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Immunological tolerance

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https://www.readbyqxmd.com/read/28630212/a-pilot-study-of-stereotactic-body-radiation-therapy-combined-with-cytoreductive-nephrectomy-for-metastatic-renal-cell-carcinoma
#1
Anurag K Singh, Timothy B Winslow, Mohammad Habiby Kermany, Vincent Goritz, Lilia Heit, Austin Miller, Nicholas C Hoffend, Leighton C Stein, Lalith Kumaraswamy, Graham W Warren, Wiam Bshara, Kunle Odunsi, Junko Matsuzaki, Scott I Abrams, Thomas Schwaab, Jason B Muhitch
<p>While stereotactic body radiation therapy (SBRT) can reduce tumor volumes in metastatic renal cell carcinoma (mRCC) patients, little is known regarding the immunomodulatory effects of high-dose radiation in the tumor microenvironment. The main objectives of this pilot study were to assess the safety and feasibility of nephrectomy following SBRT treatment of mRCC patients and analyze the immunological impact of high-dose radiation.</p> <br /><br />Experimental Design: Human RCC cell lines were irradiated and evaluated for immunomodulation...
June 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28627520/unique-aspects-of-the-perinatal-immune-system
#2
REVIEW
Xiaoming Zhang, Dania Zhivaki, Richard Lo-Man
The early stages of life are associated with increased susceptibility to infection, which is in part due to an ineffective immune system. In the context of infection, the immune system must be stimulated to provide efficient protection while avoiding insufficient or excessive activation. Yet, in early life, age-dependent immune regulation at molecular and cellular levels contributes to a reduced immunological fitness in terms of pathogen clearance and response to vaccines. To enable microbial colonization to be tolerated at birth, epigenetic immune cell programming and early life-specific immune regulatory and effector mechanisms ensure that vital functions and organ development are supported and that tissue damage is avoided...
June 19, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28625830/bioengineering-strategies-for-inducing-tolerance-in-autoimmune-diabetes
#3
Steinunn Baekkeskov, Jeffrey A Hubbell, Edward A Phelps
Type 1 diabetes is an autoimmune disease marked by the destruction of insulin-producing beta cells in the pancreatic islets. Strategies to delay onset or prevent the autoimmune recognition of beta cell antigens or T cell-mediated killing of beta cells have mainly focused on systemic immunomodulation and antigen-specific immunotherapy. To bridge the fields of type 1 diabetes immunology and biomaterials engineering, this article will review recent trends in the etiology of type 1 diabetes immunopathology and will focus on the contributions of emerging bioengineered strategies in the fight against beta cell autoimmunity in type 1 diabetes...
June 15, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28623375/skin-immunity
#4
REVIEW
Agata Matejuk
Skin is the largest organ of the body with a complex network of multitude of cell types that perform plastic and dynamic cellular communication to maintain several vital processes such as inflammation, immune response including induction of tolerance and disease prevention, wound healing, and angiogenesis. Of paramount importance are immunological functions of the skin that protect from harmful exposure coming from external and internal environments. Awareness of skin immunity can provide a better comprehension of inflammation, autoimmunity, cancer, graft-versus-host disease, vaccination, and immunotherapy approaches...
June 16, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28621766/autologous-haematopoietic-stem-cell-transplantation-for-treatment-of-multiple-sclerosis
#5
REVIEW
Paolo A Muraro, Roland Martin, Giovanni Luigi Mancardi, Richard Nicholas, Maria Pia Sormani, Riccardo Saccardi
Autologous haematopoietic stem cell transplantation (AHSCT) is a multistep procedure that enables destruction of the immune system and its reconstitution from haematopoietic stem cells. Originally developed for the treatment of haematological malignancies, the procedure has been adapted for the treatment of severe immune-mediated disorders. Results from ∼20 years of research make a compelling case for selective use of AHSCT in patients with highly active multiple sclerosis (MS), and for controlled trials...
June 16, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28620098/cytokine-signaling-in-the-development-and-homeostasis-of-regulatory-t-cells
#6
Kevin H Toomer, Thomas R Malek
Cytokine signaling is indispensable for regulatory T-cell (Treg) development in the thymus, and also influences the homeostasis, phenotypic diversity, and function of Tregs in the periphery. Because Tregs are required for establishment and maintenance of immunological self-tolerance, investigating the role of cytokines in Treg biology carries therapeutic potential in the context of autoimmune disease. This review discusses the potent and diverse influences of interleukin (IL)-2 signaling on the Treg compartment, an area of knowledge that has led to the use of low-dose IL-2 as a therapy to reregulate autoaggressive immune responses...
June 15, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28611473/apc-targeted-proinsulin-expression-inactivates-insulin-specific-memory-cd8-t-cells-in-nod-mice
#7
Peta Ls Reeves, Rajeev Rudraraju, Xiao Liu, F Susan Wong, Emma E Hamilton-Williams, Raymond J Steptoe
Type 1 diabetes (T1D) results from T-cell mediated autoimmune destruction of pancreatic β cells. Effector T-cell responses emerge early in disease development and expand as disease progresses. Following β cell destruction, a long-lived T-cell memory is generated that represents a barrier to islet transplantation and other cellular insulin-replacement therapies. Development of effective immunotherapies that control or ablate β cell destructive effector and memory T cell responses has the potential to prevent disease progression and recurrence...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28608637/regulatory-t-cell-therapy-in-liver-transplantation
#8
REVIEW
Gavin P Whitehouse, Andrew Hope, Alberto Sanchez-Fueyo
Modern immunosuppression drug regimens have produced excellent short term survival after liver transplantation but it is generally accepted that the side effects of these medications remain a significant contributing factor for less satisfactory long term outcomes. The liver has unique tolerogenic properties as evidenced by the higher rates of operational tolerance seen in liver transplant recipients compared to other solid organ transplants and therefore liver transplantation offers an attractive setting in which to study tolerising therapies...
June 13, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28607488/stability-and-function-of-regulatory-t-cells-expressing-the-transcription-factor-t-bet
#9
Andrew G Levine, Alejandra Medoza, Saskia Hemmers, Bruno Moltedo, Rachel E Niec, Michail Schizas, Beatrice E Hoyos, Ekaterina V Putintseva, Ashutosh Chaudhry, Stanislav Dikiy, Sho Fujisawa, Dmitriy M Chudakov, Piper M Treuting, Alexander Y Rudensky
Adaptive immune responses are tailored to different types of pathogens through differentiation of naive CD4 T cells into functionally distinct subsets of effector T cells (T helper 1 (TH1), TH2, and TH17) defined by expression of the key transcription factors T-bet, GATA3, and RORγt, respectively. Regulatory T (Treg) cells comprise a distinct anti-inflammatory lineage specified by the X-linked transcription factor Foxp3 (refs 2, 3). Paradoxically, some activated Treg cells express the aforementioned effector CD4 T cell transcription factors, which have been suggested to provide Treg cells with enhanced suppressive capacity...
June 15, 2017: Nature
https://www.readbyqxmd.com/read/28606591/safety-and-immunogenicity-of-the-rvsv%C3%A2-g-zebov-gp-ebola-virus-vaccine-candidate-in-healthy-adults-a-phase-1b-randomised-multicentre-double-blind-placebo-controlled-dose-response-study
#10
D Gray Heppner, Tracy L Kemp, Brian K Martin, William J Ramsey, Richard Nichols, Emily J Dasen, Charles J Link, Rituparna Das, Zhi Jin Xu, Eric A Sheldon, Teresa A Nowak, Thomas P Monath
BACKGROUND: The 2014 Zaire Ebola virus outbreak highlighted the need for a safe, effective vaccine with a rapid onset of protection. We report the safety and immunogenicity of the recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSV∆G-ZEBOV-GP) across a 6 log10 dose range in two sequential cohorts. METHODS: In this phase 1b double-blind, placebo-controlled, dose-response study we enrolled and randomly assigned healthy adults (aged 18-61 years) at eight study sites in the USA to receive a single injection of vaccine or placebo, administered by intramuscular injection...
June 9, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28605294/safety-and-long-term-immunological-effects-of-cryj2-lamp-plasmid-vaccine-in-japanese-red-cedar-atopic-subjects-a-phase-i-study
#11
Yan Su, Eliezer Romeu-Bonilla, Athanasia Anagnostou, David Fitz-Patrick, William Hearl, Teri Heiland
Japanese Red Cedar (JRC) pollen induced allergy affects one third of Japanese and the development of effective therapies remains an unachieved challenge. We designed a DNA vaccine encoding CryJ2 allergen from the JRC pollen and Lysosomal Associated Membrane Protein 1 (LAMP-1) to treat JRC allergy. These Phase IA and IB trials assessed safety and immunological effects of the investigational CryJ2-LAMP DNA vaccine in both non-sensitive and sensitive Japanese expatriates living in Honolulu, Hawaii. In the Phase IA trial, six JRC non-sensitive subjects and nine JRC and/or Mountain Cedar (MC) sensitive subjects were given four vaccine doses (each 4 mg/1 ml) intramuscularly (IM) at 14-day intervals...
June 12, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28604556/immunologic-response-elicited-in-breast-cancer-patients-receiving-a-neugcgm3-based-vaccine-as-adjuvant-therapy
#12
Anet Valdes-Zayas, Zuyen Gonzalez, Vladimir Mulens, Aliz M Vega, Kirenia Perez, Patricia Lorenzo-Luaces, Maria C Rubio, Anabely Estevez, Idelmis Curbelo, Luis E Fernandez, Tania Crombet, Zaima Mazorra
This study aimed to investigate the immunogenicity of a cancer vaccine consisting of the NeuGcGM3 ganglioside combined with the outer membrane protein complex of Neisseria meningitides to form very small size particles. The vaccine is administered together with Montanide ISA51, as adjuvant treatment for breast cancer patients. After surgical resection and standard first-line chemo/radiotherapy, breast cancer patients in stage II-III were enrolled in a phase III clinical trial and allocated into 2 strata, according to the number of positive lymph nodes [stratum I (0-3); stratum II (≥4)]...
June 9, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28604446/evolving-approaches-in-the-identification-of-allograft-reactive-t-and-b-cells-in-mice-and-humans
#13
James S Young, Christine McIntosh, Maria-Luisa Alegre, Anita S Chong
Whether a transplanted allograft is stably accepted, rejected or achieves immunological tolerance is dependent on the frequency and function of alloreactive lymphocytes, making the identification and analysis of alloreactive T and B cells in transplant recipients critical for understanding mechanisms, and the prediction of allograft outcome. In animal models, tracking the fate of graft-reactive T and B cells allows investigators to uncover their biology and develop new therapeutic strategies to protect the graft...
June 8, 2017: Transplantation
https://www.readbyqxmd.com/read/28603089/specific-allergen-immunotherapy-for-the-treatment-of-allergic-asthma-a-review-of-current-evidence
#14
J Dominguez-Ortega, J Delgado, C Blanco, L Prieto, E Arroabarren, M Cimarra, A Henriquez-Santana, J Iglesias-Souto, J M Vega-Chicote, A I Tabar
Asthma is frequently associated with atopy, characterized by the production of specific immunoglobulin E in response to environmental allergens. Currently, two types of allergen immunotherapy (AIT) are used in clinical practice: subcutaneous and sublingual immunotherapy, both accepted as key components of the therapeutic repertoire for allergic rhinitis and conjunctivitis. However, their role in asthma remains controversial. The present document is aimed at providing the clinicians with a review of the evidence on the use of AIT in asthma, focusing on the most relevant aspects of its mechanism of action, its efficacy, and existing data on safety, tolerability, and cost-effectivity, both in pediatric and adult populations...
June 2017: Journal of Investigational Allergology & Clinical Immunology
https://www.readbyqxmd.com/read/28593827/liposome-based-immunotherapy-against-autoimmune-diseases-therapeutic-effect-on-multiple-sclerosis
#15
Irma Pujol-Autonell, Maria-Jose Mansilla, Silvia Rodriguez-Fernandez, Mary Cano-Sarabia, Juan Navarro-Barriuso, Rosa-Maria Ampudia, Aleix Rius, Sonia Garcia-Jimeno, David Perna-Barrull, Eva Martinez-Caceres, Daniel Maspoch, Marta Vives-Pi
AIM: Based on the ability of apoptosis to induce immunological tolerance, liposomes were generated mimicking apoptotic cells, and they arrest autoimmunity in Type 1 diabetes. Our aim was to validate the immunotherapy in other autoimmune disease: multiple sclerosis. MATERIALS & METHODS: Phosphatidylserine-rich liposomes were loaded with disease-specific autoantigen. Therapeutic capability of liposomes was assessed in vitro and in vivo. RESULTS: Liposomes induced a tolerogenic phenotype in dendritic cells, and arrested autoimmunity, thus decreasing the incidence, delaying the onset and reducing the severity of experimental disease, correlating with an increase in a probably regulatory CD25(+) FoxP3(-) CD4(+) T-cell subset...
June 2017: Nanomedicine
https://www.readbyqxmd.com/read/28590313/current-management-of-metastatic-renal-cell-carcinoma-evolving-new-therapies
#16
Ravi Kumar, Anil Kapoor
PURPOSE OF REVIEW: Targeted therapies have recently replaced cytokine treatments as the gold standard for management of metastatic renal cell carcinoma (mRCC). Currently approved treatments include the tyrosine kinase inhibitors sunitinib, pazopanib, axitinib, sorafenib, cabozantinib and lenvatinib; the vascular endothelial growth factor (VEGF) inhibitor bevacizumab; the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus; and the immunologic nivolumab. The purpose of this review is to provide an updated analysis of the clinical data supporting the use of these agents in the first-line and second-line setting...
June 5, 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28588142/recent-evolution-of-extreme-cestode-growth-suppression-by-a-vertebrate-host
#17
Jesse N Weber, Natalie C Steinel, Kum Chuan Shim, Daniel I Bolnick
Parasites can be a major cause of natural selection on hosts, which consequently evolve a variety of strategies to avoid, eliminate, or tolerate infection. When ecologically similar host populations present disparate infection loads, this natural variation can reveal immunological strategies underlying adaptation to infection and population divergence. For instance, the tapeworm Schistocephalus solidus persistently infects 0-80% of threespine stickleback (Gasterosteus aculeatus) in lakes on Vancouver Island...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28585775/the-roles-of-the-pd-1-pd-l1-pathway-at-immunologically-privileged-sites
#18
Li-Ling Wang, Zhi-Hui Li, Xiao-Hui Hu, Kahinho P Muyayalo, Yong-Hong Zhang, Ai-Hua Liao
The PD-1/PD-L1 pathway plays a vital role in the maintenance of peripheral tolerance, promoting the development and function of regulatory T cells, and maintaining the quiescence of autoreactive T cells. Abnormalities in this inhibitory pathway are involved in the pathogenesis of some disorders such as tumours, autoimmune diseases, pregnancy complications, and transplantation rejection. Immune privilege represents a special immunological condition, where foreign antigens can be tolerated and do not elicit an immune response...
June 6, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28579800/meat-and-nicotinamide-a-causal-role-in-human-evolution-history-and-demographics
#19
REVIEW
Adrian C Williams, Lisa J Hill
Hunting for meat was a critical step in all animal and human evolution. A key brain-trophic element in meat is vitamin B3 / nicotinamide. The supply of meat and nicotinamide steadily increased from the Cambrian origin of animal predators ratcheting ever larger brains. This culminated in the 3-million-year evolution of Homo sapiens and our overall demographic success. We view human evolution, recent history, and agricultural and demographic transitions in the light of meat and nicotinamide intake. A biochemical and immunological switch is highlighted that affects fertility in the 'de novo' tryptophan-to-kynurenine-nicotinamide 'immune tolerance' pathway...
2017: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/28579319/immunological-functions-of-the-omentum
#20
REVIEW
Selene Meza-Perez, Troy D Randall
The omentum is a visceral adipose tissue with unique immune functions. Although it is primarily an adipose tissue, the omentum also contains lymphoid aggregates, called milky spots (MSs), that contribute to peritoneal immunity by collecting antigens, particulates, and pathogens from the peritoneal cavity and, depending on the stimuli, promoting a variety of immune responses, including inflammation, tolerance, or even fibrosis. Reciprocal interactions between cells in the MS and adipocytes regulate their immune and metabolic functions...
April 6, 2017: Trends in Immunology
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