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Ayako Kurioka, Paul Klenerman, Chris Willberg
New data in the worlds of both innate-like CD8+ T cells and NK cells have, in parallel, clarified some of the phenotypes of these cells and also their associated functions. While these cells are typically viewed entirely separately, the emerging innate functions of T cells and, similarly, the adaptive functions of NK cells suggest that many behaviours can be considered in parallel. In this review we compare the innate functions of CD8+ T cells (especially Mucosal Associated Invariant T cells) and those of NK cells and how these relate to expression of phenotypic markers, especially CD161 and CD56...
March 14, 2018: Immunology
Trisha M Finlay, Alexandra L Palmer, Shalina S Ousman
Neutrophils are essential in the fight against invading pathogens. They utilize antimicrobial effector mechanisms such as phagocytosis, release of proteases and other antimicrobial products, robust oxidative bursts, and NETs to combat infections. Neutrophils also modulate immune responses through the production of eicosanoids, cytokines and chemokines as well as via direct communication with other immune cells. This system of high intensity offense against pathogens is exquisitely balanced through regulation to limit damage to host tissue...
March 13, 2018: Immunology
Jodie Stephenson, Erik Nutma, Paul van der Valk, Sandra Amor
Neurodegenerative diseases, the leading cause of morbidity and disability is gaining increased attention as it imposes a considerable socioeconomic impact, due in part to the ageing community. Neuronal damage is a pathological hallmark of Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, spinocerebellar ataxia and multiple sclerosis, although such damage is also observed following neurotropic viral infections, stroke, genetic white matter diseases and paraneoplastic disorders...
March 7, 2018: Immunology
Daniëlle Vaartjes, Kutty Selva Nandakumar, Rikard Holmdahl, Bruno Raposo
High salt consumption has since long been associated with elevated blood pressure and cardiovascular disease. Recently, mouse studies suggested that a high dietary salt intake exacerbates the clinical manifestations of autoimmunity. Using naïve cells ex vivo after pre-exposure of mice to high salt intake, we show that increased salt exposure affects the viability and effector functions of immune cells. CD4+ T cells evidenced a pro-inflammatory phenotype characterized by increased secretion of IFNγ and IL-17A, when exposed to high salt concentrations in vitro...
March 7, 2018: Immunology
Dai Yu-Mei, Hai-Ying Liu, Yun-Feng Liu, Yuan Zhang, Wei He
The engagement of Epstein-Barr virus (EBV)-induced protein ligands in γδ T cell-mediated anti-EBV immunity especially in EBV associated B cell malignancies has not been fully elucidated. Previously we reported the overexpression of human MutS homologue 2(hMSH2), a stress inducible protein ligand for human γδ T cells, on EBV-transformed B lymphoblastic cell lines (B-LCLs). In this study, we first generated EBV-transformed B-LCLs from peripheral blood mononuclear cells (PBMCs) of healthy volunteers with B95-8 cellular supernatant and cyclosporine A...
March 7, 2018: Immunology
Rebecca J Brownlie, Rose Zamoyska, Robert J Salmond
A number of polymorphisms in immune-regulatory genes have been identified as risk factors for the development of autoimmune disease. PTPN22, that encodes a tyrosine phosphatase, has been associated with the development of several autoimmune diseases including type 1 diabetes, rheumatoid arthritis and systemic lupus erythematosus. PTPN22 regulates the activity and effector functions of multiple important immune cell types including lymphocytes, granulocytes and myeloid cells. In this review, we describe the role of PTPN22 in regulating T cell activation and effector responses...
March 7, 2018: Immunology
Santosh Kumar
Natural killer (NK) cells express an array of germ-line encoded receptors that are capable of triggering cytotoxicity. NK cells tend to express many members of a given family of signaling molecules. The presence of many activating receptors and many members of a given family of signaling molecules can enable NK cells to detect different kinds of target cells, and to mount different kinds of responses. This contributes also to the robustness of NK cells responses; cytotoxic functions of NK cells often remain unaffected in the absence of selected signaling molecules...
March 7, 2018: Immunology
Aditya Rayasam, Martin Hsu, Julie A Kijak, Lee Kissel, Gianna Hernandez, Matyas Sandor, Zsuzsanna Fabry
Stroke is one of the leading causes of death and disability worldwide. The long-standing dogma that stroke is exclusively a vascular disease has been questioned by extensive clinical findings of immune factors that are associated mostly with inflammation after stroke. These have been confirmed in preclinical studies using experimental animal models. It is now accepted that inflammation and immune mediators are critical in acute and long-term neuronal tissue damage and healing following thrombotic and ischemic stroke...
March 1, 2018: Immunology
Bahadur Singh Gurjar, T Manikanta Sriharsha, Angika Bhasym, Savit Prabhu, Mamta Puraswani, Priyanka Khandelwal, Himanshi Saini, Savita Saini, Anita Kamra Verma, Priyadarshini Chatterjee, Prasenjit Gucchait, Vineeta Bal, Anna George, Satyajit Rath, Arvind Sahu, Amita Sharma, Pankaj Hari, Aditi Sinha, Arvind Bagga
We previously reported that Indian pediatric patients of atypical hemolytic-uremic syndrome (aHUS) showed high frequencies of anti-complement factor H (FH) autoantibodies that are correlated with homozygous deletion of the genes for FH-related proteins 1 and 3 (FHR1 and FHR3) (FHR1/3-/-). We now report that Indian pediatric aHUS patients without anti-FH autoantibodies also showed modestly higher frequencies of the FHR1/3-/- genotype. Further, when we characterized epitope specificities and binding avidities of anti-FH autoantibodies in aHUS patients, most anti-FH autoantibodies were directed towards the FH cell-surface anchoring polyanionic binding site-containing C-terminal short conservative regions (SCRs) 17-20 with higher binding avidities than for native FH...
February 27, 2018: Immunology
Sultan Damgaci, Arig Ibrahim-Hashim, Pedro M Enriquez-Navas, Shari Pilon-Thomas, Albert Guvenis, Robert J Gillies
Due to imbalances between vascularity and cellular growth patterns, the tumor microenvironment harbors multiple metabolic stressors including hypoxia and acidosis, which have significant influence on remodeling both tumor and peritumoral tissues. These stressors are also immunosuppressive and can contribute to escape from immune surveillance. Understanding these effects and characterizing the pathways involved can identify new targets for therapy and may redefine our understanding of traditional anti-tumor therapies...
February 27, 2018: Immunology
Ralf Willebrand, Markus Kleinewietfeld
The immune system evolved to protect organisms from invading pathogens. A network of pro- and anti-inflammatory cell types equipped with special effector molecules guarantees efficient elimination of intruders like viruses and bacteria. However, imbalances can lead to an exceeding response of effector cells incurring autoimmune or allergic diseases. An interplay of genetic and environmental factors contributes to autoimmune diseases and recent studies provided evidence for an impact of dietary habits on the immune status and related disorders...
February 21, 2018: Immunology
Lei Yu, Feng-Jie Wang, Yan-Fang Cui, Dong Li, Wen-Rong Yao, Gui-Bo Yang
Interleukin-22 (IL-22) is a potential therapeutic agent for diseases driven by epithelial injury. To characterize the IL-22 expressed by rhesus macaques, animals irreplaceable for human disease researches, rhesus macaque IL-22 (rhIL-22) was cloned and expressed, and its biological activity and in vivo distribution were examined. It was found that rhIL-22 gene consists of 5 introns and 6 exons, including a short non-coding exon starting 22bp downstream of a putative TATA box. The amino acid sequence of rhIL-22 showed 95...
February 21, 2018: Immunology
Ellyn Hughes, Martin Scurr, Emma Campbell, Emma Jones, Andrew Godkin, Awen Gallimore
The power of T cells for cancer treatment has been demonstrated by the success of co-inhibitory receptor blockade and adoptive T cell immunotherapies. These treatments are highly successful for certain cancers, but are often personalised, expensive and associated with harmful side effects. Other T cell modulating drugs may provide additional means of improving immune responses to tumours without these disadvantages. Conventional chemotherapeutic drugs are traditionally used to target cancers directly, however it is clear that some also have significant immune-modulating effects that can be harnessed to target tumours...
February 20, 2018: Immunology
Andrew Chancellor, Stephan D Gadola, Salah Mansour
The family of non-classical MHC class-I like CD1 molecules has an emerging role in human disease. Group 1 CD1 includes CD1a, CD1b, and CD1c which function to display lipids on the cell surface of antigen presenting cells for direct recognition by T cells. The recent advent of CD1 tetramers and the identification of novel lipid ligands has contributed towards the increasing number of CD1 restricted T cell clones captured. These advances have helped to identify novel donor unrestricted and semi-invariant T cell populations in humans and new mechanisms of T cell recognition...
February 20, 2018: Immunology
Samanta C Funes, Mariana Rios, Jorge Escobar-Vera, Alexis M Kalergis
Macrophages are extremely heterogeneous and plastic cells with an important role not only in physiological conditions, but also during inflammation (both for initiation and resolution). In the early 90s, two different phenotypes of macrophages were described: one of them called classically activated (or inflammatory) macrophages (M1) and the other alternatively activated (or wound-healing) macrophages (M2). Currently, it is known that functional polarization of macrophages only into two groups is an over simplified description of macrophage heterogeneity and plasticity, indeed, it is necessary to consider a continuum of functional states...
February 18, 2018: Immunology
Gao An, Xin Zhang, Wenjun Wang, Qiong Huang, Yan Li, Shan Shan, Chris J Corrigan, Wei Wang, Sun Ying
It has been suggested that interleukin 33 (IL-33) plays an important role in the pathogenesis of asthma through a variety of pathways, but its role in airways fibrosis in asthma has not been fully elucidated. In the present study we evaluated changes in the expression of extracellular matrix proteins (ECMs) as well as matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in an IL-33-induced, antigen-independent murine surrogate of asthma as well as a conventional surrogate employing per-nasal challenge of mice previously sensitised to produce an IgE response to ovalbumin (OVA)...
February 18, 2018: Immunology
Ciara Ordoñez, Hannah P Savage, Musharaf Tarajia, René Rivera, Cheyenne Weeks-Galindo, Dilcia Sambrano, Lee Riley, Patricia L Fernandez, Nicole Baumgarth, Amador Goodridge
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. The cellular immune response to Mycobacteria has been characterized extensively, but the antibody response remains underexplored. The present study aimed to examine whether host or bacterial phospholipids induce secretion of IgM, and specifically anti-phospholipid IgM, antibodies by B cells and to identify the responsible B cell subset. Here we show that peritoneal B cells responded to lipid antigens by secreting IgM antibodies. Specifically, stimulation with Mycobacterium tuberculosis H37Rv total lipids resulted in significant induction of total and anti-phosphatidylcholine IgM...
February 18, 2018: Immunology
Haiyan Xu, Li Cai, Lili Zhang, Guojue Wang, Rongli Xie, Yongshuai Jiang, Yuanyang Yuan, Hong Nie
Paeoniflorin (PF), extracted from the root of Paeonia lactiflora Pall, exhibits anti-inflammation properties in several autoimmune diseases. Osteoclast, the only somatic cell with bone resorbing capacity, was the direct cause of bone destruction in rheumatoid arthritis (RA) and its mouse model, such as collagen induced arthritis(CIA). The objective of this study is to estimate the effect of PF on CIA mice, and explore the mechanism of PF on bone destruction. We demonstrated that PF treatment significantly ameliorated CIA via inflammatory response inhibition and bone destruction suppression...
February 17, 2018: Immunology
Xuanxuan Guo, Xiang Fang, Guodan He, M Haidar Zaman, Xibin Fei, Wei Qiao, Guo-Min Deng
Skin injury is the second most common clinical manifestation in patients with SLE. Neutrophils are crucial effector cells in immune system. The significance of neutrophils in the pathogenesis of SLE is not clear. This study is to explore the role of neutrophils in skin damage of SLE. We used lupus-prone mice and C57BL/6 mice model of lupus serum IgG induced skin inflammation to investigate neutrophils role in skin damage of SLE. We found a few neutrophils infiltrated in the inflammatory sites of skin in lupus-prone mice and lupus IgG induced skin damaged mice model...
February 16, 2018: Immunology
J K Skelton, A M Ortega-Prieto, M Dorner
Humanized mice are increasingly appreciated as an incredibly powerful platform for infectious disease research. The often very narrow species tropism of many viral infections, coupled with the sometimes-misleading results from preclinical studies in animal models (e.g. fatal immune reactions in the PEARL study 1 ) further emphasize the need for more predictive model systems based on human cells rather than surrogates. Humanized mice represent such a model and have been greatly enhanced in regards to their immune system reconstitution as well as immune functionality in the past years, resulting in their recommendation as pre-clinical model by the US Food and Drug Administration...
February 15, 2018: Immunology
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