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Adaptive immunity

Carlos Alfredo Silva-Islas, Perla D Maldonado
Nuclear Factor Erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates the expression of genes involved in the metabolism, immune response, cellular proliferation, and other processes; however, the attention has been focused on the study of its ability to induce the expression of proteins involved in the antioxidant defense. Nrf2 is mainly regulated by Kelch-like ECH-associated protein 1 (Keap1), an adapter substrate of Cullin 3 (Cul3) ubiquitin E3 ligase complex. Keap1 represses Nrf2 activity in the cytoplasm by its sequestering, ubiquitination and proteosomal degradation...
June 15, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Mohamed B Ezzelarab
Regulatory T cells (Treg) are currently being evaluated in clinical allotransplantation for tolerance induction, with proven safety in humans with autoimmune diseases and graft-versus-host disease. A considerable amount of recent data suggests that additional factors may need to be validated, including the stability and commitment of newly discovered Treg subsets under inflammatory conditions, to further warrant safe and effective Treg-based therapeutic approaches. This review explores the opportunities and challenges of Treg-based cell therapy in xenotransplantation...
May 2018: Xenotransplantation
Guerard W Byrne
The major histocompatibility complex class I and class II human leukocyte antigens (HLA) play a central role in adaptive immunity but are also the dominant polymorphic proteins targeted in allograft rejection. Sensitized patients with high levels of panel-reactive anti-HLA antibody (PRA) are at risk of early allograft injury, rejection, reduced allograft survival and often experience prolonged waiting times prior to transplantation. Xenotransplantation, using genetically modified porcine organs, offers a unique source of donor organs for these highly sensitized patients if the anti-HLA antibody, which places the allograft at risk, does not also enhance anti-pig antibody reactivity responsible for xenograft rejection...
May 2018: Xenotransplantation
Louis S Ates, Fadel Sayes, Wafa Frigui, Roy Ummels, Merel P M Damen, Daria Bottai, Marcel A Behr, Jeroen W J van Heijst, Wilbert Bitter, Laleh Majlessi, Roland Brosch
Tuberculosis is the deadliest infectious disease worldwide. Although the BCG vaccine is widely used, it does not efficiently protect against pulmonary tuberculosis and an improved tuberculosis vaccine is therefore urgently needed. Mycobacterium tuberculosis uses different ESX/Type VII secretion (T7S) systems to transport proteins important for virulence and host immune responses. We recently reported that secretion of T7S substrates belonging to the mycobacteria-specific Pro-Glu (PE) and Pro-Pro-Glu (PPE) proteins of the PGRS (polymorphic GC-rich sequences) and MPTR (major polymorphic tandem repeat) subfamilies required both a functional ESX-5 system and a functional PPE38/71 protein for secretion...
June 18, 2018: PLoS Pathogens
Roland Wunderlich, Paul Friedrich Rühle, Lisa Deloch, Franz Roedel, Rainer Fietkau, Udo S Gaipl, Benjamin Frey
PURPOSE: Previous investigations revealed influences of irradiation up to 2.0 Gy on the cytokine secretion profile of inflammatory, peritoneal mouse macrophages (pMФ). This raised the question if those alterations impact on dendritic cells and consecutive T-cell responses. Further, the impact of irradiation directly on pMФ capacity to induce T-cell responses was analyzed. MATERIALS AND METHODS: pMФ were LPS-activated, irradiated and the expression of activation markers was assessed...
June 18, 2018: International Journal of Radiation Biology
Qiong Zhang, Robert Berkey, Joshua J Blakeslee, Jinshan Lin, Xianfeng Ma, Harley King, Anna Liddle, Liang Guo, Teun Munnik, Xuemin Wang, Shunyuan Xiao
Plants use a tightly regulated immune system to fight off various pathogens. Phospholipase D (PLD) and its product, phosphatidic acid, have been shown to influence plant immunity; however, the underlying mechanisms remain unclear. Here, we show that the Arabidopsis mutants pldα1 and pldδ respectively exhibited enhanced resistance and enhanced susceptibility to both well- and poorly-adapted powdery mildew pathogens, and a virulent oomycete pathogen, indicating that PLDα1 negatively while PLDδ positively modulate post-penetration resistance...
April 18, 2018: Journal of Experimental Botany
Daniela Carnevale, Philip Wenzel
No abstract text is available yet for this article.
June 15, 2018: Cardiovascular Research
Emily R Burnside, Fred De Winter, Athanasios Didangelos, Nicholas D James, Elena-Cristina Andreica, Hugo Layard-Horsfall, Elizabeth M Muir, Joost Verhaagen, Elizabeth J Bradbury
Chondroitinase ABC is a promising preclinical therapy that promotes functional neuroplasticity after CNS injury by degrading extracellular matrix inhibitors. Efficient delivery of chondroitinase ABC to the injured mammalian spinal cord can be achieved by viral vector transgene delivery. This approach dramatically modulates injury pathology and restores sensorimotor functions. However, clinical development of this therapy is limited by a lack of ability to exert control over chondroitinase gene expression. Prior experimental gene regulation platforms are likely to be incompatible with the non-resolving adaptive immune response known to occur following spinal cord injury...
June 14, 2018: Brain: a Journal of Neurology
Frédéric Rieux-Laucat, Aude Magérus-Chatinet, Bénédicte Neven
The autoimmune lymphoproliferative syndrome (ALPS) is a non-malignant and non-infectious uncontrolled proliferation of lymphocytes accompanied by autoimmune cytopenia. The genetic etiology of the ALPS was described in 1995 by the discovery of the FAS gene mutations. The related apoptosis defect accounts for the accumulation of autoreactive lymphocytes as well as for specific clinical and biological features that distinguish the ALPS-FAS from other monogenic defects of this apoptosis pathway, such as FADD and CASPASE 8 deficiencies...
June 17, 2018: Journal of Clinical Immunology
Aparna P Sajja, Aditya A Joshi, Heather L Teague, Amit K Dey, Nehal N Mehta
Preclinical and clinical research provide strong evidence that chronic, systemic inflammation plays a key role in development and progression of atherosclerosis. Indeed, chronic inflammatory diseases, such as psoriasis, are associated with accelerated atherosclerosis and increased risk of cardiovascular events. Contemporary research has demonstrated plausible mechanistic links between immune cell dysfunction and cardiometabolic disease in psoriasis. In this review, we describe the role of potential common immunological mechanisms underlying both psoriasis and atherogenesis...
2018: Frontiers in Immunology
Sara Scutera, Valentina Salvi, Luisa Lorenzi, Giorgia Piersigilli, Silvia Lonardi, Daniela Alotto, Stefania Casarin, Carlotta Castagnoli, Erica Dander, Giovanna D'Amico, Silvano Sozzani, Tiziana Musso
Mesenchymal stromal cells (MSCs) exert immunosuppressive effects on immune cells including dendritic cells (DCs). However, many details of the bidirectional interaction of MSCs with DCs are still unsolved and information on key molecules by which DCs can modulate MSC functions is limited. Here, we report that osteopontin (OPN), a cytokine involved in homeostatic and pathophysiologic responses, is constitutively expressed by DCs and regulated in the DC/MSC cocultures depending on the activation state of MSCs...
2018: Frontiers in Immunology
Robert W Wilkinson, Andrew J Leishman
Significant advances have been made to identify effective therapies that either restore or generate de novo a patient's immune response to cancer, so-called immunotherapy or immuno-oncology (IO) therapies. Some tumors overcome immune surveillance by promoting mechanisms to evade or suppress the immune system. This conference report highlights the clinical promise and current challenges of IO therapy, including the use of immune-checkpoint antagonist monoclonal antibodies. Furthermore, this report investigates advances in preclinical modeling of cancer immunobiology and how this is helping our understanding of which patients will receive clinical benefits from current immune-checkpoint treatment...
2018: Frontiers in Immunology
Ahmed El-Shamy, Andrea D Branch, Thomas D Schiano, Peter D Gorevic
The complement system bridges innate and adaptive immunity against microbial infections, with viral infection being a major trigger. Activation of the classical, alternative, and lectin pathways have been reported in chronic hepatitis C virus (HCV) infection and/or cryoglobulinemia. HCV infection leads to dysregulation of complement-mediated immune responses. Clinical and experimental evidence support involvement of complement in intra- and extrahepatic manifestations of HCV infection, such as liver fibrosis and type II cryoglobulinemia...
2018: Frontiers in Immunology
Vera Francisco, Jesús Pino, Victor Campos-Cabaleiro, Clara Ruiz-Fernández, Antonio Mera, Miguel A Gonzalez-Gay, Rodolfo Gómez, Oreste Gualillo
Obesity is an epidemic disease characterized by chronic low-grade inflammation associated with a dysfunctional fat mass. Adipose tissue is now considered an extremely active endocrine organ that secretes cytokine-like hormones, called adipokines, either pro- or anti-inflammatory factors bridging metabolism to the immune system. Leptin is historically one of most relevant adipokines, with important physiological roles in the central control of energy metabolism and in the regulation of metabolism-immune system interplay, being a cornerstone of the emerging field of immunometabolism...
2018: Frontiers in Physiology
Y Du, R Weide, Z Zhao, P Msimuko, F Govers, K Bouwmeester
Late blight disease caused by the plant pathogenic oomycete pathogen Phytophthora infestans is one of the most limiting factors in potato production. P. infestans is able to overcome introgressed late blight resistance by adaptation of effector genes. AVR1 is an RXLR effector that triggers immune responses when recognized by the potato resistance protein R1. P. infestans isolates avirulent on R1 plants were found to have AVR1 variants that are recognized by R1. Virulent isolates though, lack AVR1 but do contain a close homologue of AVR1, named A-L, of which all variants escape recognition by R1...
March 2018: Studies in Mycology
Paul K Ziegler, Julia Bollrath, Charles K Pallangyo, Takaji Matsutani, Özge Canli, Tiago De Oliveira, Michaela A Diamanti, Nina Müller, Jaba Gamrekelashvili, Tracy Putoczki, David Horst, Arun K Mankan, Meryem G Öner, Susanna Müller, Josef Müller-Höcker, Thomas Kirchner, Julia Slotta-Huspenina, M Mark Taketo, Thomas Reinheckel, Stefan Dröse, Andrew C Larner, Winfried S Wels, Matthias Ernst, Tim F Greten, Melek C Arkan, Thomas Korn, Dagmar Wirth, Florian R Greten
In colorectal cancer patients, a high density of cytotoxic CD8+ T cells in tumors is associated with better prognosis. Using a Stat3 loss-of-function approach in two wnt/β-catenin-dependent autochthonous models of sporadic intestinal tumorigenesis, we unravel a complex intracellular process in intestinal epithelial cells (IECs) that controls the induction of a CD8+ T cell based adaptive immune response. Elevated mitophagy in IECs causes iron(II)-accumulation in epithelial lysosomes, in turn, triggering lysosomal membrane permeabilization...
June 11, 2018: Cell
Norah L Smith, Ravi K Patel, Arnold Reynaldi, Jennifer K Grenier, Jocelyn Wang, Neva B Watson, Kito Nzingha, Kristel J Yee Mon, Seth A Peng, Andrew Grimson, Miles P Davenport, Brian D Rudd
Heterogeneity is a hallmark feature of the adaptive immune system in vertebrates. Following infection, naive T cells differentiate into various subsets of effector and memory T cells, which help to eliminate pathogens and maintain long-term immunity. The current model suggests there is a single lineage of naive T cells that give rise to different populations of effector and memory T cells depending on the type and amounts of stimulation they encounter during infection. Here, we have discovered that multiple sub-populations of cells exist in the naive CD8+ T cell pool that are distinguished by their developmental origin, unique transcriptional profiles, distinct chromatin landscapes, and different kinetics and phenotypes after microbial challenge...
June 6, 2018: Cell
Edward C Hutchinson
This infographic briefly summarises the natural history, replication cycle, and pathogenesis of influenza viruses, the cause of seasonal influenza and of influenza pandemics. Influenza viruses infect many vertebrates, with Influenza A, B and C viruses (IAV, IBV, and ICV) infecting humans. High mutation rates allow the evasion of immunity. IAV from different host species can 'reassort' their segmented genomes, producing pandemic strains that are antigenically novel but otherwise well adapted to humans. The 'Great Influenza' pandemic of 1918 remains the worst outbreak of infectious disease in history...
June 13, 2018: Trends in Microbiology
Majid Asadi-Ghalehni, Mohamad Javad Rasaee, Nabiollah Namvar Asl, Masood Khosravani, Masoumeh Rajabibazl, Saeed Khalili, Helmout Modjtahedi, Esmaeil Sadroddiny
Over expression of the epidermal growth factor receptor (EGFR) in many human epithelial tumors has been correlated with disease progression and poor prognosis. EGFR-inhibiting immunotherapy has already been introduced in cancer therapy. Peptide displaying phage particles in eukaryotic hosts can behave as antigen carriers, able to activate the innate immune system and to elicit adaptive immunity. Herein, the M13-pAK8-VIII phagemid plasmid was engineered to contain the sequences for an EGFR mimotope along with the L2 extracellular domain of EGFR (EM-L2) which would produce the final peptide-phage vaccine...
June 2018: Iranian Journal of Allergy, Asthma, and Immunology
Ulrike G Glaser, Joachim Fandrey
Hypoxia due to rapid tumor growth with impaired neovascularization and inflammation resulting from immune cell activation are hallmarks of cancer. Hypoxia-inducible factors (HIFs) control transcriptional adaptation in response to low oxygen conditions, both in tumor and immune cells. In addition, sphingolipids become increasingly recognized as important cell mediators in tumor and inflammatory hypoxia. Recent studies have identified acid sphingomyelinase (ASM), a central enzyme in the sphingolipid metabolism, as a regulator of several types of stress stimuli pathways and an important player in the tumor microenvironment...
June 1, 2018: Biological Chemistry
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