The Dialect of Immune System in the CNS: The Nervous Tissue as an Immune Compartment for T Cells and Dendritic Cells

2008 ◽  
pp. 197-221
Author(s):  
Z. Fabry ◽  
E. Reinke ◽  
A. Zozulya ◽  
M. Sandor ◽  
I. Bechmann
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune System ◽  
Nervous Tissue

scholarly journals Common variable immunodeficiency – case report

2013 ◽  
Vol 3 (2) ◽  
pp. 170-172
Author(s):  
Emina Vukas ◽  
Aida Dizdarević ◽  
Senka Mesihović - Dinarević ◽  
Adisa Čengić
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Case Report ◽  
Immune System ◽  
Primary Immunodeficiency ◽  
Common Variable Immunodeficiency ◽  
Clinical Picture ◽  
Clinical Signs ◽  
Common Variable

Common variable immunodeficiency (CVID) or acquired hypogammaglobulinemia is the type of primary immunodeficiency. Deregulation of the immune system, leading to hypogammaglobulinemia, defective activation and proliferation of T cells and dendritic cells, and malfunction of the cytokines are observed in CVID. The clinical picture of CVID varies, any organ or system can be affected, therefore the diagnosis is often difficult and delayed and sometimes is not always possible. This article describes a twelve years old boy with all the clinical signs of immunodeficiency, as confi rmed by laboratory. The main treatment consists of life-long immunoglobulin substitution in intravenous or subcutaneous form.

scholarly journals Environmental signals rather than layered ontogeny imprint the function of type 2 conventional dendritic cells in young and adult mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nikos E. Papaioannou ◽  
Natallia Salei ◽  
Stephan Rambichler ◽  
Kaushikk Ravi ◽  
Jelena Popovic ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune System ◽  
Early Life ◽  
Adult Life ◽  
Lymphoid Cells ◽  
Environmental Signals ◽  
Cell Responses ◽  
Adult Mice

AbstractConventional dendritic cells (cDC) are key activators of naive T cells, and can be targeted in adults to induce adaptive immunity, but in early life are considered under-developed or functionally immature. Here we show that, in early life, when the immune system develops, cDC2 exhibit a dual hematopoietic origin and, like other myeloid and lymphoid cells, develop in waves. Developmentally distinct cDC2 in early life, despite being distinguishable by fate mapping, are transcriptionally and functionally similar. cDC2 in early and adult life, however, are exposed to distinct cytokine environments that shape their transcriptional profile and alter their ability to sense pathogens, secrete cytokines and polarize T cells. We further show that cDC2 in early life, despite being distinct from cDC2 in adult life, are functionally competent and can induce T cell responses. Our results thus highlight the potential of harnessing cDC2 for boosting immunity in early life.

β2-Microglobulin as a negative regulator of the immune system: high concentrations of the protein inhibit in vitro generation of functional dendritic cells

Blood ◽  
2003 ◽  
Vol 101 (10) ◽  
pp. 4005-4012 ◽  
Author(s):  
Jin Xie ◽  
Ying Wang ◽  
Muta E. Freeman ◽  
Bart Barlogie ◽  
Qing Yi
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune System ◽  
Map Kinases ◽  
Negative Impact ◽  
Elevated Serum ◽  
T Cell Response ◽  
Negative Regulator ◽  
Β2 Microglobulin ◽  
High Concentrations

Abstract Two common features in human immunodeficiency virus infection and acquired immunodeficiency syndrome, rheumatoid arthritis, and hematologic malignancies including multiple myeloma are elevated serum levels of β2-microglobulin (β2M) and activation or inhibition of the immune system. We hypothesized that β2M at high concentrations may have a negative impact on the immune system. In this study, we examined the effects of β2M on monocyte-derived dendritic cells (MoDCs). The addition of β2M (more than 10 μg/mL) to the cultures reduced cell yield, inhibited the up-regulation of surface expression of human histocompatibility leukocyte antigen (HLA)–ABC, CD1a, and CD80, diminished their ability to activate T cells, and compromised generation of the type-1 T-cell response induced in allogeneic mixed-lymphocyte reaction. Compared with control MoDCs, β2M-treated cells produced more interleukin-6 (IL-6), IL-8, and IL-10. β2M-treated cells expressed significantly fewer surface CD83, HLA-ABC, costimulatory molecules, and adhesion molecules and were less potent at stimulating allospecific T cells after an additional 48-hour culture in the presence of tumor necrosis factor-α and IL-1β. During cell culture, β2M down-regulated the expression of phosphorylated mitogen-activated protein (MAP) kinases, extracellular signal-related kinase (ERK), and mitogen-induced extracellular kinase (MEK), inhibited nuclear factor-κB (NF-κB), and activated signal transducer and activator of transcription-3 (STAT3) in treated cells, all of which are involved in cell differentiation and proliferation. Thus, our study demonstrates that β2M at high concentrations retards the generation of MoDCs, which may involve down-regulation of major histocompatibility complex class I molecules, inactivation of Raf/MEK/ERK cascade and NF-κB, and activation of STAT3, and it merits further study to elucidate the underlying mechanisms.

scholarly journals The Role of Forkhead Box 1 (FOXO1) in the Immune System: Dendritic Cells, T Cells, B Cells, and Hematopoietic Stem Cells

2017 ◽  
Vol 37 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Adriana Alicia Cabrera-Ortega ◽  
Daniel Feinberg ◽  
Youde Liang ◽  
Carlos Rossa ◽  
Dana T. Graves
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Dendritic Cells ◽  
Immune System ◽  
B Cells ◽  
Hematopoietic Stem Cells ◽  
Hematopoietic Stem ◽  
Forkhead Box

The role of dendritic cells in shaping the immune response

2004 ◽  
Vol 5 (2) ◽  
pp. 191-195 ◽  
Author(s):  
C. J. Howard ◽  
B. Charleston ◽  
S. A. Stephens ◽  
P. Sopp ◽  
J. C. Hope
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune System ◽  
Innate Immune System ◽  
Adaptive Response ◽  
Ex Vivo ◽  
T Cell Response ◽  
Innate Immune ◽  
Myeloid Dendritic Cells

AbstractDendritic cells are central to the initiation of primary immune responses. They are the only antigen-presenting cell capable of stimulating naive T cells, and hence they are pivotal in the generation of adaptive immunity. Dendritic cells also interact with and influence the response of cells of the innate immune system. The manner in which dendritic cells influence the responses in cells of both the innate and adaptive immune systems has consequences for the bias of the adaptive response that mediates immunity to infection after vaccination or infection. It also provides an opportunity to intervene and to influence the response, allowing ways of developing appropriate vaccination strategies. Mouse and human studies have identified myeloid, lymphoid and plasmacytoid dendritic cells. Studies in domesticated animals with agents of specific infectious diseases have confirmed the applicability of certain of the generic models developed from mice or from in vitro studies on human cells. In vivo and ex vivo studies in cattle have demonstrated the existence of a number of subpopulations of myeloid dendritic cells. These cells differ in their ability to stimulate T cells and in the cytokines that they produce, observations clearly having important implications for the bias of the T-cell response. Dendritic cells also interact with the innate immune system, inducing responses that potentially bias the subsequent adaptive response.

scholarly journals Identification of HIV-Transmitting Sub-Epithelial Mononuclear Phagocytes in Human Anogenital and Colorectal Tissues

2020 ◽  
Author(s):  
Jake W Rhodes ◽  
Rachel A Botting ◽  
Kirstie M Bertram ◽  
Hafsa Rana ◽  
Heeva Baharlou ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune System ◽  
Target Cell ◽  
Cd4 T Cells ◽  
Pathogen Detection ◽  
Hiv Transmission ◽  
Sexual Transmission ◽  
Mononuclear Phagocytes ◽  
Microbicide Development

AbstractTissue mononuclear phagocytes (MNP) are specialised in pathogen detection and antigen presentation. They are the first cells of the immune system to encounter HIV and play a key role in transmission as they deliver the virus to CD4 T cells, which are the primary HIV target cell in which the virus undergoes replication. Most studies have investigated the role that epithelial MNPs play in HIV transmission but, as mucosal trauma and inflammation are strongly associated with HIV transmission, it is also important to examine the role that sub-epithelial MNPs play. Sub-epithelial MNPs are present in a diverse array of subsets which differ in their function and the pathogens they detect. Understanding how specific subsets interact with HIV and deliver the virus to CD4 T cells is therefore of key importance to vaccine and microbicide development. In this study we have shown that, after topical application, HIV can penetrate to interact with sub-epithelial resident myeloid cells in anogenital explants and defined the full array of MNP subsets that are present in all the human anogenital and colorectal sub-epithelial tissues that HIV may encounter during sexual transmission. In doing so we have identified two subsets that preferentially take up HIV, become infected and transmit the virus to CD4 T cells; CD14+CD1c+CD11c+ monocyte-derived dendritic cells and langerin-expressing dendritic cells 2 (DC2).

Elucidating Molecular Mechanisms of Cross-Presentation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2217-2217
Author(s):  
Shin-Rong Julia Wu
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune System ◽  
Molecular Mechanisms ◽  
Conflicts Of Interest ◽  
Activation Markers ◽  
Mhc I ◽  
Cross Presentation ◽  
Intact Immune System

The immune system regulates many processes vital to homeostasis. Antigen cross-presentation, an immune process specific to dendritic cells (DCs), critically contributes to maintaining homeostasis by regulating immune tolerance, antiviral activity, and antitumor responses. Through cross-presentation, extracellular antigen is processed and presented by MHC I on DCs to CD8 T cells. Despite cross-presentation's crucial role in mediating immune responses, its molecular regulation remains poorly defined. A potential breakthrough came when, using an in vitro shRNA-mediated knockdown (KD) approach, a group identified Sec22b as a central regulatory molecule of the pathway1. They demonstrated that Sec22b mediates recruitment of proteins necessary for MHC I-antigen loading from the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) to the antigen-containing phagosome, promoting cross-presentation. Thus, we tested the hypothesis that Sec22b mediates cross-presentation in vivo, in the context of an intact immune system under physiological conditions. We generated DC-specific Sec22b knockout (KO) mice (CD11cCre Sec22bfl/fl) from Sec22b-conditional gene trapped founder mice. These mice develop normally and have an intact immune system. KO DCs from spleen and bone marrow (BM) have Cre-mediated excision at the Sec22b locus, verified by PCR, and reduction of Sec22b production, verified by Western Blot. KO DCs from spleen and BM express activation markers in response to TLR and NLR stimulation at comparable levels to Cre- Sec22bfl/fl (FL) mice. By adoptively transferring ovalbumin (OVA)-specific (OT-I) T cells into these mice, then injecting with soluble OVA i.p., we measured OT-I T cell proliferation as a readout of cross-presentation. To our surprise, we saw no difference in the ability of KO versus FL mice to cross-present OVA (p >0.9). This observation was verified with in vitro assays with KO DCs from BM and spleen cross-presenting soluble OVA (0-3 mg/mL). We obtained similar findings using bead-bound, insoluble OVA. From this, we concluded Sec22b is not necessary for cross-presentation, invalidating our hypothesis. We were, however, able to reduce cross-presentation by shRNA-mediated KD of Sec22b (p <0.05), reproducing published observations. This discrepancy in observations was not due to functional compensation in KO BMDCs by Sec22b homologs, Sec22a or Sec22c, which we determined using qPCR. Intriguingly, when we treated KO BMDCs with the Sec22b-targeting shRNA, we again observed a reduction in cross-presentation (p <0.05). The reduction was comparable to that found in Sec22b-targeting shRNA-treated FL and WT BMDCs. Taken together, our data (a) demonstrate that Sec22b is not necessary for cross-presentation, (b) suggest the existence of a novel critical mediator of cross-presentation that is also targeted by the shRNA sequence used and (c) caution against extrapolating mechanisms or phenotypes based on KD studies alone. Cebrian, I. et al. Sec22b regulates phagosomal maturation and antigen crosspresentation by dendritic cells. Cell147, 1355-1368 (2011). Disclosures No relevant conflicts of interest to declare.

scholarly journals Immune mechanisms in arterial hypertension. Recent advances

2021 ◽  
Author(s):  
Ulrich O. Wenzel ◽  
Heimo Ehmke ◽  
Marlies Bode
Keyword(s):  
Blood Pressure ◽  
T Cells ◽  
Dendritic Cells ◽  
Immune System ◽  
Organ Damage ◽  
T Cell Subsets ◽  
Blood Pressure Elevation ◽  
End Organ Damage ◽  
Pressure Elevation ◽  
Recent Advances

AbstractIncreasing evidence indicates that hypertension and hypertensive end-organ damage are not only mediated by hemodynamic injury. Inflammation also plays an important role in the pathophysiology and contributes to the deleterious consequences of this disease. Cells of the innate immune system including monocyte/macrophages and dendritic cells can promote blood pressure elevation via effects mostly on kidney and vascular function. Moreover, convincing evidence shows that T and B cells from the adaptive immune system are involved in hypertension and hypertensive end-organ damage. Skin monocyte/macrophages, regulatory T cells, natural killer T cells, and myeloid-derived suppressor cells have been shown to exert blood pressure controlling effects. Sodium intake is undoubtedly indispensable for normal body function but can be detrimental when taken in excess of dietary requirements. Sodium levels also modulate the function of monocyte/macrophages, dendritic cells, and different T cell subsets. Some of these effects are mediated by changes in the microbiome and metabolome that can be found after high salt intake. Modulation of the immune response can reduce severity of blood pressure elevation and hypertensive end-organ damage in several animal models. The purpose of this review is to briefly summarize recent advances in immunity and hypertension as well as hypertensive end-organ damage.

The patient with systemic lupus erythematosus

2015 ◽  
Author(s):  
Johan van der Vlag ◽  
Jo H. M. Berden
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Dendritic Cells ◽  
Immune System ◽  
B Cells ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Immune Complexes ◽  
Heparan Sulphate ◽  
Systemic Lupus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with various clinical manifestations. The hallmark of SLE is the presence of antibodies against nuclear constituents, such as double-stranded (ds)DNA, histones, and nucleosomes. Local deposition of antinuclear antibodies in complex with nuclear autoantigens induces serious inflammatory conditions that can affect several tissues and organs, including the kidney.The levels of antinucleosome and anti-dsDNA antibodies seem to correlate with glomerulonephritis and these autoantibodies can often be detected years before the patient is diagnosed with SLE. Apoptotic debris is present in the extracellular matrix and circulation of patients with SLE due to an aberrant process of apoptosis and/or insufficient clearance of apoptotic cells and apoptotic debris. The non-cleared apoptotic debris in patients with SLE may lead to activation of both the innate (myeloid and plasmacytoid dendritic cells) and adaptive (T and B cells) immune system. In addition to the activation by apoptotic debris and immune complexes, the immune system in SLE may be deregulated at the level of (a) presentation of self-peptides by antigen-presenting cells, (b) selection processes for both B and T cells, and (c) regulatory processes of B- and T-cell responses. Lupus nephritis may be classified in different classes based on histological findings in renal biopsies. The chromatin-containing immune complexes deposit in the capillary filter, most likely due to the interaction of chromatin with the polysaccharide heparan sulphate. A decreased renal expression of the endonuclease DNaseI further contributes to the glomerular persistence of chromatin and the development of glomerulonephritis.Current treatment of lupus nephritis is not specific and aims to reduce the inflammatory response with general immunosuppressive therapies. However, research has revealed novel potential therapeutic candidates at the level of dendritic cells, B cells, and T cells.

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