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Immunological tolerance

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https://www.readbyqxmd.com/read/28941880/alternative-theories-pregnancy-and-immune-tolerance
#1
Elizabeth A Bonney
For some time, reproductive immunologists have worked to understand the balance between maternal tolerance of the fetus, maternal health, and fetal protection which leads to successful pregnancy in mammalian species. We have always understood the potential importance of multiple factors, including nutrition, genetics, anatomy, hormonal regulation, environmental insult and many others. Yet, we still struggle to combine our knowledge of these factors and immunology to finally understand complex diseases of pregnancy, such as preeclampsia...
September 18, 2017: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/28941667/advances-and-highlights-in-allergen-immunotherapy-on-the-way-to-sustained-clinical-and-immunologic-tolerance
#2
Margot Berings, Cagatay Karaaslan, Can Altunbulakli, Philippe Gevaert, Mübeccel Akdis, Claus Bachert, Cezmi A Akdis
Allergen immunotherapy (AIT) is an effective treatment strategy for allergic diseases and has been used for more than 100 years. In recent years, however, the expectations on concepts, conduct, statistical evaluation and reporting have been significantly developed. Products have undergone dose-response and confirmative studies in adults and children to provide evidence for the optimal dosage, safety and efficacy of AIT vaccines using subcutaneous and sublingual delivery pathways in large patient cohorts, ensuring solid conclusions to be drawn from them for the advantage of patients and societies alike...
September 20, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28939389/recombinant-allergen-and-peptide-based-approaches-for-allergy-prevention-by-oral-tolerance
#3
REVIEW
Raffaela Campana, Huey-Jy Huang, Raphaela Freidl, Birgit Linhart, Susanne Vrtala, Thomas Wekerle, Alexander Karaulov, Rudolf Valenta
Several studies conducted in animal models for immunologically-mediated hypersensitivity diseases have shown that oral administration of antigens early in life can prevent the development of specific humoral and cellular immune responses and thus hypersensitivity reactions to the respective antigens. Such data were also obtained in models for Immunoglobulin E (IgE)-associated allergy, the most common hypersensitivity disease affecting more than 25% of the population. Based on data obtained in animal models for allergy several clinical intervention studies have been conducted in children to study if oral administration of materials containing allergens or allergen-derived peptides early in life can prevent the subsequent development of allergy...
September 19, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28939158/formulation-of-the-bivalent-prostate-cancer-vaccine-with-surgifoam-elicits-antigen-specific-effector-t-cells-in-psa-transgenic-mice
#4
Dev Karan
We previously developed and characterized an adenoviral-based prostate cancer vaccine for simultaneous targeting of prostate-specific antigen (PSA) and prostate stem cell antigen (PSCA). We also demonstrated that immunization of mice with the bivalent vaccine (Ad5-PSA+PSCA) inhibited the growth of established prostate tumors. However, there are multiple challenges hindering the success of immunological therapies in the clinic. One of the prime concerns has been to overcome the immunological tolerance and maintenance of long-term effector T cells...
September 19, 2017: Vaccine
https://www.readbyqxmd.com/read/28937406/tolerance-in-xenotransplantation
#5
Kazuhiko Yamada, Megan Sykes, David H Sachs
PURPOSE OF REVIEW: This review describes recent progress in tolerance-inducing strategies across xenogeneic immunological barriers as well as the potential benefit of a tolerance strategy for islets and kidney xenotransplantation. RECENT FINDINGS: Using advanced gene editing technologies, xenotransplantation from multitransgenic alpha-1,3-galactosyltransferase knockout pigs has demonstrated marked prolongation of renal xenograft survival, ranging from days to greater than several months for life-supporting kidneys, and more than 2 years in a heterotopic nonlife-supporting cardiac xenograft model...
September 20, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28932650/gene-editing-gene-therapy-and-cell-xenotransplantation-cell-transplantation-across-species
#6
REVIEW
Nizar I Mourad, Pierre Gianello
PURPOSE OF REVIEW: Cell xenotransplantation has the potential to provide a safe, ethically acceptable, unlimited source for cell replacement therapies. This review focuses on genetic modification strategies aimed to overcome remaining hurdles standing in the way of clinical porcine islet transplantation and to develop neural cell xenotransplantation. RECENT FINDINGS: In addition to previously described genetic modifications aimed to mitigate hyperacute rejection, instant blood-mediated inflammatory reaction, and cell-mediated rejection, new data showing the possibility of increasing porcine islet insulin secretion by transgenesis is an interesting addition to the array of genetically modified pigs available for xenotransplantation...
2017: Current Transplantation Reports
https://www.readbyqxmd.com/read/28932628/a-novel-in-silico-framework-to-improve-mhc-i-epitopes-and-break-the-tolerance-to-melanoma
#7
Cristian Capasso, Aniket Magarkar, Victor Cervera-Carascon, Manlio Fusciello, Sara Feola, Martin Muller, Mariangela Garofalo, Lukasz Kuryk, Siri Tähtinen, Lucio Pastore, Alex Bunker, Vincenzo Cerullo
Tolerance toward tumor antigens, which are shared by normal tissues, have often limited the efficacy of cancer vaccines. However, wild type epitopes can be tweaked to activate cross-reactive T-cell clones, resulting in antitumor activity. The design of these analogs (i.e., heteroclitic peptides) can be difficult and time-consuming since no automated in silico tools are available. Hereby we describe the development of an in silico framework to improve the selection of heteroclitic peptides. The Epitope Discovery and Improvement System (EDIS) was first validated by studying the model antigen SIINFEKL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28931462/paradoxical-development-of-polymyositis-like-autoimmunity-through-augmented-expression-of-autoimmune-regulator-aire
#8
Hitoshi Nishijima, Tatsuya Kajimoto, Yoshiki Matsuoka, Yasuhiro Mouri, Junko Morimoto, Minoru Matsumoto, Hiroshi Kawano, Yasuhiko Nishioka, Hisanori Uehara, Keisuke Izumi, Koichi Tsuneyama, Il-Mi Okazaki, Taku Okazaki, Kazuyoshi Hosomichi, Ayako Shiraki, Makoto Shibutani, Kunitoshi Mitsumori, Mitsuru Matsumoto
Autoimmunity is prevented by the function of the autoimmune regulator [AIRE (Aire in mice)], which promotes the expression of a wide variety of tissue-restricted antigens (TRAs) from medullary thymic epithelial cells (mTECs) and from a subset of peripheral antigen-presenting cells (APCs). We examined the effect of additive expression of human AIRE (huAIRE) in a model of autoimmune diabetes in NOD mice. Unexpectedly, we observed that mice expressing augmented AIRE/Aire developed muscle-specific autoimmunity associated with incomplete maturation of mTECs together with impaired expression of Aire-dependent TRAs...
September 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28930796/navigating-t-cell-immunometabolism-in-transplantation
#9
Naoki Tanimine, Laurence A Turka, Bhavana Priyadharshini
Recently, a new discipline termed "immunometabolism" has transformed the field of immunology. It encompasses the study of the intrinsic metabolic pathways of different immune subsets and their impact on cellular fate and function. For instance, broadly speaking, pro-inflammatory cells depend upon glycolysis and glutamine oxidation while cells involved in anti-inflammatory response such as Foxp3+ regulatory T cells (Tregs) utilize predominantly fatty acid oxidation. However, while a useful paradigm, this actually is a reductionist view and the engagement of these metabolic pathways is not mutually exclusive between these subsets...
September 19, 2017: Transplantation
https://www.readbyqxmd.com/read/28928833/disrupted-fibroblastic-reticular-cells-and-interleukin-7-expression-in-tumor-draining-lymph-nodes
#10
Jianbao Gao, Lintao Zhao, Lina Liu, Yang Yang, Bo Guo, Bo Zhu
The immune system of patients with cancer is usually in an inhibitory state. Lymph node (LN) draining of pathological sites provides a suitable microenvironment where adaptive immune responses mainly occur. However, the microenvironment in the tumor draining lymph nodes (TDLNs) of patients with cancer appears to be in favor of tolerance. The effects of tumor cells on TDLNs have not been elaborated clearly. The present results have indicated that tumor cells may directly affect TDLNs by decreasing the fibroblastic reticular cell population that led to less interleukin-7 secretion...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927305/discovery-and-application-of-immune-biomarkers-for-hematological-malignancies
#11
Dimitrios Zafeiris, Jayakumar Vadakekolathu, Sarah Wagner, Alan Graham Pockley, Graham Roy Ball, Sergio Rutella
Hematological malignancies originate and progress in primary and secondary lymphoid organs, where they establish a uniquely immune-suppressive tumour microenvironment. Although high-throughput transcriptomic and proteomic approaches are being employed to interrogate immune surveillance and escape mechanisms in patients with solid tumours, and to identify actionable targets for immunotherapy, our knowledge of the immunological landscape of hematological malignancies, as well as our understanding of the molecular circuits that underpin the establishment of immune tolerance, is not comprehensive...
September 25, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28926559/novelties-in-evaluation-and-monitoring-of-human-immunodeficiency-virus-1-infection-is-standard-virological-suppression-enough-for-measuring-antiretroviral-treatment-success
#12
Valentina Svicher, Giulia Marchetti, Adrianna Ammassari, Francesca Ceccherini-Silberstein, Loredana Sarmati
The high potency and tolerability of the currently available antiretroviral drugs has modified HIV-1 infection from a life-threatening disease to a chronic illness. Nevertheless, some issues still remain open to optimize the management of HIV-1 infected patients in term of maintenance of virological suppression over time, identifying patients that could benefit from simplification therapy, and reducing co-mordibities driven by chronic inflammation. The availability of robust and affordable virological and immunological markers can help in solving these issues by providing information on the burden of HIV-1 reservoir in all the anatomical compartments in which the virus replicates as well as on persistent inflammation, immune activation and senescence despite successful virological suppression...
September 19, 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28923762/translating-basic-research-into-clinical-practice-vitamin-d-in-asthma-mechanisms-of-action-and-considerations-for-clinical-trials
#13
REVIEW
Paul E Pfeffer, Catherine M Hawrylowicz
There is increasing interest in the therapeutic utility of vitamin D in asthma, supported by a significant body of evidence on epidemiological associations between vitamin D insufficiency and worse asthma control. In support of a causal relationship, vitamin D beneficially modulates diverse immunological pathways in heterogeneous asthma endotypes, regulating the actions of lymphocytes, mast cells, antigen-presenting cells and structural cells to dampen excessive inflammatory responses. Allergic asthma is characterised by a failure of immune tolerance, and development of pathological responses to inhaled aeroallergens, and vitamin D has been extensively shown to support immune regulation...
September 15, 2017: Chest
https://www.readbyqxmd.com/read/28923633/changes-in-dna-methylation-of-glucocorticoid-induced-tumor-necrosis-factor-receptor-and-its-ligand-in-liver-transplantation
#14
W Wang, G Ji, Y Chen, J Wang, J Sun, G Tang, Z Xie, H Zhao, G Liu, S Tan, G Chen, H Xue
Liver transplantation (LT) is the criterion standard of care in patients with end-stage liver disease and those with tumors of hepatic origin in the setting of liver dysfunction. Chronic immune rejection of the liver transplant can lead to bad prognosis for patients. Glucocorticoid-induced tumor necrosis factor receptor (GITR) play a key role in dominant immunologic self-tolerance maintained by CD25+/CD4+ regulatory T cells. Here, we investigated the DNA methylation variations of GITR and GITR ligand (GITRL) using pyrosequencing by analyzing blood DNA samples of patients after LT...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28921585/allergooncology-opposite-outcomes-of-immune-tolerance-in-allergy-and-cancer
#15
E Jensen-Jarolim, H J Bax, R Bianchini, S Crescioli, T R Daniels-Wells, D Dombrowicz, E Fiebiger, H J Gould, S Irshad, J Janda, D H Josephs, F Levi-Schaffer, L O Mahony, G Pellizzari, M L Penichet, F Redegeld, F Roth-Walter, J Singer, E Untersmayr, L Vangelista, S N Karagiannis
While desired for the cure of allergy, regulatory immune cell subsets and non-classical Th2-biased inflammatory mediators in the tumour microenvironment can contribute to immune suppression and escape of tumours from immunological detection and clearance. A key aim in the cancer field is therefore to design interventions that can break immunological tolerance and halt cancer progression, whereas on the contrary allergen immunotherapy exactly aims to induce tolerance. In this position paper, we review insights on immune tolerance derived from allergy and from cancer inflammation, focusing on what is known about the roles of key immune cells and mediators...
September 16, 2017: Allergy
https://www.readbyqxmd.com/read/28921501/immunological-tolerance-to-lcmv-antigens-differently-affects-control-of-acute-and-chronic-virus-infection-in-mice
#16
Christina Woopen, Tobias Straub, Oliver Schweier, Ulrike Aichele, Katharina Düker, Thomas Boehm, Hanspeter Pircher
Cytotoxic T lymphocytes (CTLs) play a key role in the control of lymphocytic choriomeningitis virus (LCMV) infection. In C57BL/6 mice (H-2(b) ), the CTL response is mainly directed against epitopes from the LCMV glycoprotein (GP) and the nucleoprotein (NP) which represent the two major viral proteins. The role of GP- versus NP-derived epitopes for viral clearance was examined using transgenic (tg) mice ubiquitously expressing LCMV GP and NP, respectively. These mice lack GP- or NP-specific CTLs and show decreased levels of GP- or NP-specific antibodies as a result of tolerance induction...
August 11, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28918995/cutaneous-adverse-events-of-targeted-therapies-for-hematolymphoid-malignancies
#17
REVIEW
Julia D Ransohoff, Bernice Y Kwong
The identification of oncogenic drivers of liquid tumors has led to the rapid development of targeted agents with distinct cutaneous adverse event (AE) profiles. The diagnosis and management of these skin toxicities has motivated a novel partnership between dermatologists and oncologists in developing supportive oncodermatology clinics. In this article we review the current state of knowledge of clinical presentation, mechanisms, and management of the most common and significant cutaneous AEs observed during treatment with targeted therapies for hematologic and lymphoid malignancies...
July 14, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28901417/discrimination-of-the-heterogeneity-of-bone-marrow%C3%A2-derived-dendritic-cells
#18
Jing Wang, Xiaomin Dai, Chiaching Hsu, Changsheng Ming, Ying He, Ji Zhang, Lai Wei, Ping Zhou, Cong-Yi Wang, Jun Yang, Nianqiao Gong
The present study aimed to discriminate different subsets of cultured dendritic cells (DCs) to evaluate their immunological characteristics. DCs offer an important foundation for immunological studies, and mouse bone marrow (BM) cells cultured with granulocyte‑macrophage colony‑stimulating factor (GM‑CSF) have been used extensively to generate CD11c+/major histocompatibility complex II+ BM‑derived DCs (BMDCs). Immature DCs are considered to have strong migration and phagocytic antigen‑capturing abilities, whereas mature DCs are thought to activate naive T cells and express high levels of costimulatory cytokines and adhesion molecules...
September 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900679/ctla-4-an-essential-immune-checkpoint-for-t-cell-activation
#19
Shunsuke Chikuma
The response of peripheral T lymphocytes (T cell) is controlled by multiple checkpoints to avoid unwanted activation against self-tissues. Two opposing costimulatory receptors, CD28 and CTLA-4, on T cells bind to the same ligands (CD80 and CD86) on antigen-presenting cells (APCs), and provide positive and negative feedback for T-cell activation, respectively. Early studies suggested that CTLA-4 is induced on activated T cells and binds to CD80/CD86 with much stronger affinity than CD28, providing a competitive inhibition...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28900678/socs1-regulator-of-t-cells-in-autoimmunity-and-cancer
#20
Subburaj Ilangumaran, Diwakar Bobbala, Sheela Ramanathan
SOCS1 is a negative feedback regulator of cytokine and growth factor receptor signaling, and plays an indispensable role in attenuating interferon gamma signaling. Studies on SOCS1-deficient mice have established a crucial role for SOCS1 in regulating CD8(+) T cell homeostasis. In the thymus, SOCS1 prevents thymocytes that had failed positive selection from surviving and expanding, ensures negative selection and prevents inappropriate developmental skewing toward the CD8 lineage. In the periphery, SOCS1 not only controls production of T cell stimulatory cytokines but also attenuates the sensitivity of CD8(+) T cells to synergistic cytokine stimulation and antigen non-specific activation...
September 13, 2017: Current Topics in Microbiology and Immunology
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