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Clinical & Translational Immunology

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https://www.readbyqxmd.com/read/29670745/induction-of-immunity-following-vaccination-with-a-chemically-attenuated-malaria-vaccine-correlates-with-persistent-antigenic-stimulation
#1
Jennifer M Reiman, Sanjai Kumar, Ingrid B Rodriguez, Sedami Gnidehou, Koichi Ito, Danielle I Stanisic, Moses Lee, Virginia McPhun, Victoria Majam, Nicole M Willemsen, Michael R Batzloff, Amber I Raja, Brad Dooley, Stephen L Hoffman, Stephanie K Yanow, Michael F Good
Objectives: Blood stage malaria parasites attenuated with seco-cyclopropyl pyrrolo indole (CPI) analogues induce robust immunity in mice to homologous and heterologous malaria parasites and are being considered for the development of a human vaccine. However, it is not understood how attenuated parasites induce immunity. We showed that following vaccination, parasite DNA persisted in blood for several months, raising the possibility that ongoing immune stimulation may be critical. However, parasites were not seen microscopically beyond 24 h postvaccination...
2018: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29632667/immune-regulation-of-the-unfolded-protein-response-at-the-mucosal-barrier-in-viral-infection
#2
REVIEW
Ran Wang, Md Moniruzzaman, Eric Shuffle, Rohan Lourie, Sumaira Z Hasnain
Protein folding in the endoplasmic reticulum (ER) is subject to stringent quality control. When protein secretion demand exceeds the protein folding capacity of the ER, the unfolded protein response (UPR) is triggered as a consequence of ER stress. Due to the secretory function of epithelial cells, UPR plays an important role in maintaining epithelial barrier function at mucosal sites. ER stress and activation of the UPR are natural mechanisms by which mucosal epithelial cells combat viral infections. In this review, we discuss the important role of UPR in regulating mucosal epithelium homeostasis...
2018: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29610662/a-feasibility-study-association-between-gut-microbiota-enterotype-and-antibody-response-to-seasonal-trivalent-influenza-vaccine-in-adults
#3
Nick Shortt, Hazel Poyntz, Wayne Young, Angela Jones, Aurélie Gestin, Anna Mooney, Darmiga Thayabaran, Jenny Sparks, Tess Ostapowicz, Audrey Tay, Sally Poppitt, Sarah Elliott, Georgia Wakefield, Amber Parry-Strong, Jacqui Ralston, Olivier Gasser, Richard Beasley, Mark Weatherall, Irene Braithwaite, Elizabeth Forbes-Blom
Objective: We investigated the potential feasibility of a randomized controlled trial of a nutritional intervention that may alter human gut microbiota and support immune defence against respiratory tract infection in adults (Proposed Study). Methods: In total, 125 healthy adults aged 18-64 participated in a 6-month study that measured antibody response to the seasonal trivalent influenza vaccine. We assessed completion rates, procedure adherence rates and the influence of possible exclusion criteria on potential recruitment into the Proposed Study...
2018: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29610661/regulatory-t-cell-heterogeneity
#4
EDITORIAL
Kirsten A Ward-Hartstonge, Ajithkumar Vasanthakumar
No abstract text is available yet for this article.
2018: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29497530/unravelling-the-molecular-basis-for-regulatory-t-cell-plasticity-and-loss-of-function-in-disease
#5
REVIEW
Timothy Sadlon, Cheryl Y Brown, Veronika Bandara, Christopher M Hope, John E Schjenken, Stephen M Pederson, James Breen, Alistair Forrest, Marc Beyer, Sarah Robertson, Simon C Barry
Regulatory T cells (Treg) are critical for preventing autoimmunity and curtailing responses of conventional effector T cells (Tconv). The reprogramming of T-cell fate and function to generate Treg requires switching on and off of key gene regulatory networks, which may be initiated by a subtle shift in expression levels of specific genes. This can be achieved by intermediary regulatory processes that include microRNA and long noncoding RNA-based regulation of gene expression. There are well-documented microRNA profiles in Treg and Tconv, and these can operate to either reinforce or reduce expression of a specific set of target genes, including FOXP3 itself...
2018: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29484187/vaccinating-for-natural-killer-cell-effector-functions
#6
REVIEW
Helen R Wagstaffe, Jason P Mooney, Eleanor M Riley, Martin R Goodier
Vaccination has proved to be highly effective in reducing global mortality and eliminating infectious diseases. Building on this success will depend on the development of new and improved vaccines, new methods to determine efficacy and optimum dosing and new or refined adjuvant systems. NK cells are innate lymphoid cells that respond rapidly during primary infection but also have adaptive characteristics enabling them to integrate innate and acquired immune responses. NK cells are activated after vaccination against pathogens including influenza, yellow fever and tuberculosis, and their subsequent maturation, proliferation and effector function is dependent on myeloid accessory cell-derived cytokines such as IL-12, IL-18 and type I interferons...
2018: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29484186/characterisation-of-anti-alpha-toxin-antibody-levels-and-colonisation-status-after-administration-of-an-investigational-human-monoclonal-antibody-medi4893-against-staphylococcus-aureus-alpha-toxin
#7
Alexey Ruzin, Yuling Wu, Li Yu, Xiang-Qing Yu, David E Tabor, Hoyin Mok, Christine Tkaczyk, Kathryn Jensen, Terramika Bellamy, Lorin Roskos, Mark T Esser, Hasan S Jafri
Objectives: MEDI4893 is a novel, long-acting human monoclonal antibody targeting Staphylococcus aureus (SA) alpha toxin (AT). This report presents the results of the exploratory analyses from a randomised phase 1 dose-escalation study in healthy human subjects receiving single intravenous MEDI4893 doses or placebo. Methods: Anti-AT antibodies and AT expression were measured as described previously. Nasal swabs were analysed by culture and PCR. Data were summarised by treatment groups and visits by using SAS System Version 9...
2018: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29484185/accumulation-of-il-17-v%C3%AE-6-%C3%AE-%C3%AE-t-cells-in-pregnant-mice-is-not-associated-with-spontaneous-abortion
#8
Barbara Polese, Virginie Gridelet, Sophie Perrier d'Hauterive, Chantal Renard, Carine Munaut, Henri Martens, David Vermijlen, Irah L King, Nathalie Jacobs, Vincent Geenen
Introduction: Pregnancy is an immune paradox. While the immune system is required for embryo implantation, placental development and progression of gestation, excessive inflammation is associated with pregnancy failure. Similarly, the cytokine IL-17A plays an important role in defence against extracellular pathogens, but its dysregulation can lead to pathogenic inflammation and tissue damage. Although expression of IL-17 has been reported during pregnancy, the cellular source of this cytokine and its relevance to gestation are not clear...
2018: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29484184/endoplasmic-reticulum-stress-in-the-development-of-multiple-myeloma-and-drug-resistance
#9
REVIEW
Nicholas Nikesitch, James M Lee, Silvia Ling, Tara Laurine Roberts
Multiple myeloma (MM) is a haematological malignancy of mature antibody-secreting plasma cells. Currently, MM is incurable, but advances in drug treatments have increased patient lifespan. One of the characteristics of MM is the excessive production of monoclonal immunoglobulin (also referred to as paraprotein). This high level of protein production induces endoplasmic reticulum (ER) stress, and proteasomal degradation of the paraprotein is required to avoid ER stress-induced cell death. Consequently, proteasomal inhibitors such as bortezomib have been particularly effective therapies...
2018: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29484183/human-foxp3-t-regulatory-cell-heterogeneity
#10
REVIEW
Audrey Mohr, Rajneesh Malhotra, Gaell Mayer, Guy Gorochov, Makoto Miyara
FOXP3-expressing CD4+ T regulatory (Treg) cells are instrumental for the maintenance of self-tolerance. They are also involved in the prevention of allergy, allograft rejection, foetal rejection during pregnancy and of exaggerated immune response towards commensal pathogens in mucosal tissues. They can also prevent immune responses against tumors and promote tumor progression. FOXP3-expressing Treg cells are not a homogenous population. The different subsets of Treg cells can have different functions or roles in the maintenance of immune homeostasis and can therefore be differentially targeted in the management of autoimmune diseases or in cancer...
2018: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29484182/regulatory-t-cells-in-renal-disease
#11
REVIEW
Maliha A Alikhan, Megan Huynh, A Richard Kitching, Joshua D Ooi
The kidney is vulnerable to injury, both acute and chronic from a variety of immune and metabolic insults, all of which at least to some degree involve inflammation. Regulatory T cells modulate systemic autoimmune and allogenic responses in glomerulonephritis and transplantation. Intrarenal regulatory T cells (Tregs), including those recruited to the kidney, have suppressive effects on both adaptive and innate immune cells, and probably also intrinsic kidney cells. Evidence from autoimmune glomerulonephritis implicates antigen-specific Tregs in HLA-mediated dominant protection, while in several human renal diseases Tregs are abnormal in number or phenotype...
2018: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29484181/rapid-loss-of-group-1-innate-lymphoid-cells-during-blood-stage-plasmodium-infection
#12
Susanna S Ng, Fernando Souza-Fonseca-Guimaraes, Fabian de Labastida Rivera, Fiona H Amante, Rajiv Kumar, Yulong Gao, Meru Sheel, Lynette Beattie, Marcela Montes de Oca, Camille Guillerey, Chelsea L Edwards, Rebecca J Faleiro, Teija Frame, Patrick T Bunn, Eric Vivier, Dale I Godfrey, Daniel G Pellicci, J Alejandro Lopez, Katherine T Andrews, Nicholas D Huntington, Mark J Smyth, James McCarthy, Christian R Engwerda
Objectives: Innate lymphoid cells (ILCs) share many characteristics with CD4+ T cells, and group 1 ILCs share a requirement for T-bet and the ability to produce IFNγ with T helper 1 (Th1) cells. Given this similarity, and the importance of Th1 cells for protection against intracellular protozoan parasites, we aimed to characterise the role of group 1 ILCs during Plasmodium infection. Methods: We quantified group 1 ILCs in peripheral blood collected from subjects infected with with Plasmodium falciparum 3D7 as part of a controlled human malaria infection study, and in the liver and spleens of Pc AS-infected mice...
2018: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29484180/a-vaccine-to-prevent-cervical-cancer-academic-and-industrial-collaboration-and-a-lasker-award
#13
EDITORIAL
Edward M Scolnick
No abstract text is available yet for this article.
2018: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29484179/genome-wide-association-studies-in-crohn-s-disease-past-present-and-future
#14
REVIEW
Bram Verstockt, Kenneth Gc Smith, James C Lee
Over the course of the past decade, genome-wide association studies (GWAS) have revolutionised our understanding of complex disease genetics. One of the diseases that has benefitted most from this technology has been Crohn's disease (CD), with the identification of autophagy, the IL-17/IL-23 axis and innate lymphoid cells as key players in CD pathogenesis. Our increasing understanding of the genetic architecture of CD has also highlighted how a failure to suppress aberrant immune responses may contribute to disease development - a realisation that is now being incorporated into the design of new treatments...
2018: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29333270/lessons-from-ten-years-of-genome-wide-association-studies-of-asthma
#15
REVIEW
Cristina T Vicente, Joana A Revez, Manuel A R Ferreira
Twenty-five genome-wide association studies (GWAS) of asthma were published between 2007 and 2016, the largest with a sample size of 157242 individuals. Across these studies, 39 genetic variants in low linkage disequilibrium (LD) with each other were reported to associate with disease risk at a significance threshold of P <5 × 10-8 , including 31 in populations of European ancestry. Results from analyses of the UK Biobank data ( n =380 503) indicate that at least 28 of the 31 associations reported in Europeans represent true-positive findings, collectively explaining 2...
December 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29333269/the-immune-system-of-the-liver-50-years-of-strangeness
#16
EDITORIAL
Michaela Lucas, Axel Kallies, Paul Klenerman
No abstract text is available yet for this article.
December 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29333268/progress-of-genome-wide-association-studies-of-ankylosing-spondylitis
#17
REVIEW
Zhixiu Li, Matthew A Brown
Ankylosing spondylitis (AS) is an immune-mediated arthritis which primarily affects the spine and sacroiliac joints. Significant progress has been made in discovery of genetic associations with AS by genome-wide association studies (GWAS) over past decade. These findings have uncovered novel pathways involved pathogenesis of the disease and have led to introduction of novel therapeutic treatments for AS. In this Review, we discuss the genetic variations associated with AS identified by GWAS, the major pathways revealed by these AS-associated variations and critical cell types involved in AS development...
December 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29333267/type-1-diabetes-genome-wide-association-studies-not-to-be-lost-in-translation
#18
REVIEW
Flemming Pociot
Genetic studies have identified >60 loci associated with the risk of developing type 1 diabetes (T1D). The vast majority of these are identified by genome-wide association studies (GWAS) using large case-control cohorts of European ancestry. More than 80% of the heritability of T1D can be explained by GWAS data in this population group. However, with few exceptions, their individual contribution to T1D risk is low and understanding their function in disease biology remains a huge challenge. GWAS on its own does not inform us in detail on disease mechanisms, but the combination of GWAS data with other omics-data is beginning to advance our understanding of T1D etiology and pathogenesis...
December 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29326816/immune-checkpoint-inhibition-prospects-for-prevention-and-therapy-of-hepatocellular-carcinoma
#19
REVIEW
Caryn L Elsegood, Janina Ee Tirnitz-Parker, John K Olynyk, George Ct Yeoh
The global prevalence of liver cancer is rapidly rising, mostly as a result of the amplified incidence rates of viral hepatitis, alcohol abuse and obesity in recent decades. Treatment options for liver cancer are remarkably limited with sorafenib being the gold standard for advanced, unresectable hepatocellular carcinoma but offering extremely limited improvement of survival time. The immune system is now recognised as a key regulator of cancer development through its ability to protect against infection and chronic inflammation, which promote cancer development, and eliminate tumour cells when present...
November 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29201362/a-generalized-quantitative-antibody-homeostasis-model-maintenance-of-global-antibody-equilibrium-by-effector-functions
#20
József Prechl
The homeostasis of antibodies can be characterized as a balanced production, target-binding and receptor-mediated elimination regulated by an interaction network, which controls B-cell development and selection. Recently, we proposed a quantitative model to describe how the concentration and affinity of interacting partners generates a network. Here we argue that this physical, quantitative approach can be extended for the interpretation of effector functions of antibodies. We define global antibody equilibrium as the zone of molar equivalence of free antibody, free antigen and immune complex concentrations and of dissociation constant of apparent affinity: [Ab]=[Ag]=[AbAg]= K D ...
November 2017: Clinical & Translational Immunology
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