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Annales D'immunologie 1976The evidence for the one non-specific signal hypothesis stating that the B lymphocytes are activated by non-clonally distributed receptors which are not the Ig... (Review)
Review
The evidence for the one non-specific signal hypothesis stating that the B lymphocytes are activated by non-clonally distributed receptors which are not the Ig receptors, have been summarized. Even though protein A is a polyclonal B cell activator, it does not exert its effect by interacting with the Fc part of Ig receptors. One consequence of the one non-specific signal concept is that thymus-dependent antigens cannot activate or tolerize B cells. It was shown that B cells from animals tolerant to a thymus-dependent protein antigen could be activated by polyclonal B cell activators to produce antibodies against the tolerogen. Experimentally induced tolerance did not differ from tolerance to self antigens, since LPS and PPD induced autoantibodies capable of lysing autologous red cells and isotope labelled autologous and syngeneic spleen cells. Thus, B cells cannot discriminate self from nonself whereas T cells have been shown to possess this ability.
Topics: Animals; Antibody Formation; Autoantibodies; B-Lymphocytes; Bacterial Proteins; Binding Sites, Antibody; Cell Differentiation; Clone Cells; Epitopes; Genes; Immune Tolerance; Immunity, Maternally-Acquired; Mice; Receptors, Antigen, B-Cell; Staphylococcus aureus; T-Lymphocytes
PubMed: 60905
DOI: No ID Found -
Poultry Science Nov 2011The purpose of this study was to analyze the effect of auditory enrichment (by means of classical music) or physical enrichment (by means of hanging colored string...
Effects of auditory and physical enrichment on 3 measurements of fear and stress (tonic immobility duration, heterophil to lymphocyte ratio, and fluctuating asymmetry) in several breeds of layer chicks.
The purpose of this study was to analyze the effect of auditory enrichment (by means of classical music) or physical enrichment (by means of hanging colored string bunches and barley grains on the floor) on tonic immobility duration, heterophil to lymphocyte ratio, and fluctuating asymmetry (FA) in chicks of several layer breeds. In experiment 1, 192 chicks from 8 Spanish breeds and 1 White Leghorn population were reared in cages with or without music auditory enrichment until 8 wk of age. The effect of music auditory enrichment was significant for heterophil to lymphocyte ratio (P < 0.05). The ratios were higher in chicks reared without music than in those reared with music, suggesting that auditory enrichment from classical music reduces stress in chicks. There were significant differences in morphological trait measurements (relative asymmetry of wing length, leg width, and combined asymmetry; P < 0.05), being greater in chicks reared without music. This result suggests that FA is a good indicator for stress level in chicks, given that it follows the same trend as that found for heterophil to lymphocyte ratio. There was a significant treatment by breed interaction (P < 0.05) for tonic immobility duration, indicating no consistent effect by auditory enrichment on tonic immobility duration across breeds. In experiment 2, 180 chicks from 3 Spanish breeds were housed in pens with or without physical enrichment (colored plastic string bunches and barley grains on the floor) until 6 wk of age. The effect of physical enrichment on tonic immobility duration, heterophil to lymphocyte ratio, and FA was not significant, indicating no effect on fear and stress in layer chicks. In conclusion, auditory enrichment by means of classical music is a reliable method for reducing stress levels in several breeds of layer chicks. However, music auditory enrichment was not effective in reducing fearfulness in any of the layer breeds. Physical enrichment by means of colored plastic string bunches and floor barley grains does not appear to be an effective method for reducing stress and fear in layer chicks.
Topics: Animal Husbandry; Animals; Chickens; Fear; Immobility Response, Tonic; Lymphocytes; Sound; Stress, Physiological
PubMed: 22010229
DOI: 10.3382/ps.2011-01595 -
Biophysical Journal Sep 2020Mammalian cells developed two main migration modes. The slow mesenchymatous mode, like crawling of fibroblasts, relies on maturation of adhesion complexes and actin...
Mammalian cells developed two main migration modes. The slow mesenchymatous mode, like crawling of fibroblasts, relies on maturation of adhesion complexes and actin fiber traction, whereas the fast amoeboid mode, observed exclusively for leukocytes and cancer cells, is characterized by weak adhesion, highly dynamic cell shapes, and ubiquitous motility on two-dimensional and in three-dimensional solid matrix. In both cases, interactions with the substrate by adhesion or friction are widely accepted as a prerequisite for mammalian cell motility, which precludes swimming. We show here experimental and computational evidence that leukocytes do swim, and that efficient propulsion is not fueled by waves of cell deformation but by a rearward and inhomogeneous treadmilling of the cell external membrane. Our model consists of a molecular paddling by transmembrane proteins linked to and advected by the actin cortex, whereas freely diffusing transmembrane proteins hinder swimming. Furthermore, continuous paddling is enabled by a combination of external treadmilling and selective recycling by internal vesicular transport of cortex-bound transmembrane proteins. This mechanism explains observations that swimming is five times slower than the retrograde flow of cortex and also that lymphocytes are motile in nonadherent confined environments. Resultantly, the ubiquitous ability of mammalian amoeboid cells to migrate in two dimensions or three dimensions and with or without adhesion can be explained for lymphocytes by a single machinery of heterogeneous membrane treadmilling.
Topics: Actins; Amoeba; Animals; Cell Adhesion; Cell Movement; Lymphocytes; Swimming
PubMed: 32882187
DOI: 10.1016/j.bpj.2020.07.033 -
Brazilian Journal of Medical and... 2023Regular exercise reduces the risk of malignancy and decreases the recurrence of cancer. However, the mechanisms behind this protection remain to be elucidated. Natural...
Twelve-week treadmill endurance training in mice is associated with upregulation of interleukin-15 and natural killer cell activation and increases apoptosis rate in Hepa1-6 cell-derived mouse hepatomas.
Regular exercise reduces the risk of malignancy and decreases the recurrence of cancer. However, the mechanisms behind this protection remain to be elucidated. Natural killer (NK) cells are lymphocytes of the innate immune system, which play essential roles in immune defense and effectively prevent cancer metastasis. Physical exercise can increase the activity of NK cells. Interleukin-15 (IL-15) is the best-studied cytokine activator of NK cells, and it was shown to have many positive functional effects on NK cells to improve antitumor responses. The aim of this study was to clarify the possible important mechanisms behind endurance exercise-induced changes in NK cell function, which may be highly correlated with IL-15. An animal model was used to study IL-15 expression level, tumor volume, cancer cell apoptosis, and NK cell infiltration after treadmill exercise. Although IL-15 was highly expressed in skeletal muscle, treadmill exercise further elevated IL-15 levels in plasma and muscle (P<0.05). In addition, tumor weight and volume of tumor-bearing mice were decreased (P<0.05), and liver tumor cell apoptosis was increased after 12 weeks of treadmill exercise (P<0.05). NK cell infiltration was upregulated in tumors from treadmill exercise mice, and the level of interferon-gamma (IFN-γ) and IL-15 were higher than in sedentary mice (P<0.05). The study indicated that regular endurance training can reduce cancer risk, which was related to increased IL-15 expression, activation of the immune killing effect of NK cells, and promotion of tumor cell apoptosis, which can ultimately control tumor growth.
Topics: Animals; Mice; Apoptosis; Carcinoma, Hepatocellular; Endurance Training; Interleukin-15; Killer Cells, Natural; Liver Neoplasms; Up-Regulation; Physical Conditioning, Animal
PubMed: 37585912
DOI: 10.1590/1414-431X2023e12296 -
Journal of Pharmacological Sciences Feb 2008Lymphocytes possess all the components required to constitute an independent, non-neuronal cholinergic system. These include acetylcholine (ACh); choline... (Review)
Review
Basic and clinical aspects of non-neuronal acetylcholine: expression of an independent, non-neuronal cholinergic system in lymphocytes and its clinical significance in immunotherapy.
Lymphocytes possess all the components required to constitute an independent, non-neuronal cholinergic system. These include acetylcholine (ACh); choline acetyltransferase (ChAT), its synthesizing enzyme; and both muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively). ACh modifies T and B cell function via both mAChR- and nAChR-mediated pathways. Stimulation of lymphocytes with the T cell activator phytohemagglutinin, protein kinase C activator phorbol ester, or cell surface molecules enhances the synthesis and release of ACh and up-regulates ChAT and/or M(5) mAChR gene expression. Furthermore, animal models of immune disorders exhibit abnormal lymphocytic cholinergic activity. The cholesterol-lowering drug simvastatin attenuates the lymphocytic cholinergic activity of T cells by inhibiting LFA-1 signaling in a manner independent of its cholesterol-lowering activity. This suggests that simvastatin exerts its immunosuppressive effects in part by modifying lymphocytic cholinergic activity. Nicotine, an active ingredient of tobacco, ameliorates ulcerative colitis but exacerbates Crohn's disease. Expression of mRNAs encoding the nAChR alpha7 and alpha5 subunits are significantly diminished in peripheral mononuclear leukocytes from smokers, as compared with those from nonsmokers. In addition, long-term exposure of lymphocytes to nicotine reduces intracellular Ca(2+) signaling via alpha7 nAChR-mediated pathways. In fact, studies of humoral antibody production in M(1)/M(5) mAChR-deficient and alpha7 nAChR-deficient animals revealed the role of lymphocytic cholinergic activity in the regulation of immune function. These results provide clues to understanding the mechanisms underlying immune system regulation and could serve as the basis for the development of new immunomodulatory drugs.
Topics: Acetylcholine; Animals; Antibodies, Monoclonal; Antigens, Surface; Humans; Immune System Diseases; Immunologic Factors; Immunotherapy; Lymphocytes; Neurons; Simvastatin
PubMed: 18285654
DOI: 10.1254/jphs.fm0070109 -
ELife Oct 2020Exercise has a wide range of systemic effects. In animal models, repeated exertion reduces malignant tumor progression, and clinically, exercise can improve outcome for...
Exercise has a wide range of systemic effects. In animal models, repeated exertion reduces malignant tumor progression, and clinically, exercise can improve outcome for cancer patients. The etiology of the effects of exercise on tumor progression are unclear, as are the cellular actors involved. We show here that in mice, exercise-induced reduction in tumor growth is dependent on CD8+ T cells, and that metabolites produced in skeletal muscle and excreted into plasma at high levels during exertion in both mice and humans enhance the effector profile of CD8+ T-cells. We found that activated murine CD8+ T cells alter their central carbon metabolism in response to exertion in vivo, and that immune cells from trained mice are more potent antitumor effector cells when transferred into tumor-bearing untrained animals. These data demonstrate that CD8+ T cells are metabolically altered by exercise in a manner that acts to improve their antitumoral efficacy.
Topics: Animals; Carcinogenesis; Cell Line, Tumor; Female; Mice; Physical Conditioning, Animal; T-Lymphocytes, Cytotoxic
PubMed: 33095157
DOI: 10.7554/eLife.59996 -
Frontiers in Immunology 2021Age-related changes of the immune system lead to an increased morbidity and mortality due to enhanced vulnerability to infectious diseases and malignancies. Recent...
Age-related changes of the immune system lead to an increased morbidity and mortality due to enhanced vulnerability to infectious diseases and malignancies. Recent studies revealed the important effects of physical activity on immune functions, which may largely depend on the type of exercise, its intensity and duration. However, limited information is available regarding the immunological effects of sport activities in older ages. The aim of our study was to examine the changes in a wide spectrum of lymphocyte subtypes after regular workout among healthy elderly individuals. We enrolled 29 elderly women with sedentary lifestyle (mean age: 67.03 ± 3.74 years) to take part in a 6-week long functional conditioning gymnastic exercise program. The percentages of peripheral natural killer (NK), NKT cells, T and B lymphocyte subtypes (early-/late-activated T, naïve and memory T, cytotoxic T (Tc), T-helper (Th)1, Th2, Th17, T regulatory type 1 (Tr1), CD4CD127CD25 Treg, as well as naïve and memory B cells) were determined by flow cytometry. Evaluation of the changes in functional capability of Treg cells was based on functional assays. At the end of exercise program, in parallel with improvements in body composition and physical performance, significant changes in naïve and memory lymphocyte ratios were observed. Importantly, levels of naïve Tc cells elevated, ratios of effector memory Tc cells decreased and distribution of memory B cells rearranged as well. Additionally, proportions of late-activated HLA-DR T cells increased, while percentages of anti-inflammatory interleukin (IL)-10 producing Tr1 cells, as well as immunosuppressive CD4CD127CD25 Treg cells decreased following the exercise workout. Changes observed after the regular exercise program indicate an improvement in the age-related redistribution of certain naïve and memory cell proportions and a retuned immune regulation in older ages.
Topics: Adaptive Immunity; Aged; Exercise; Female; Flow Cytometry; HLA-DR Antigens; Humans; Immunologic Memory; Lymphocyte Subsets; Male; Physical Conditioning, Human
PubMed: 33936054
DOI: 10.3389/fimmu.2021.639308 -
Pathogens and Disease Mar 2017Streptococcus pneumoniae (Spn) is a leading cause of community-acquired pneumonia, with infants and the elderly exhibiting significant susceptibility to the development...
Streptococcus pneumoniae (Spn) is a leading cause of community-acquired pneumonia, with infants and the elderly exhibiting significant susceptibility to the development of severe disease. A growing body of evidence supports the ability of Spn to negatively regulate the host response to infection, e.g. the capacity to induce death in numerous cell types. However, our understanding of the ability of Spn to directly impact lymphocytes remains limited. In this study, we tested the hypothesis that lymphocyte type and activation state influences the susceptibility to pneumococcus-mediated death. We show that in the resting state, CD4+ T cells exhibit a modestly increased susceptibility to Spn-induced death compared to CD8+ T cells or NK cells. In the presence of activating stimuli, the situation most reflective of what would occur in vivo during infection, all subsets demonstrated a significant increase in sensitivity to Spn-mediated death. Importantly, the activated subsets diverged dramatically in susceptibility with natural killer cells exhibiting an 8.6-fold greater sensitivity to pneumococcal components compared to the T-cell subsets. These results significantly expand our understanding of the capacity for pneumococcus to negatively regulate lymphocytes.
Topics: CD4-Positive T-Lymphocytes; Cell Death; Hemolysis; Humans; Killer Cells, Natural; Leukocytes, Mononuclear; Lymphocyte Activation; Lymphocytes; Streptococcus pneumoniae
PubMed: 28158464
DOI: 10.1093/femspd/ftx008 -
Journal of Virology Mar 1996The lytic cycle of Epstein-Barr virus (EBV) can be activated by transfection of the gene for ZEBRA, a viral basic-zipper (bZip) transcriptional activator. ZEBRA and... (Comparative Study)
Comparative Study
The lytic cycle of Epstein-Barr virus (EBV) can be activated by transfection of the gene for ZEBRA, a viral basic-zipper (bZip) transcriptional activator. ZEBRA and cellular AP-1 bZip activators, such as c-Fos, have homologous DNA-binding domains, and their DNA-binding specificities overlap. Moreover, EBV latency can also be disrupted by phorbol esters, which act, in part, through AP-1 activators. It is not known whether ZEBRA and AP-1 factors play equivalent roles in the initial stages of reactivation. Here the contribution of ZEBRA's basic DNA recognition domain to disruption of latency was analyzed by comparing ZEBRA with chimeric mutants in which the DNA recognition domain of ZEBRA was replaced with the analogous domain of c-Fos. Chimeric ZEBRA/c-Fos proteins overexpressed in Escherichia coli bound DNA with the specificity of c-Fos; they bound a heptamer AP-1 site and an octamer TPA response element (TRE). ZEBRA bound the AP-1 site and an array of ZEBRA response elements (ZREs). In assays with reporter genes, both ZEBRA and ZEBRA/c-Fos chimeric mutants activated transcription from Zp, a promoter of the ZEBRA gene (BZLF1) that contains the TRE and multiple ZREs. However, despite their capacity to activate reporters bearing Zp, neither ZEBRA nor the c-Fos chimeras activated transcription from Zp in the context of the intact latent viral genome. In contrast, ZEBRA but not ZEBRA/c-Fos chimeras activated Rp, a second viral promoter that controls ZEBRA expression. Hence, transcriptional autostimulation by transfected ZEBRA occurred preferentially at Rp. Both ZEBRA and the ZEBRA/c-Fos chimeras activated transcription from reporters with multimerized AP-1 sites. However, in the context of the virus, only ZEBRA activated the promoters of two early lytic cycle genes, BMRF1 and BMLF1, that contain an AP-1 site. Thus, overexpression of an activator that recognized AP-1 and TRE sites was not sufficient to activate EBV early lytic cycle genes.
Topics: B-Lymphocytes; Base Sequence; Cell Line; DNA; DNA-Binding Proteins; Escherichia coli; Gene Expression Regulation, Viral; Genes, Reporter; Herpesvirus 4, Human; Humans; Molecular Sequence Data; Protein Binding; Proto-Oncogene Proteins c-fos; Recombinant Fusion Proteins; Trans-Activators; Transcriptional Activation; Viral Proteins; Virus Latency
PubMed: 8627667
DOI: 10.1128/JVI.70.3.1493-1504.1996 -
Scandinavian Journal of Immunology Dec 2005The mitogen-activated protein kinase (MAPK) ERK5 plays an important role in mammary epithelial proliferation, endothelial cell survival and normal embryonic development....
The mitogen-activated protein kinase (MAPK) ERK5 plays an important role in mammary epithelial proliferation, endothelial cell survival and normal embryonic development. In nonhaematopoietic cells, mitogenic and stress signals activate the ERK5 cascade. Here, we investigated the role of the ERK5 pathway in T-cell activation and show that primary and leukaemic T cells express ERK5, whose activating phosphorylation is induced by antibodies against CD3 but not by phorbol myristate acetate treatment. ERK5 localized in the cytosol and nucleus in quiescent and activated T cells. In the latter, ERK5 phosphorylation was mainly observed in the nucleus. Selective activation of the ERK5 cascade by transfecting constitutively active MEK5 and wildtype ERK5 induced a reporter gene driven by the IL-2 promoter while barely affecting CD69 expression. These results suggest a new role for the ERK5 cascade in intracellular signalling in T cells.
Topics: Animals; Antibodies; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; CD3 Complex; Humans; Interleukin-2; Jurkat Cells; Lectins, C-Type; Lymphocyte Activation; Mice; Mitogen-Activated Protein Kinase 7; Phosphorylation; Promoter Regions, Genetic; Signal Transduction; T-Lymphocytes; Tetradecanoylphorbol Acetate
PubMed: 16316418
DOI: 10.1111/j.1365-3083.2005.01696.x