scholarly journals The Good, the Bad, and the Ugly of Dendritic Cells during Prion Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Neil Andrew Mabbott ◽  
Barry Matthew Bradford
Keyword(s):  
Dendritic Cells ◽  
Prion Diseases ◽  
The Body ◽  
Mononuclear Phagocytes ◽  
Diverse Range ◽  
Exposure Routes ◽  
Antigen Presenting ◽  
Secondary Lymphoid Organs ◽  
The Brain

Prions are a unique group of proteinaceous pathogens which cause neurodegenerative disease and can be transmitted by a variety of exposure routes. After peripheral exposure, the accumulation and replication of prions within secondary lymphoid organs are obligatory for their efficient spread from the periphery to the brain where they ultimately cause neurodegeneration and death. Mononuclear phagocytes (MNP) are a heterogeneous population of dendritic cells (DC) and macrophages. These cells are abundant throughout the body and display a diverse range of roles based on their anatomical locations. For example, some MNP are strategically situated to provide a first line of defence against pathogens by phagocytosing and destroying them. Conventional DC are potent antigen presenting cells and migrate via the lymphatics to the draining lymphoid tissue where they present the antigens to lymphocytes. The diverse roles of MNP are also reflected in various ways in which they interact with prions and in doing so impact on disease pathogenesis. Indeed, some studies suggest that prions exploit conventional DC to infect the host. Here we review our current understanding of the influence of MNP in the pathogenesis of the acquired prion diseases with particular emphasis on the role of conventional DC.

scholarly journals Fascinating Dendritic Cells—Sentinel Cells of the Immune System a Review

2021 ◽  
Vol 65 (4) ◽  
pp. 12-19
Author(s):  
Z. Kiššová ◽  
Ľ. Tkáčiková
Keyword(s):  
Dendritic Cells ◽  
Immune System ◽  
Experimental Models ◽  
The Body ◽  
Main Role ◽  
Tumour Immunity ◽  
System A ◽  
Antigen Presenting

Abstract Dendritic cells (DC) are specialized antigen presenting cells which have the unique ability to activate naive T-lymphocytes. Their role in the immune system is much more sophisticated than it seems, as they do not kill the pathogens directly, but provide a long-lasting antigen specific immune response thanks to that sufficiently bridging the innate and the adaptive immunity. In recent years, there has been a growing interest in studies of their role in immune regulation, autoimmune reactions, as well as in immune responses against pathogens and tumours. Processing and presentation capabilities of a highly specific and unique tumour antigen makes them an interesting tool for stimulating effective anti-tumour immunity. In vitro generations of DC represent a preferred model for more detailed studies of DC biology in other fields. The aim of this review was to discuss the main role of dendritic cells in the body as well as their current use as experimental models for further scientific studies.

scholarly journals Overview of Bovine Dendritic Cells

2018 ◽  
Vol 66 (3) ◽  
pp. 815-821 ◽  
Author(s):  
Lucie Kratochvílová ◽  
Petr Sláma
Keyword(s):  
Dendritic Cells ◽  
Immune System ◽  
Volume Ratio ◽  
The Body ◽  
Adaptive Immune ◽  
Prevention And Treatment ◽  
Bone Marrow Derived Cells ◽  
Antigen Presenting ◽  
Adaptive Immune Systems

This article is an overview of dendritic cells (DCs) in cattle. The understanding of the immune system and the role of DCs in many ways can contribute to their use in the prevention and treatment of many infectious and autoimmune diseases. DCs are bone marrow-derived cells that function as professional antigen presenting cells. They act as messengers between the innate and the adaptive immune systems. The morphology of DCs results in a very large surface to volume ratio. That is, the DCs have a very large surface area compared to the overall cell volume. Currently, most dendritic cells research occurs in the human and mice. There is a lack of studies in cattle describing DCs. DCs survey the body and collect information relevant to the immune system. They are then able to instruct and direct the adaptive arms to respond to challenges.

scholarly journals Millimeter (MM) wave and microwave frequency radiation produce deeply penetrating effects: the biology and the physics

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Martin L. Pall
Keyword(s):  
Magnetic Fields ◽  
Electric Fields ◽  
Cardiac Activity ◽  
Maximum Level ◽  
Voltage Sensor ◽  
The Body ◽  
Time Varying ◽  
The Brain ◽  
Mm Waves

Abstract Millimeter wave (MM-wave) electromagnetic fields (EMFs) are predicted to not produce penetrating effects in the body. The electric but not magnetic part of MM-EMFs are almost completely absorbed within the outer 1 mm of the body. Rodents are reported to have penetrating MM-wave impacts on the brain, the myocardium, liver, kidney and bone marrow. MM-waves produce electromagnetic sensitivity-like changes in rodent, frog and skate tissues. In humans, MM-waves have penetrating effects including impacts on the brain, producing EEG changes and other neurological/neuropsychiatric changes, increases in apparent electromagnetic hypersensitivity and produce changes on ulcers and cardiac activity. This review focuses on several issues required to understand penetrating effects of MM-waves and microwaves: 1. Electronically generated EMFs are coherent, producing much higher electrical and magnetic forces then do natural incoherent EMFs. 2. The fixed relationship between electrical and magnetic fields found in EMFs in a vacuum or highly permeable medium such as air, predicted by Maxwell’s equations, breaks down in other materials. Specifically, MM-wave electrical fields are almost completely absorbed in the outer 1 mm of the body due to the high dielectric constant of biological aqueous phases. However, the magnetic fields are very highly penetrating. 3. Time-varying magnetic fields have central roles in producing highly penetrating effects. The primary mechanism of EMF action is voltage-gated calcium channel (VGCC) activation with the EMFs acting via their forces on the voltage sensor, rather than by depolarization of the plasma membrane. Two distinct mechanisms, an indirect and a direct mechanism, are consistent with and predicted by the physics, to explain penetrating MM-wave VGCC activation via the voltage sensor. Time-varying coherent magnetic fields, as predicted by the Maxwell–Faraday version of Faraday’s law of induction, can put forces on ions dissolved in aqueous phases deep within the body, regenerating coherent electric fields which activate the VGCC voltage sensor. In addition, time-varying magnetic fields can directly put forces on the 20 charges in the VGCC voltage sensor. There are three very important findings here which are rarely recognized in the EMF scientific literature: coherence of electronically generated EMFs; the key role of time-varying magnetic fields in generating highly penetrating effects; the key role of both modulating and pure EMF pulses in greatly increasing very short term high level time-variation of magnetic and electric fields. It is probable that genuine safety guidelines must keep nanosecond timescale-variation of coherent electric and magnetic fields below some maximum level in order to produce genuine safety. These findings have important implications with regard to 5G radiation.

scholarly journals Role of ChemR23 in directing the migration of myeloid and plasmacytoid dendritic cells to lymphoid organs and inflamed skin

2005 ◽  
Vol 201 (4) ◽  
pp. 509-515 ◽  
Author(s):  
William Vermi ◽  
Elena Riboldi ◽  
Valerie Wittamer ◽  
Francesca Gentili ◽  
Walter Luini ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lupus Erythematosus ◽  
Normal Skin ◽  
Cell Monolayer ◽  
Lymphoid Organs ◽  
High Endothelial Venules ◽  
Luminal Side ◽  
Plasmacytoid Dcs ◽  
Secondary Lymphoid Organs

Chemerin is a chemotactic agent that was recently identified as the ligand of ChemR23, a serpentine receptor expressed by activated macrophages and monocyte-derived dendritic cells (DCs). This paper shows that blood plasmacytoid and myeloid DCs express functional ChemR23. Recombinant chemerin induced the transmigration of plasmacytoid and myeloid DCs across an endothelial cell monolayer. In secondary lymphoid organs (lymph nodes and tonsils), ChemR23 is expressed by CD123+ plasmacytoid DCs and by CD1a+ DC-SIGN+ DCs in the interfollicular T cell area. ChemR23+ DCs were also observed in dermis from normal skin, whereas Langerhans cells were negative. Chemerin expression was selectively detected on the luminal side of high endothelial venules in secondary lymphoid organs and in dermal endothelial vessels of lupus erythematosus skin lesions. Chemerin+ endothelial cells were surrounded by ChemR23+ plasmacytoid DCs. Thus, ChemR23 is expressed and functional in plasmacytoid DCs, a property shared only by CXCR4 among chemotactic receptors. This finding, together with the selective expression of the cognate ligand on the luminal side of high endothelial venules and inflamed endothelium, suggests a key role of the ChemR23/chemerin axis in directing plasmacytoid DC trafficking.

Expression of Tyk2 in dendritic cells is required for IL-12, IL-23, and IFN-γ production and the induction of Th1 cell differentiation

Blood ◽  
2007 ◽  
Vol 110 (2) ◽  
pp. 553-560 ◽  
Author(s):  
Naoki Tokumasa ◽  
Akira Suto ◽  
Shin-ichiro Kagami ◽  
Shunsuke Furuta ◽  
Koichi Hirose ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cell Differentiation ◽  
Cpg Odn ◽  
T Helper ◽  
Dc Functions ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Ifn Γ ◽  
Antigen Presenting

Abstract It is well documented that dendritic cells (DCs), representative antigen-presenting cells, are important sources of Th1-promoting cytokines and are actively involved in the regulation of T-helper–cell differentiation. However, the intracellular event that regulates this process is still largely unknown. In this study, we examined the role of Tyk2, a JAK kinase that is involved in the signaling pathway under IL-12 and IL-23, in DC functions. While the differentiation and maturation of DCs was normal in Tyk2-deficient (Tyk2−/−) mice, IL-12–induced Stat4 phosphorylation was diminished in Tyk2−/− DCs. IL-12–induced IFN-γ production was also significantly diminished in Tyk2−/− DCs to levels similar to those in Stat4−/− DCs. Interestingly, Tyk2−/− DCs were defective in IL-12 and IL-23 production upon stimulation with CpG ODN. Furthermore, Tyk2−/− DCs were impaired in their ability to induce Th1-cell differentiation but not Th2-cell differentiation. Taken together, these results indicate that the expression of Tyk2 in DCs is crucial for the production of Th1-promoting cytokines such as IL-12 and IFN-γ from DCs and thereby for the induction of antigen-specific Th1-cell differentiation.

CCM3 Loss-Induced Lymphatic Defect Is Mediated by the Augmented VEGFR3-ERK1/2 Signaling

2021 ◽  
Author(s):  
Lingfeng Qin ◽  
Haifeng Zhang ◽  
Busu Li ◽  
Quan Jiang ◽  
Francesc Lopez ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Fluorescein Isothiocyanate ◽  
The Body ◽  
Blue Dye ◽  
Transcriptional Level ◽  
Dependent Manner ◽  
Cavernous Malformations ◽  
Morphological Alterations ◽  
The Brain

Objective: Cerebral cavernous malformations (CCMs) can happen anywhere in the body, although they most commonly produce symptoms in the brain. The role of CCM genes in other vascular beds outside the brain and retina is not well-examined, although the 3 CCM-associated genes ( CCM1 , CCM2 , and CCM3 ) are ubiquitously expressed in all tissues. We aimed to determine the role of CCM gene in lymphatics. Approach and Results: Mice with an inducible pan–endothelial cell (EC) or lymphatic EC deletion of Ccm3 ( Pdcd10 ECKO or Pdcd10 LECKO ) exhibit dilated lymphatic capillaries and collecting vessels with abnormal valve structure. Morphological alterations were correlated with lymphatic dysfunction in Pdcd10 LECKO mice as determined by Evans blue dye and fluorescein isothiocyanate(FITC)-dextran transport assays. Pdcd10 LECKO lymphatics had increased VEGFR3 (vascular endothelial growth factor receptor-3)-ERK1/2 signaling with lymphatic hyperplasia. Mechanistic studies suggested that VEGFR3 is primarily regulated at a transcriptional level in Ccm3-deficient lymphatic ECs, in an NF-κB (nuclear factor κB)–dependent manner. CCM3 binds to importin alpha 2/KPNA2 (karyopherin subunit alpha 2), and a CCM3 deletion releases KPNA2 to activate NF-κB P65 by facilitating its nuclear translocation and P65-dependent VEGFR3 transcription. Moreover, increased VEGFR3 in lymphatic EC preferentially activates ERK1/2 signaling, which is critical for lymphatic EC proliferation. Importantly, inhibition of VEGFR3 or ERK1/2 rescued the lymphatic defects in structure and function. Conclusions: Our data demonstrate that CCM3 deletion augments the VEGFR3-ERK1/2 signaling in lymphatic EC that drives lymphatic hyperplasia and malformation and warrant further investigation on the potential clinical relevance of lymphatic dysfunction in patients with CCM.

scholarly journals Regulation of the Migration of Distinct Dendritic Cell Subsets

2021 ◽  
Vol 9 ◽  
Author(s):  
Meng Feng ◽  
Shuping Zhou ◽  
Yong Yu ◽  
Qinghong Su ◽  
Xiaofan Li ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Immune Responses ◽  
The Body ◽  
Inflammatory Factors ◽  
Pathogenic Microorganisms ◽  
Migration Patterns ◽  
Dendritic Cell Subsets ◽  
And Migration ◽  
Antigen Presenting

Dendritic cells (DCs), a class of antigen-presenting cells, are widely present in tissues and apparatuses of the body, and their ability to migrate is key for the initiation of immune activation and tolerogenic immune responses. The importance of DCs migration for their differentiation, phenotypic states, and immunologic functions has attracted widespread attention. In this review, we discussed and compared the chemokines, membrane molecules, and migration patterns of conventional DCs, plasmocytoid DCs, and recently proposed DC subgroups. We also review the promoters and inhibitors that affect DCs migration, including the hypoxia microenvironment, tumor microenvironment, inflammatory factors, and pathogenic microorganisms. Further understanding of the migration mechanisms and regulatory factors of DC subgroups provides new insights for the treatment of diseases, such as infection, tumors, and vaccine preparation.

scholarly journals Dendritic cells mediate the induction of polyfunctional human IL17-producing cells (Th17-1 cells) enriched in the bone marrow of patients with myeloma

Blood ◽  
2008 ◽  
Vol 112 (7) ◽  
pp. 2878-2885 ◽  
Author(s):  
Kavita M. Dhodapkar ◽  
Scott Barbuto ◽  
Phillip Matthews ◽  
Anjli Kukreja ◽  
Amitabha Mazumder ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Th17 Cells ◽  
T Helper ◽  
Tumor Bed ◽  
Distinct Lineage ◽  
Human Dendritic Cells ◽  
Antigen Presenting ◽  
Dc Maturation

Abstract IL17-producing (Th17) cells are a distinct lineage of T helper cells that regulate immunity and inflammation. The role of antigen-presenting cells in the induction of Th17 cells in humans remains to be fully defined. Here, we show that human dendritic cells (DCs) are efficient inducers of Th17 cells in culture, including antigen-specific Th17 cells. Although most freshly isolated circulating human Th17 cells secrete IL17 alone or with IL2, those induced by DCs are polyfunctional and coexpress IL17 and IFNγ (Th17-1 cells). The capacity of DCs to expand Th17-1 cells is enhanced upon DC maturation, and mature DCs are superior to monocytes for the expansion of autologous Th17 cells. In myeloma, where tumors are infiltrated by DCs, Th17 cells are enriched in the bone marrow relative to circulation. Bone marrow from patients with myeloma contains a higher proportion of Th17-1 cells compared with the marrow in preneoplastic gammopathy (monoclonal gammopathy of undetermined significance [MGUS]). Uptake of apoptotic but not necrotic myeloma tumor cells by DCs leads to enhanced induction of Th17-1 cells. These data demonstrate the capacity of DCs to induce expansion of polyfunctional IL17-producing T cells in humans, and suggest a role for DCs in the enrichment of Th17-1 cells in the tumor bed.

ATP-binding cassette transporters and neurodegenerative diseases

2021 ◽  
Author(s):  
Jared S. Katzeff ◽  
Woojin Scott Kim
Keyword(s):  
Neurodegenerative Diseases ◽  
Abc Transporters ◽  
Brain Diseases ◽  
Atp Binding ◽  
Future Directions ◽  
Diverse Range ◽  
The Brain ◽  
Lateral Sclerosis ◽  
Atp Binding Cassette

Abstract ATP-binding cassette (ABC) transporters are one of the largest groups of transporter families in humans. ABC transporters mediate the translocation of a diverse range of substrates across cellular membranes, including amino acids, nucleosides, lipids, sugars and xenobiotics. Neurodegenerative diseases are a group of brain diseases that detrimentally affect neurons and other brain cells and are usually associated with deposits of pathogenic proteins in the brain. Major neurodegenerative diseases include Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. ABC transporters are highly expressed in the brain and have been implicated in a number of pathological processes underlying neurodegenerative diseases. This review outlines the current understanding of the role of ABC transporters in neurodegenerative diseases, focusing on some of the most important pathways, and also suggests future directions for research in this field.

Infection and immunity

2021 ◽  
pp. 853-920
Keyword(s):  
Major Histocompatibility Complex ◽  
Immune System ◽  
Cell Types ◽  
The Body ◽  
Acquired Immunity ◽  
Histocompatibility Complex ◽  
Repair Mechanisms ◽  
Antigen Presenting ◽  
Different Cell Types

‘Infection and immunity’ considers the response of the body to pathogens, such as bacteria, viruses, prions, fungi, and parasites, which are discussed in terms of their nature, life cycle, and modes of infection. The role of the immune system in defence against infection is discussed, including innate and adaptive (acquired) immunity, antigens, the major histocompatibility complex, and the different cell types involved (antigen-presenting cells, T-cells, and B-cells). The mechanisms and cellular basis of inflammation are considered, as are post-infection repair mechanisms, and pathologies of the immune system such as hypersensitivity, autoimmunity and transplantations, and immunodeficiency (both primary and secondary to other diseases).

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