The Experts below are selected from a list of 99 Experts worldwide ranked by ideXlab platform
Francisco Ramirez - One of the best experts on this subject based on the ideXlab platform.
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Phenotypic analysis of peripheral CD4+ CD8+ T cells in the rat
Immunology, 2000Co-Authors: E. Kenny, Don Mason, Ana Pombo, Francisco RamirezAbstract:Among peripheral T cells, the expression of CD4 and CD8 is almost mutually exclusive. However, here we show, using flow cytometric analysis, that ex vivo approximately 6% of rat T cells stained for both CD4 and CD8. These double positive cells were also detected by confocal microscopy. Only around 50% of double positive cells expressed the CD8beta chain, the remaining cells expressed the CD8alpha chain alone. Double positive cells were blast-like with a phenotype, distinct from that of either CD4 or CD8 single positive cells, suggestive of an activated state. Previous reports of double positive T cells have also suggested that coexpression of CD4 and CD8 is linked to the activation state of the cell. There was an indication that priming animals with a Hapten-Carrier Complex increased the ratio of CD8alphaalpha : alphabeta expressing double positive T cells, although we did not detect an increase in the frequency of double positive T cells following priming. We also show that the frequency of double positive cells was reduced following thymectomy and with age. In conclusion, these studies show that peripheral T cells expressing both CD4 and CD8 can be detected in the rat and that they are phenotypically distinct from CD4 and CD8 single positive T cells.
Shicui Zhang - One of the best experts on this subject based on the ideXlab platform.
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Maternal transfer and protective role of antibodies in zebrafish Danio rerio.
Molecular immunology, 2012Co-Authors: Hongmiao Wang, Jianzhong Shao, Shicui ZhangAbstract:Maternal transfer of antibodies from mother to eggs has been reported in various species of fishes, and these antibodies have been proposed to play immune roles in developing embryos and larvae. However, firm evidence supporting this remains lacking. In this study, we clearly demonstrated that immunization of female zebrafish with the Hapten-Carrier Complex, trinitrophenylated bovine serum albumin (TNP-BSA), induced a significant increase in anti-TNP antibody production in the mothers, which in turn induced a marked increase in anti-TNP antibody level in their eggs. Microinjection of anti-zebrafish IgM antibody into early embryos (to neutralize endogenous antibody action) resulted in a remarkable decrease in the resistance of recipient embryos to pathogenic Aeromonas hydrophila, whereas injection of BSA or anti-β-actin monoclonal antibody into the same stage embryos had little effect on their resistance to the pathogen. Moreover, the content of endogenous antibodies in eggs was clearly correlated with their antibacterial activity against A. hydrophila. This is the first report showing that maternally transferred antibodies in fish can protect early embyros/larvae from the attack of pathogens like A. hydrophila.
E. Kenny - One of the best experts on this subject based on the ideXlab platform.
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Phenotypic analysis of peripheral CD4+ CD8+ T cells in the rat
Immunology, 2000Co-Authors: E. Kenny, Don Mason, Ana Pombo, Francisco RamirezAbstract:Among peripheral T cells, the expression of CD4 and CD8 is almost mutually exclusive. However, here we show, using flow cytometric analysis, that ex vivo approximately 6% of rat T cells stained for both CD4 and CD8. These double positive cells were also detected by confocal microscopy. Only around 50% of double positive cells expressed the CD8beta chain, the remaining cells expressed the CD8alpha chain alone. Double positive cells were blast-like with a phenotype, distinct from that of either CD4 or CD8 single positive cells, suggestive of an activated state. Previous reports of double positive T cells have also suggested that coexpression of CD4 and CD8 is linked to the activation state of the cell. There was an indication that priming animals with a Hapten-Carrier Complex increased the ratio of CD8alphaalpha : alphabeta expressing double positive T cells, although we did not detect an increase in the frequency of double positive T cells following priming. We also show that the frequency of double positive cells was reduced following thymectomy and with age. In conclusion, these studies show that peripheral T cells expressing both CD4 and CD8 can be detected in the rat and that they are phenotypically distinct from CD4 and CD8 single positive T cells.
Werner J. Pichler - One of the best experts on this subject based on the ideXlab platform.
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The p-i Concept: Pharmacological Interaction of Drugs With Immune Receptors
2016Co-Authors: Werner J. PichlerAbstract:Abstract: The immune response in drug hypersensitivity is normally explained by the Hapten hypothesis. It postulates that drugs with a molecular weight of less than 1000D are too small to cause an immune response per se. However, if a chemically reactive drug or drug metabolite binds covalently to a protein and thus forms a so-called Hapten-Carrier Complex, this modified protein can induce an immune response. This concept has recently been supplemented by the p-i concept (or pharmacological interaction with immune receptors), which postulates that some drugs that lack Hapten characteristics can bind directly and reversibly (noncovalently) to immune receptors and thereby stimulate the cells. For example, a certain drug may bind to a particular T-cell receptor, and this binding suffices to stimulate the T cell to secrete cytokines, to proliferate, and to exert cytotoxicity. The p-i concept has major implications for our understanding of drug interaction with the specific immune system and for drug hypersensi
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The p-i Concept: Pharmacological Interaction of Drugs With Immune Receptors
World Allergy Organization Journal, 2008Co-Authors: Werner J. PichlerAbstract:The immune response in drug hypersensitivity is normally explained by the Hapten hypothesis. It postulates that drugs with a molecular weight of less than 1000 D are too small to cause an immune response per se. However, if a chemically reactive drug or drug metabolite binds covalently to a protein and thus forms a so-called Hapten-Carrier Complex, this modified protein can induce an immune response. This concept has recently been supplemented by the p-i concept (or pharmacological interaction with immune receptors), which postulates that some drugs that lack Hapten characteristics can bind directly and reversibly (noncovalently) to immune receptors and thereby stimulate the cells. For example, a certain drug may bind to a particular T-cell receptor, and this binding suffices to stimulate the T cell to secrete cytokines, to proliferate, and to exert cytotoxicity. The p-i concept has major implications for our understanding of drug interaction with the specific immune system and for drug hypersensitivity reactions. It is based on extensive investigations of T-cell clones reacting with the drug and recently of hybridoma cells transfected with the drug-specific T-cell receptor for antigen (TCR). It is a highly specific interaction dependent on the expression of a TCR into which the drug can bind with sufficient affinity to cause signaling. Small modification of the drug structure may already abrogate reactivity. Stimulation of T cells occurs within minutes as revealed by rapid Ca^++ influx after drug addition to drug-specific T-cell clones or hybridoma cells, thus, before metabolism and processing can occur. As the immune system can only react in an immunologic way, the symptoms arising after drug stimulation of immune receptors imitate an immune response after recognition of a peptide antigen, although it is actually a pharmacological stimulation of some T cells via their TCRs. Clinically, the p-i concept could explain the sometimes rapid appearance of symptoms without previous sensitizations and the sometimes chaotic immune reaction of drug hypersensitivity with participation of different immune mechanisms while normal immune reactions to antigens are highly coordinated. Nevertheless, because the reactions lead to expansion of drug-reactive cells, many features such as skin test reactivity and stronger reactivity upon reexposure are identical to real immune reactions.
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Pharmacological Interaction of Drugs with Immune Receptors: The p-i Concept
Allergology international : official journal of the Japanese Society of Allergology, 2006Co-Authors: Werner J. Pichler, Andreas Beeler, Monika Keller, Marianne Lerch, Sinforiano Posadas, Daphne Anne Schmid, Zoi Spanou, Anna Zawodniak, Basil O. GerberAbstract:Drug-induced hypersensitivity reactions have been explained by the Hapten concept, according to which a small chemical compound is too small to be recognized by the immune system. Only after covalently binding to an endogenous protein the immune system reacts to this so called Hapten-Carrier Complex, as the larger molecule (protein) is modified, and thus immunogenic for B and T cells. Consequently, a B and T cell immune response might develop to the drug with very heterogeneous clinical manifestations. In recent years, however, evidence has become stronger that not all drugs need to bind covalently to the MHC-peptide Complex in order to trigger an immune response. Rather, some drugs may bind directly and reversibly to immune receptors like the major histocompatibility Complex (MHC) or the T cell receptor (TCR), thereby stimulating the cells similar to a pharmacological activation of other receptors. This concept has been termed pharmacological interaction with immune receptors the (p-i) concept. While the exact mechanism is still a matter of debate, non-covalent drug presentation clearly leads to the activation of drug-specific T cells as documented for various drugs (lidocaine, sulfamethoxazole (SMX), lamotrigine, carbamazepine, p-phenylendiamine, etc.). In some patients with drug hypersensitivity, such a response may occur within hours even upon the first exposure to the drug. Thus, the reaction to the drug may not be due to a classical, primary response, but rather be mediated by stimulating existing, pre-activated, peptide-specific T cells that are cross specific for the drug. In this way, certain drugs may circumvent the checkpoints for immune activation imposed by the classical antigen processing and presentation mechanisms, which may help to explain the peculiar nature of many drug hypersensitivity reactions.
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Pharmacological interaction of drugs with immune receptors: The p-i concept. Allergol. Int
2006Co-Authors: Werner J. Pichler, Andreas Beeler, Monika Keller, Marianne Lerch, Sinforiano Posadas, Zoi Spanou, Anna Zawodniak, Daphn Schmid, Basil GerberAbstract:Drug-induced hypersensitivity reactions have been explained by the Hapten concept, according to which a small chemical compound is too small to be recognized by the immune system. Only after covalently binding to an endogenous protein the immune system reacts to this so called Hapten-Carrier Complex, as the larger mole-cule (protein) is modified, and thus immunogenic for B and T cells. Consequently, a B and T cell immune re-sponse might develop to the drug with very heterogeneous clinical manifestations? In recent years, however, evidence has become stronger that not all drugs need to bind covalently to the MHC-peptide Complex in order to trigger an immune response. Rather, some drugs may bind directly and reversibly to immune receptors like the major histocompatibility Complex (MHC) or the T cell receptor (TCR), thereby stimulating the cells similar to a pharmacological activation of other receptors. This concept has been termed pharmacological interaction with immune receptors the (p-i) concept. While the exact mechanism is still a mat-ter of debate, non-covalent drug presentation clearly leads to the activation of drug-specific T cells as docu-mented for various drugs ( lidocaine, sulfamethoxazole ( SMX) , lamotrigine, carbamazepine, p-phenylendiamine, etc.).In some patients with drug hypersensitivity, such a response may occur within hours even upon the first exposure to the drug. Thus, the reaction to the drug may not be due to a classical, primary response, but rather be mediated by stimulating existing, pre-activated, peptide-specific T cells that are cross specific for the drug. In this way, certain drugs may circumvent the checkpoints for immune activation imposed by the classical antigen processing and presentation mechanisms, which may help to explain the peculiar na-ture of many drug hypersensitivity reactions
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The p-i Concept: Pharmacological Interaction of Drugs With Immune Receptors
Elsevier, 1Co-Authors: Werner J. PichlerAbstract:The immune response in drug hypersensitivity is normally explained by the Hapten hypothesis. It postulates that drugs with a molecular weight of less than 1000 D are too small to cause an immune response per se. However, if a chemically reactive drug or drug metabolite binds covalently to a protein and thus forms a so-called Hapten-Carrier Complex, this modified protein can induce an immune response. This concept has recently been supplemented by the p-i concept (or pharmacological interaction with immune receptors), which postulates that some drugs that lack Hapten characteristics can bind directly and reversibly (noncovalently) to immune receptors and thereby stimulate the cells. For example, a certain drug may bind to a particular T-cell receptor, and this binding suffices to stimulate the T cell to secrete cytokines, to proliferate, and to exert cytotoxicity. The p-i concept has major implications for our understanding of drug interaction with the specific immune system and for drug hypersensitivity reactions. It is based on extensive investigations of T-cell clones reacting with the drug and recently of hybridoma cells transfected with the drug-specific T-cell receptor for antigen (TCR). It is a highly specific interaction dependent on the expression of a TCR into which the drug can bind with sufficient affinity to cause signaling. Small modification of the drug structure may already abrogate reactivity. Stimulation of T cells occurs within minutes as revealed by rapid Ca++ influx after drug addition to drug-specific T-cell clones or hybridoma cells, thus, before metabolism and processing can occur. As the immune system can only react in an immunologic way, the symptoms arising after drug stimulation of immune receptors imitate an immune response after recognition of a peptide antigen, although it is actually a pharmacological stimulation of some T cells via their TCRs. Clinically, the p-i concept could explain the sometimes rapid appearance of symptoms without previous sensitizations and the sometimes chaotic immune reaction of drug hypersensitivity with participation of different immune mechanisms while normal immune reactions to antigens are highly coordinated. Nevertheless, because the reactions lead to expansion of drug-reactive cells, many features such as skin test reactivity and stronger reactivity upon reexposure are identical to real immune reactions. Keywords: p-i concept, drug hypersensitivity, Hapten, proHapten, T-cell receptor, T cell
Don Mason - One of the best experts on this subject based on the ideXlab platform.
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Phenotypic analysis of peripheral CD4+ CD8+ T cells in the rat
Immunology, 2000Co-Authors: E. Kenny, Don Mason, Ana Pombo, Francisco RamirezAbstract:Among peripheral T cells, the expression of CD4 and CD8 is almost mutually exclusive. However, here we show, using flow cytometric analysis, that ex vivo approximately 6% of rat T cells stained for both CD4 and CD8. These double positive cells were also detected by confocal microscopy. Only around 50% of double positive cells expressed the CD8beta chain, the remaining cells expressed the CD8alpha chain alone. Double positive cells were blast-like with a phenotype, distinct from that of either CD4 or CD8 single positive cells, suggestive of an activated state. Previous reports of double positive T cells have also suggested that coexpression of CD4 and CD8 is linked to the activation state of the cell. There was an indication that priming animals with a Hapten-Carrier Complex increased the ratio of CD8alphaalpha : alphabeta expressing double positive T cells, although we did not detect an increase in the frequency of double positive T cells following priming. We also show that the frequency of double positive cells was reduced following thymectomy and with age. In conclusion, these studies show that peripheral T cells expressing both CD4 and CD8 can be detected in the rat and that they are phenotypically distinct from CD4 and CD8 single positive T cells.
