scholarly journals Vitamin D and the Immune System

2021 ◽  
Author(s):  
Vikram Singh Chauhan
Keyword(s):  
Vitamin D ◽  
Immune System ◽  
Immune Responses ◽  
Interleukin 1 ◽  
Cell Types ◽  
Surface Proteins ◽  
Target Cells ◽  
B Cell Differentiation ◽  
Regulatory T Lymphocytes ◽  
Factor Α

In the past few decades, various novel actions of vitamin D have been discovered. The mechanism of action of calcitriol or vitamin D is mediated by the Vitamin D receptor (VDR), a subfamily of nuclear receptors, which acts as a transcription factor in the target cells after formation of a heterodimer with the retinoid X receptor (RXR). As the VDR has been found in virtually all cell types, vitamin D exerts multiple actions on different tissues. Vitamin D has important immunomodulatory actions, which includes enhancement of the innate immune system and inhibition of the adaptative immune responses. These actions are associated with an increase in production of interleukin (IL)-4 by T helper (Th)-2 lymphocytes and the up-regulation of regulatory T lymphocytes. Vitamin D can regulate the immune responses in secondary lymphoid organs as well as in target organs through a number of mechanisms. Vitamin D inhibits the expression of APC cytokines, such as interleukin-1 (IL-1), IL-6, IL-12, and tissue necrosis factor- α (TNF-α) and decreases the expression of a set of major histocompatibility complex (MCH) class II cell surface proteins in macrophages. Vitamin D also inhibits B cell differentiation and antibody production. These actions reflect an important role of Vitamin D in balancing the immune system.

scholarly journals Low-Phosphate-Dependent Invasion Resembles a General Way for Neisseria gonorrhoeae To Enter Host Cells

2006 ◽  
Vol 74 (7) ◽  
pp. 4266-4273 ◽  
Author(s):  
Christiane Kühlewein ◽  
Cindy Rechner ◽  
Thomas F. Meyer ◽  
Thomas Rudel
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Rho Gtpases ◽  
Wide Spectrum ◽  
Cell Types ◽  
Surface Proteins ◽  
Host Cells ◽  
Animal Origin ◽  
Target Cells ◽  
Pit Formation ◽  
Serious Disease

ABSTRACT Obligate human-pathogenic Neisseria gonorrhoeae expresses numerous variant surface proteins mediating adherence to and invasion of target cells. The invariant major outer membrane porin PorB of serotype A (P.IA) gonococci triggers invasion into Chang cells only if the medium is devoid of phosphate. Since gonococci expressing PorBIA are frequently isolated from patients with severe disseminating infections, the interaction initiated by the porin may be of major relevance for the development of this serious disease. Here, we investigated the low-phosphate-dependent invasion and compared it to the well-known pathways of entry initiated by Opa proteins. P.IA-triggered invasion requires clathrin-coated pit formation and the action of actin and Rho GTPases. However, in contrast to Opa-initiated invasion via heparan sulfate proteoglycans, microtubules, acidic sphingomyelinase, phosphatidylinositol 3-kinase, and myosin light chain kinase are not involved in this entry pathway. Nor are Src kinases required, as they are in invasion, e.g., via the CEACAM3 receptor. Invasion by PorBIA occurs in a wide spectrum of cell types, such as primary human epithelial and endothelial cells and in cancer cells of human and animal origin. Low-phosphate-dependent invasion is thus a pathway of gonococcal entry distinct from Opa-mediated invasion.

scholarly journals Comprehensive multi-omics single-cell data integration reveals greater heterogeneity in the human immune system

2021 ◽  
Author(s):  
Congmin Xu ◽  
Junkai Yang ◽  
Astrid Kosters ◽  
Benjamin R Babcock ◽  
Peng Qiu ◽  
...  
Keyword(s):  
Immune System ◽  
Single Cell ◽  
Immune Cell ◽  
Cell Types ◽  
Cell Receptor ◽  
Surface Proteins ◽  
Cell Type ◽  
Human Immune System ◽  
Receptor Repertoire ◽  
Human Immune

Single-cell transcriptomics enables the definition of diverse human immune cell types across multiple tissue and disease contexts. Still, deeper biological understanding requires comprehensive integration of multiple single-cell omics (transcriptomic, proteomic, and cell receptor repertoire). To improve the identification of diverse cell types and the accuracy of cell-type classification in our multi-omics single-cell datasets, we developed SuPERR-seq, a novel analysis workflow to increase the resolution and accuracy of clustering and allow for the discovery and characterization of previously hidden cell subsets. We show that by incorporating information from cell-surface proteins and immunoglobulin transcript counts, we accurately remove cell doublets and prevent widespread cell-type misclassification. This approach uniquely improves the identification of heterogeneous cell types in the human immune system, including a novel subset of antibody-secreting cells in the bone marrow.

Pulmonary alveolar epithelial inducible NO synthase gene expression: regulation by inflammatory mediators

1995 ◽  
Vol 268 (3) ◽  
pp. L501-L508 ◽  
Author(s):  
H. H. Gutierrez ◽  
B. R. Pitt ◽  
M. Schwarz ◽  
S. C. Watkins ◽  
C. Lowenstein ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Gene Expression Regulation ◽  
Interleukin 1 ◽  
Alveolar Epithelium ◽  
Cell Types ◽  
Oxidation Products ◽  
No Oxidation ◽  
Target Cells ◽  
Cell Permeabilization ◽  
Necrosis Factor Alpha

Nitric oxide (.NO) is a short-lived mediator that can be induced by different cytokines and lipopolysaccharide (LPS) in a variety of cell types and produces many physiological and metabolic changes in target cells. In the current study, we show that a combination of cytokines, LPS, and zymosan-activated serum (ZAS; called for convenience cytomix Z) induces production of high concentrations of the NO oxidation products nitrite (NO2-) and nitrate (NO3-) by cultured rat fetal lung epithelial type II cells in a time-dependent fashion. Interferon-gamma and tumor necrosis factor-alpha alone did not significantly affect .NO synthesis, whereas ZAS, LPS, and interleukin-1 beta caused only a modest increase in formation of .NO oxidation products. Production of NO2- and NO3- was inhibited by NG-monomethyl-L-arginine and cyclohexmide. After exposure of these cells to a combination of the above cytokines, Escherichia coli LPS, and ZAS (cytomix Z), enhanced inducible nitric oxide synthase (iNOS) expression was indicated by an elevation in steady-state mRNA specific for iNOS (via Northern blot analysis) and increased immunofluorescence for iNOS after cell permeabilization, incubation with anti-iNOS antibody, and treatment with Cy3.18-conjugated rabbit-specific antibody. The extent of inflammatory mediator-induced.NO production by alveolar epithelium, which exceeds that of other lung cell types, reveals new insight into mechanisms of pulmonary host defense and pathways of free radical-mediated lung injury.

A circulating microvesicle-based biosignature for the detection of colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 373-373 ◽  
Author(s):  
D. Spetzler ◽  
T. Tinder ◽  
S. Kankipati ◽  
M. Maheshwari ◽  
C. D. Kuslich
Keyword(s):  
Colorectal Cancer ◽  
Surface Membrane ◽  
Stage Iv ◽  
Target Surface ◽  
Cell Types ◽  
Surface Proteins ◽  
Target Cells ◽  
Cell Of Origin ◽  
Protein Biomarkers ◽  
Multiplexed Immunoassay

373 Background: Microvesicles are principally derived either from the endosomal pathway (as exosomes) or shed directly from the plasma membrane. They are between 40-500 nm in diameter and are secreted by most cell types, including tumor cells. In circulation, microvesicles appear to participate in cellular communication by transporting mRNAs, miRs and proteins from their cell of origin to target cells where they can elicit biological responses. The quantity and protein topography of microvesicles shed from cancer cells varies considerably compared to those shed from normal cells. Thus, the concentration of circulating plasma microvesicles with molecular markers indicative of the disease state can be used as a robust and informative blood-based biosignature. In this study we report the results of the application of a novel multiplexed method for quantifying and profiling microvesicles in plasma for the detection of colorectal cancer. Methods: We have developed a versatile mulitplexed microvesicle-based discovery panel with 73 different antibodies that target surface proteins of various microvesicle subpopulations. This system was used to develop a microvesicle-derived biosignature composed of 2 different surface membrane protein biomarkers. Results: In this study, we demonstrate that a combination of TMEM211 and CD24 provide a robust signature for the detection of colorectal cancer (CRC). We isolated microvesicles from plasma of 257 patients with CRC, 57 stage I, 104 stage II, 80 stage 3, 6 stage IV, and 11 of unknown stage; 327 self-described, age-range matched normal plasma specimens were used for the control population. The level of TMEM211 and CD24 containing microvesicles for these samples was determined using a multiplexed immunoassay. Thresholds were empirically determined to maximize the sensitivity and specificity of CRC detection, resulting in a sensitivity of 90% with a specificity of 85% with an AUC of .91. Conclusions: This study demonstrates that it is possible to use circulating microvesicles for the development of a highly sensitive and specific blood-based assay to detect CRC. [Table: see text]

The innate immune system

2020 ◽  
pp. 307-314
Author(s):  
Paul Bowness
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Innate Immune System ◽  
Cell Types ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Innate Immune Responses ◽  
Adaptive Immune ◽  
System P ◽  
Different Cell Types

The innate immune system comprises evolutionarily ancient mechanisms that mediate first-line responses against microbial pathogens, and are also important in priming and execution of adaptive immune responses, and in defence against tumours. These responses, which recognize microbial non-self, damaged self, and absent self, are characterized by rapidity of action and they involve various different cell types, cell-associated receptors, and soluble factors. Previously thought to lack plasticity or memory, certain innate immune responses have recently been shown to be capable of ‘learning’ or ‘training’. Most cells of the innate immune system are derived from the myeloid precursors in the bone marrow. These include monocytes and their derivatives—macrophages and dendritic cells, blood granulocytes (neutrophils, basophils, and eosinophils), and tissue mast cells.

scholarly journals Vitamin D3and the immune system: maintaining the balance in health and disease

2007 ◽  
Vol 20 (1) ◽  
pp. 106-118 ◽  
Author(s):  
Femke Baeke ◽  
Evelyne Van Etten ◽  
Lut Overbergh ◽  
Chantal Mathieu
Keyword(s):  
Vitamin D ◽  
T Cells ◽  
Immune System ◽  
Animal Models ◽  
Autoimmune Diseases ◽  
Active Form ◽  
Epidemiological Data ◽  
Cell Types ◽  
Dihydroxyvitamin D

1,25-Dihydroxyvitamin D3(1,25(OH)2D3), the active form of vitamin D3, is a central player in Ca and bone metabolism. More recently, important immunomodulatory effects have been attributed to this hormone. By binding to its receptor, the vitamin D receptor, 1,25(OH)2D3regulates the expression of various genes and consequently affects the behaviour of different cell types within the immune system. 1,25(OH)2D3can potently inhibit pathogenic T cells and gives rise to elevated numbers of regulatory T cells via the induction of tolerogenic dendritic cells. These immunomodulatory activities of 1,25(OH)2D3have also been proven usefulin vivo: administration of 1,25(OH)2D3in several animal models can prevent or cure different autoimmune diseases and graft rejection. To overcome the dose-limiting side effects of 1,25(OH)2D3on Ca and bone, less calcaemic structural analogues (alone or in combination with synergistically acting drugs or bone-resorption inhibitors) have been successfully used in animal models. Furthermore, as 1,25(OH)2D3also contributes to host defence against infectious agents by the induction of antimicrobial responses, this molecule might provide a new strategy to deal with drug-resistant infections. According to the pleiotropic effects of 1,25(OH)2D3in the immune system, increasing epidemiological data underline the importance of adequate vitamin D intakes in reducing the risk of several autoimmune diseases and infections such as tuberculosis.

scholarly journals Aging-Related Cellular, Structural and Functional Changes in the Lymph Nodes: A Significant Component of Immunosenescence? An Overview

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3148
Author(s):  
Marta Cakala-Jakimowicz ◽  
Paulina Kolodziej-Wojnar ◽  
Monika Puzianowska-Kuznicka
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Lymph Nodes ◽  
Immune Cell ◽  
Humoral Response ◽  
The Elderly ◽  
Cell Types ◽  
Functional Changes ◽  
B Cell Homeostasis

Aging affects all tissues and organs. Aging of the immune system results in the severe disruption of its functions, leading to an increased susceptibility to infections, an increase in autoimmune disorders and cancer incidence, and a decreased response to vaccines. Lymph nodes are precisely organized structures of the peripheral lymphoid organs and are the key sites coordinating innate and long-term adaptive immune responses to external antigens and vaccines. They are also involved in immune tolerance. The aging of lymph nodes results in decreased cell transport to and within the nodes, a disturbance in the structure and organization of nodal zones, incorrect location of individual immune cell types and impaired intercellular interactions, as well as changes in the production of adequate amounts of chemokines and cytokines necessary for immune cell proliferation, survival and function, impaired naïve T- and B-cell homeostasis, and a diminished long-term humoral response. Understanding the causes of these stromal and lymphoid microenvironment changes in the lymph nodes that cause the aging-related dysfunction of the immune system can help to improve long-term immune responses and the effectiveness of vaccines in the elderly.

149 PRODUCTION OF KNOCK-DOWN MICE WITH shRNA CYTOCHROME P-450 4F16 GENE AND REDUCTION OF THE IMMUNE SYSTEM

2012 ◽  
Vol 24 (1) ◽  
pp. 187
Author(s):  
B. C. Yang ◽  
K. C. Hwang ◽  
K. W. Kim ◽  
H. C. Lee ◽  
H. J. Chung ◽  
...  
Keyword(s):  
Immune System ◽  
Interleukin 1 ◽  
Interleukin 10 ◽  
Wild Type ◽  
Knock Down ◽  
Tnf Α ◽  
C57bl Mice ◽  
Mrna And Protein Expression ◽  
Factor Α ◽  
Cytochrome P 450

The putative mouse homologue of cytochrome P-450 4F16 (Cyp4f16) is induced by interleukin-1 (Il-1), interleukin-6 (Il-6) and tumour necrosis factor-α (Tnf-α) and repressed by interleukin-10 (Il-10) and lipopolysaccharide (LPS). The Cyp4F16 is a subfamily of Cyp4F and it is also related to eicosanoids that are important mediators in the inflammatory cascade (Cui et al. 2001). To investigate the role of Cyp4F16, in the present study, we report the production of Cyp4f16 gene knock-down mice in 2 strains of mice, namely A/J and C57BL/6. The A/J is susceptible to infection and it is associated with Cyp4F16, whereas C57BL/6 is relatively resistant to infection. An shRNA-Cyp4F16 expression vector was microinjected into pronuclei of fertilized mouse oocytes and the embryos were transferred into pseudopregnant recipients. As a result, 25 and 50 mice were produced in the A/J and C57BL, respectively. Two mice in the A/J strain and 6 in the C57BL strain were confirmed by PCR as transgenic. Organs were collected in each of the lines produced by inbreeding and screened with real-time PCR for Cyp4f16 transcripts. The Cyp4f16 gene was expressed in a tissue-specific manner with high expression in the pancreas, spleen and lung and a lower level of transcription in the heart, muscle, thymus, kidney, testis and liver. In the spleen of transgenic Cyp4f16 knock-down mice, Cyp4f16 mRNA and protein expression levels were significantly lower than those of wild-type mice. The A/J Cyp4f16 knock-down mice suffered an inflammatory skin disease and tumours, but wild-type A/J mice and knock-down C57BL mice did not. Taken together, these results suggest that Cyp4f16 may play a regulatory role in the immune system and point to the use of the Cyp4f16 knock-down mouse as an experimental animal model for the study of the inflammatory process. This work was supported by a grant PJ0070762010 from BioGreen 21 Program, Rural Development Administration, Republic of Korea.

scholarly journals Differences of plasma IL-1 and TNF-α in healthy Chinese Population

Open Medicine ◽  
2015 ◽  
Vol 10 (1) ◽  
Author(s):  
Jintao Yuan ◽  
Lan Wang ◽  
Yijin Lin ◽  
Jianhong Chen ◽  
Jianghong Hu
Keyword(s):  
Immune Responses ◽  
Opportunistic Infections ◽  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Predictive Biomarkers ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α ◽  
Inflammatory Processes ◽  
Factor Α ◽  
Necrosis Factor

AbstractPle iotropic proinflammatory cytokines, interleukin- 1 (IL-1) and tumor necrosis factor-α (TNF-α), involved in the regulations of various immune responses, inflammatory processes and hematopoiesis. In the present study, the expression levels of IL-1 and TNF-α were detected by enzyme-linked immunosorbent assay (ELISA). Following the cytokine blockade as a successful clinical therapy for autoimm une diseases such as rheumatoid arthritis, the patients are more susceptible to a variety of opportunistic infections. IL-1 and TNF-α may be useful predictive biomarkers of diseases and offer potential targets for therapeutic intervention of inflammatory diseases. However, our results showed that the plasma IL-1 level was significantly higher in women compared to men (69.5 ± 19.8 pg/ ml in men and 80.1 ± 19.5 pg/ml in women, respectively); the plasma levels of TNF-α were higher in men than women (20.8 ± 4.9 pg/ml and 18.7 ± 7.1 pg/ml, respectively). The significant gender difference of plasma interleukin-1 (IL-1) and TNF-α levels present in healthy adults in Jiangsu Province, China (P=0.002 and P=0.015, respectively), and may be as a hint for sex differences of susceptibility to many diseases and elementary immune response.

scholarly journals SLAM Family Receptor Signaling in Viral Infections: HIV and Beyond

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 184
Author(s):  
O’Connell ◽  
Amalfitano ◽  
Aldhamen
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Viral Infections ◽  
Immune Cell ◽  
Adaptor Protein ◽  
Adaptor Proteins ◽  
Cell Types ◽  
Receptor Signaling ◽  
Slam Family ◽  
Signaling Lymphocytic Activation Molecule

The signaling lymphocytic activation molecule (SLAM) family of receptors are expressed on the majority of immune cells. These receptors often serve as self-ligands, and play important roles in cellular communication and adhesion, thus modulating immune responses. SLAM family receptor signaling is differentially regulated in various immune cell types, with responses generally being determined by the presence or absence of two SLAM family adaptor proteins—Ewing’s sarcoma-associated transcript 2 (EAT-2) and SLAM-associated adaptor protein (SAP). In addition to serving as direct regulators of the immune system, certain SLAM family members have also been identified as direct targets for specific microbes and viruses. Here, we will discuss the known roles for these receptors in the setting of viral infection, with special emphasis placed on HIV infection. Because HIV causes such complex dysregulation of the immune system, studies of the roles for SLAM family receptors in this context are particularly exciting.

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