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Immune tolerance

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https://www.readbyqxmd.com/read/28239677/the-discontinuity-theory-of-immunity
#1
Thomas Pradeu, Eric Vivier
Some biological systems detect the rate of change in a stimulus rather than the stimulus itself only. We suggest that the immune system works in this way. According to the discontinuity theory of immunity, the immune system responds to sudden changes in antigenic stimulation and is rendered tolerant by slow or continuous stimulation. This basic principle, which is supported by recent data on immune checkpoints in viral infections, cancers, and allergies, can be seen as a unifying framework for diverse immune responses...
July 14, 2016: Science Immunology
https://www.readbyqxmd.com/read/28239465/pd-1-blockade-induces-remissions-in-relapsed-classical-hodgkin-lymphoma-following-allogeneic-hematopoietic-stem-cell-transplantation
#2
James Godfrey, Michael R Bishop, Sahr Syed, Elizabeth Hyjek, Justin Kline
BACKGROUND: Allogeneic hematopoietic stem cell transplantation and checkpoint blockade therapy are immune-based therapies that have activity in selected refractory hematologic malignancies. Interest has developed in combining these treatments for high-risk hematologic diseases. However, there is concern that checkpoint blockade could augment graft-versus-host disease, and very few studies have evaluated the safety of checkpoint blockade in the post-allogeneic setting. Here, we report the outcomes of three patients with relapsed classical Hodgkin's lymphoma following allogeneic transplant that were treated with the anti-PD-1 antibody, nivolumab...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28239462/thrombocytopenia-in-patients-with-melanoma-receiving-immune-checkpoint-inhibitor-therapy
#3
Eileen Shiuan, Kathryn E Beckermann, Alpaslan Ozgun, Ciara Kelly, Meredith McKean, Jennifer McQuade, Mary Ann Thompson, Igor Puzanov, John P Greer, Suthee Rapisuwon, Michael Postow, Michael A Davies, Zeynep Eroglu, Douglas Johnson
BACKGROUND: Immune checkpoint inhibitors, including antibodies against programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), are being used with increasing frequency for the treatment of cancer. Immune-related adverse events (irAEs) including colitis, dermatitis, and pneumonitis are well described, but less frequent events are now emerging with larger numbers of patients treated. Herein we describe the incidence and spectrum of thrombocytopenia following immune checkpoint inhibitor therapy and two severe cases of idiopathic thrombocytopenic purpura (ITP)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28239383/effects-of-cigarette-smoking-on-transplant-survival-extending-or-shortening-it
#4
Feifei Qiu, Ping Fan, Golay D Nie, Huazhen Liu, Chun-Ling Liang, Wanlin Yu, Zhenhua Dai
Cigarette smoking (CS) regulates both innate and adaptive immunity and causes numerous diseases, including cardiovascular, respiratory, and autoimmune diseases, allergies, cancers, and transplant rejection. Therefore, smoking poses a serious challenge to the healthcare system worldwide. Epidemiological studies have always shown that CS is one of the major risk factors for transplant rejection, even though smoking plays redundant roles in regulating immune responses. The complex roles for smoking in immunoregulation are likely due to molecular and functional diversities of cigarette smoke components, including carbon monoxide (CO) and nicotine...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28239381/presentation-of-autoantigen-in-peripheral-lymph-nodes-is-sufficient-for-priming-autoreactive-cd8-t-cells
#5
Nadine Honke, Namir Shaabani, John R Teijaro, Urs Christen, Cornelia Hardt, Judith Bezgovsek, Philipp A Lang, Karl S Lang
Peripheral tolerance is an important mechanism by which the immune system can guarantee a second line of defense against autoreactive T and B cells. One autoimmune disease that is related to a break of peripheral tolerance is diabetes mellitus type 1. Using the RIP-GP mouse model, we analyzed the role of the spleen and lymph nodes (LNs) in priming CD8(+) T cells and breaking peripheral tolerance. We found that diabetes developed in splenectomized mice infected with the lymphocytic choriomeningitis virus (LCMV), a finding showing that the spleen was not necessary in generating autoimmunity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28238601/safety-immunogenicity-and-preliminary-clinical-efficacy-of-a-vaccine-against-extraintestinal-pathogenic-escherichia-coli-in-women-with-a-history-of-recurrent-urinary-tract-infection-a-randomised-single-blind-placebo-controlled-phase-1b-trial
#6
Angela Huttner, Christoph Hatz, Germie van den Dobbelsteen, Darren Abbanat, Alena Hornacek, Rahel Frölich, Anita M Dreyer, Patricia Martin, Todd Davies, Kellen Fae, Ingrid van den Nieuwenhof, Stefan Thoelen, Serge de Vallière, Anette Kuhn, Enos Bernasconi, Volker Viereck, Tilemachos Kavvadias, Kerstin Kling, Gloria Ryu, Tanja Hülder, Sabine Gröger, David Scheiner, Cristina Alaimo, Stephan Harbarth, Jan Poolman, Veronica Gambillara Fonck
BACKGROUND: Escherichia coli infections are increasing worldwide in community and hospital settings. The E coli O-antigen is a promising vaccine target. We aimed to assess the safety and immunogenicity of a bioconjugate vaccine containing the O-antigens of four E coli serotypes (ExPEC4V). METHODS: In this multicentre phase 1b, first-in-human, single-blind, placebo-controlled trial, we randomly assigned (1:1) healthy adult women with a history of recurrent urinary tract infection (UTI) to receive a single injection of either intramuscular ExPEC4V or placebo...
February 23, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28238174/combining-talimogene-laherparepvec-with-immunotherapies-in-melanoma-and-other-solid-tumors
#7
REVIEW
Reinhard Dummer, Christoph Hoeller, Isabella Pezzani Gruter, Olivier Michielin
Talimogene laherparepvec is a first-in-class intralesional oncolytic immunotherapy. In a recent Phase III trial (OPTiM), talimogene laherparepvec significantly improved durable response rate compared with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF). Overall response rate was also higher in the talimogene laherparepvec arm, and the greatest efficacy was demonstrated in patients with earlier-stage (IIIB, IIIC, or IVM1a) melanoma. Talimogene laherparepvec was well tolerated, with the majority (89%) of adverse events being grade 1 or 2...
February 25, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28237839/systemic-aav8-mediated-gene-therapy-drives-whole-body-correction-of-myotubular-myopathy-in-dogs
#8
David L Mack, Karine Poulard, Melissa A Goddard, Virginie Latournerie, Jessica M Snyder, Robert W Grange, Matthew R Elverman, Jérôme Denard, Philippe Veron, Laurine Buscara, Christine Le Bec, Jean-Yves Hogrel, Annie G Brezovec, Hui Meng, Lin Yang, Fujun Liu, Michael O'Callaghan, Nikhil Gopal, Valerie E Kelly, Barbara K Smith, Jennifer L Strande, Fulvio Mavilio, Alan H Beggs, Federico Mingozzi, Michael W Lawlor, Ana Buj-Bello, Martin K Childers
X-linked myotubular myopathy (XLMTM) results from MTM1 gene mutations and myotubularin deficiency. Most XLMTM patients develop severe muscle weakness leading to respiratory failure and death, typically within 2 years of age. Our objective was to evaluate the efficacy and safety of systemic gene therapy in the p.N155K canine model of XLMTM by performing a dose escalation study. A recombinant adeno-associated virus serotype 8 (rAAV8) vector expressing canine myotubularin (cMTM1) under the muscle-specific desmin promoter (rAAV8-cMTM1) was administered by simple peripheral venous infusion in XLMTM dogs at 10 weeks of age, when signs of the disease are already present...
February 22, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28237837/a-novel-dna-vaccine-platform-enhances-neo-antigen-like-t-cell-responses-against-wt1-to-break-tolerance-and-induce-anti-tumor-immunity
#9
Jewell N Walters, Bernadette Ferraro, Elizabeth K Duperret, Kimberly A Kraynyak, Jaemi Chu, Ashley Saint-Fleur, Jian Yan, Hy Levitsky, Amir S Khan, Niranjan Y Sardesai, David B Weiner
Tumor-associated antigens have emerged as important immunotherapeutic targets in the fight against cancer. Germline tumor antigens, such as WT1, Wilms' tumor gene 1, are overexpressed in many human malignancies but have low expression in somatic tissues. Recent vaccination approaches to target WT1 have been hampered by poor in vivo immune potency, likely due to the conserved self-antigen nature of WT1. In this study, we use a novel synthetic micro-consensus SynCon DNA vaccine approach with the goal of breaking tolerance and increasing vaccine immune potency...
February 22, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28237325/the-effect-of-lysophosphatidic-acid-together-with-interferon-tau-on-the-global-transcriptomic-profile-in-bovine-endometrial-cells
#10
Dorota Boruszewska, Ilona Kowalczyk-Zieba, Emilia Sinderewicz, Katarzyna Grycmacher, Joanna Staszkiewicz, Izabela Woclawek-Potocka
In cows, lysophosphatidic acid (LPA), which acts in an auto/paracrine manner, serves as a luteotropic factor during early pregnancy by stimulating progesterone and prostaglandin E2 secretion, thus protecting the bovine corpus luteum and early embryo development. Our hypothesis was that LPA exerted some local effects on the bovine endometrium prior to early embryo-maternal interactions and that interferon tau (IFNτ), the pregnancy recognition signal, modulated this action. In the present study, we applied an in vitro model involving whole-transcriptomic profiling to examine the effects of LPA on gene expression in bovine endometrial cells...
April 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28235976/immune-regulation-of-intrahepatic-regulatory-t-cells-in-fibrotic-livers-of-mice
#11
Xiaohui Zhang, Jinli Lou, Li Bai, Yu Chen, Sujun Zheng, Zhongping Duan
BACKGROUND Liver fibrosis is the result of chronic inflammation and repair, and many immune cells contribute to the process. Regulatory T cells (Tregs) mediate immune tolerance and are highly expressed in liver fibrosis. However, few reports have studied the specific effects of Tregs on regulating immune cells in liver fibrosis. The present study aimed to investigate the regulation of Tregs on intrahepatic immune cells in liver fibrosis by depleting Tregs in mice. MATERIAL AND METHODS Liver fibrosis was induced by carbon tetrachloride, and an anti-CD25 mAb (PC61) was used to deplete Tregs...
February 25, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28231415/encapsulating-an-immunosuppressant-enhances-tolerance-induction-by-siglec-engaging-tolerogenic-liposomes
#12
Lijuan Pang, Matthew S Macauley, Britni M Arlian, Corwin M Nycholat, James C Paulson
Unwanted antibody responses significantly impact human health, and current options for treating deleterious antibody responses largely rely on broad immunosuppressants that can compromise overall immunity. A desirable alternative is to induce antigen-specific immune tolerance. We have shown that co-presentation of antigen and ligands of B cell Siglecs (sialic acid-binding immunoglobulin-like lectin) on a liposomal nanoparticle induces antigen-specific tolerance. Although Siglec-engaging tolerance-inducing antigenic liposomes (STALs) induce robust B cell tolerance in naïve mice, the full potential of STALs requires long-term tolerance induction and suppression of an ongoing immune response...
February 23, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28229285/topics-on-vitamin-d-in-systemic-lupus-erythematosus-analysis-of-evidence-and-critical-literature-review
#13
António Marinho, Mariana Taveira, Carlos Vasconcelos
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multiorgan inflammation, linked to the loss of immune tolerance to self-antigens and the production of a diversity of autoantibodies. The phenotype and progression of SLE have been linked to a combination of environmental, genetic, and hormonal factors. One such environmental factor is vitamin D, a vital hormone with well-established effects on mineral metabolism, skeletal health, and effects on cardiovascular system. The purpose of this article is to make the analysis of evidence and literature review of the pleomorphic effects of Vitamin D in SLE...
February 22, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28229217/foxo3-estrogen-receptor-alpha-and-androgen-receptor-impact-tumor-growth-rate-and-infiltration-of-dendritic-cell-subsets-differentially-between-male-and-female-mice
#14
Matthew G Thompson, Daniel S Peiffer, Michelle Larson, Flor Navarro, Stephanie K Watkins
Tumors evade immune recognition and destruction in many ways including the creation of an immune-suppressive tumor microenvironment (TME). Dendritic cells (DC) that infiltrate the TME are tolerogenic, and suppress effector T cells and anti-tumor activity. Previous reports demonstrated that a key regulator of tolerance in DC is the transcription factor FOXO3. Gender disparity has been studied in cancer in relation to incidence, aggressiveness, and prognosis. Few studies have touched on the importance in relation to impact on the immune system...
February 22, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28228759/interleukin-35-producing-cd8%C3%AE-dendritic-cells-acquire-a-tolerogenic-state-and-regulate-t-cell-function
#15
Sergio Haller, Anaïs Duval, Romain Migliorini, Mathias Stevanin, Vanessa Mack, Hans Acha-Orbea
Dendritic cells (DCs) play a central role in shaping immunogenic as well as tolerogenic adaptive immune responses and thereby dictate the outcome of adaptive immunity. Here, we report the generation of a CD8α(+) DC line constitutively secreting the tolerogenic cytokine interleukin (IL)-35. IL-35 secretion led to impaired CD4(+) and CD8(+) T lymphocyte proliferation and interfered with their function in vitro and also in vivo. IL-35 was furthermore found to induce a tolerogenic phenotype on CD8α(+) DCs, characterized by the upregulation of CD11b, downregulation of MHC class II, a reduced costimulatory potential as well as production of the immunomodulatory molecule IL-10...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28228704/pd-1-and-pd-l1-immune-checkpoint-blockade-to-treat-breast-cancer
#16
REVIEW
Andreas D Hartkopf, Florin-Andrei Taran, Markus Wallwiener, Christina B Walter, Bernhard Krämer, Eva-Maria Grischke, Sara Y Brucker
Immune checkpoint inhibition represents a major recent breakthrough in the treatment of malignant diseases including breast cancer. Blocking the programmed death receptor-1 (PD-1) and its ligand, PD-L1, has shown impressive antitumor activity and may lead to durable long-term disease control, especially in the triple-negative subtypes of breast cancer (TNBC). Although immune checkpoint blockade is generally well tolerated, specific immune-related adverse events (irAEs) may occur. This review summarizes the clinical efficacy, perspectives, and future challenges of using PD-1/PD-L1-directed antibodies in the treatment of breast cancer...
December 2016: Breast Care
https://www.readbyqxmd.com/read/28228426/probiotics-lactobacillus-gasseri-ks-13-bifidobacterium-bifidum-g9-1-and-bifidobacterium-longum-mm-2-improve-rhinoconjunctivitis-specific-quality-of-life-in-individuals-with-seasonal-allergies-a-double-blind-placebo-controlled-randomized-trial
#17
Jennifer C Dennis-Wall, Tyler Culpepper, Carmelo Nieves, Cassie C Rowe, Alyssa M Burns, Carley T Rusch, Ashton Federico, Maria Ukhanova, Sheldon Waugh, Volker Mai, Mary C Christman, Bobbi Langkamp-Henken
Background: Rhinoconjunctivitis-specific quality of life is often reduced during seasonal allergies. The Mini Rhinoconjunctivitis Quality of Life Questionnaire (MRQLQ) is a validated tool used to measure quality of life in people experiencing allergies (0 = not troubled to 6 = extremely troubled). Probiotics may improve quality of life during allergy season by increasing the percentage of regulatory T cells (Tregs) and inducing tolerance.Objective: The objective of this study was to determine whether consuming Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and B...
February 22, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28228278/immunopathogenesis-of-rheumatoid-arthritis
#18
REVIEW
Gary S Firestein, Iain B McInnes
Rheumatoid arthritis (RA) is the most common inflammatory arthropathy. The majority of evidence, derived from genetics, tissue analyses, models, and clinical studies, points to an immune-mediated etiology associated with stromal tissue dysregulation that together propogate chronic inflammation and articular destruction. A pre-RA phase lasting months to years may be characterized by the presence of circulating autoantibodies, increasing concentration and range of inflammatory cytokines and chemokines, and altered metabolism...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28226225/thymic-epithelial-cells
#19
Jakub Abramson, Graham Anderson
IntrathymicTcell development is a complex process that depends upon continuous guidance from thymus stromal cell microenvironments. The thymic epithelium within the thymic stroma comprises highly specialized cells with a high degree of anatomic, phenotypic, and functional heterogeneity. These properties are collectively required to bias thymocyte development toward production of self-tolerant and functionally competent T cells. The importance of thymic epithelial cells (TECs) is evidenced by clear links between their dysfunction and multiple diseases where autoimmunity and immunodeficiency are major components...
February 10, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28225165/the-contrasting-role-of-th17-immunity-in-human-health-and-disease
#20
Edwin Hoe, Jeremy Anderson, Jordan Nathanielsz, Zheng Quan Toh, Rachel Marimla, Anne Balloch, Paul V Licciardi
The human immune system is a tightly regulated network that protects the host from disease. An important aspect of this is the balance between pro-inflammatory Th17 cells and anti-inflammatory Treg cells in maintaining immune homeostasis. Foxp3+ Treg are critical for sustaining immune tolerance through IL-10 and TGF-β while RORγt+ Th17 cells promote immunopathology and auto-inflammatory diseases through the actions of IL-17A, IL-21 and IL-22. Therefore, the imbalance between Treg and Th17 cells can result in serious pathology in many organs and tissues in the body...
February 22, 2017: Microbiology and Immunology
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