce the risk of fracture in post-menopausal women with osteoporosis. Bone tissue undergoes constant remodeling and is kept in balance (homeostasis) by osteoblasts creating bone and osteoclasts destroying bone. Bisphosphonates inhibit the digestion of bone by encouraging osteoclasts to undergo apoptosis, or cell death, thereby slowing bone loss. The uses of bisphosphonates include the prevention and treatment of osteoporosis, Paget's disease of bone, bone metastasis (with or without hypercalcemia), multiple myeloma, primary hyperparathyroidism, osteogenesis imperfecta, fibrous dysplasia, and other ...
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Zoledronate
Zoledronic acid, also known as zoledronate and sold under the brand name Zometa by Novartis among others, is a medication used to treat a number of bone diseases. These include osteoporosis, high blood calcium due to cancer, bone breakdown due to cancer, Paget's disease of bone and Duchenne muscular dystrophy (DMD). It is given by injection into a vein. Common side effects include fever, joint pain, high blood pressure, diarrhea, and feeling tired. Serious side effects may include kidney problems, low blood calcium, and osteonecrosis of the jaw. Use during pregnancy may result in harm to the baby. It is in the bisphosphonate family of medications. It works by blocking the activity of osteoclast cells and thus decreases the breakdown of bone. Zoledronic acid was patented in 1986 and approved for medical use in the United States in 2001. It is on the World Health Organization's List of Essential Medicines. Medical uses Bone complications of cancer Zoledronic acid is used t ...
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