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Immunology

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https://www.readbyqxmd.com/read/27861817/a-novel-spontaneous-mutation-in-the-tap2-gene-unravels-its-role-in-macrophage-survival
#1
Antonio Lapenna, Ibrahim Omar, Michael Berger
Here we report a new mouse strain with a single point mutation in the type 2 transporter associated with antigen processing (TAP2). This strain randomly arose in one of our C57BL/6J mouse colony and was initially discovered due to lack of CD8(+) T cells in the periphery. Following our observation, we subsequently revealed a lack of cell surface major histocompatibility complex (MHC-I) expression, derived from TAP2 protein deficiency. Our strain, named eightless, has a C to T substitution in exon 5 resulting in a glutamine to stop codon substitution at position 285 in the TAP2 protein...
November 18, 2016: Immunology
https://www.readbyqxmd.com/read/27859243/effect-of-infusion-of-mabs-to-tnfrsf25-on-graft-rejection-in-allo-immune-mice-receiving-autologous-marrow-transplantation
#2
Reginald M Gorczynski, Hassan Sadozai, Fang Zhu, Ismat Khatri
Significant barriers to transplantation exist for individuals who are pre-sensitized to donor Ag and have high titres of donor-reactive Ab. We report the effect of autologous BMTx after myeloablation in pre-sensitized mice along with the use of mAbs to TNFRSF25, expressed on Tregs. C57BL/6 mice, which had been sensitized earlier with BALB/c skin allografts, received secondary BALB/c grafts after the primary grafts had been rejected. Subsequently, recipient mice underwent myeloablation with cyclophosphamide and busulphan and were injected with T-cell depleted bone marrow from CD45...
November 17, 2016: Immunology
https://www.readbyqxmd.com/read/27861821/effects-of-c2ta-genetic-polymorphisms-on-mhc-class-ii-expression-and-autoimmune-diseases
#3
Anthony Cy Yau, Fredrik Piehl, Tomas Olsson, Rikard Holmdahl
Antigen presentation by the major histocompatibility complex class II (MHC-II) to CD4(+) T cells is important in adaptive immune responses. The class II transactivator (CIITA in human and C2TA in mouse) is the master regulator of MHC-II gene expression. It coordinates the transcription factors necessary for the transcription of MHC-II molecules. In humans, genetic variation in C2ta has been associated with differential expression of MHC-II and susceptibility to autoimmune diseases. Here we made use of a C2ta congenic mouse strain (expressing MHC-II haplotype H-2(q) ) to investigate the effect of the natural genetic polymorphisms in type I promoter of C2ta on MHC-II expression and function...
November 15, 2016: Immunology
https://www.readbyqxmd.com/read/27859049/lps-primed-heterotolerant-dendritic-cells-suppress-experimental-autoimmune-uveoretintitis-by-multiple-mechanisms
#4
Izabela P Klaska, Elizabeth Muckersie, Cristina Martin-Granados, Maria Christofi, John V Forrester
Exposure of bone marrow derived dendritic cells (BMDC) to high dose ultrapure lipopolysaccharide for 24 hours (h) (LPS-primed BMDC) enhances their potency in preventing inter-photoreceptor retinoid binding protein (IRBP): complete Freund's adjuvant (CFA)-induced experimental autoimmune uveoretinitis (EAU). LPS-primed BMDC are refractory to further exposure to LPS (= endotoxin tolerance, ET), evidenced here by decreased phosphorylation of TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK) as well as impaired nuclear translocation of nuclear factor κB (NF-κB) and IRF3, resulting in reduced tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-12 and interferon beta (IFN-β) secretion...
November 15, 2016: Immunology
https://www.readbyqxmd.com/read/27861825/high-smad7-sustains-inflammatory-cytokine-response-in-refractory-celiac-disease
#5
Silvia Sedda, Veronica De Simone, Irene Marafini, Gerolamo Bevivino, Roberta Izzo, Omero Alessandro Paoluzi, Alfredo Colantoni, Angela Ortenzi, Paolo Giuffrida, Gino R Corazza, Alessandro Vanoli, Antonio Di Sabatino, Francesco Pallone, Giovanni Monteleone
Refractory celiac disease (RCD) is a form of celiac disease (CD) resistant to gluten-free diet and associated with elevated risk of complications. Many effector cytokines over-produced in the gut of RCD patients are supposed to amplify the tissue-destructive immune response, but it remains unclear if the RCD-associated mucosal inflammation is sustained by defects in counter-regulatory mechanisms. The aim of the present study was to determine whether RCD-related inflammation is marked by high Smad7, an intracellular inhibitor of transforming growth factor (TGF)-β1 activity...
November 14, 2016: Immunology
https://www.readbyqxmd.com/read/27859059/influence-of-e-coli-chaperone-dnak-on-protein-immunogenicity
#6
Kirsty D Ratanji, Jeremy P Derrick, Ian Kimber, Robin Thorpe, Meenu Wadhwa, Rebecca J Dearman
The production of anti-drug antibodies can impact significantly upon the safety and efficacy of biotherapeutics. It is known that various factors, including aggregation and the presence of process-related impurities can modify and augment the immunogenic potential of proteins. The purpose of the investigations reported here was to characterize in mice the influence of aggregation and host cell protein (HCP) impurities on the immunogenicity of a humanized single chain antibody variable fragment (scFv), and mouse albumin...
November 10, 2016: Immunology
https://www.readbyqxmd.com/read/27861835/distinct-t-helper-cell-dependence-of-memory-b-cell-proliferation-versus-plasma-cell-differentiation
#7
Franziska Zabel, Antonia Fettelschoss, Monique Vogel, Pal Johansen, Thomas M Kündig, Martin F Bachmann
Several memory B cell subclasses with distinct functions have been described of which the most effective is the class-switched (CS) memory B cell population. We have previously shown using virus-like particles (VLPs) that the proliferative potential of these CS memory B cells is limited and they fail to re-enter GCs. However, VLP specific memory B cells quickly differentiated into secondary plasma cells (PCs) with a virtue of elevated Ab production compared to primary PCs. Whereas the induction of VLP+ memory B cells was strongly dependent on Th, we were wondering whether re-stimulation of VLP+ memory B cells and their differentiation into secondary PCs would also require Th...
November 9, 2016: Immunology
https://www.readbyqxmd.com/read/27905107/co-operative-suppression-of-inflammatory-responses-in-human-dendritic-cells-by-plant-proanthocyanidins-and-products-from-the-parasitic-nematode-trichuris-suis
#8
Andrew R Williams, Elsenoor J Klaver, Lisa C Laan, Aina Ramsay, Christos Fryganas, Rolf Difborg, Helene Kringel, Jess D Reed, Irene Mueller-Harvey, Søren Skov, Irma van Die, Stig M Thamsborg
Interactions between dendritic cells (DCs) and environmental, dietary and pathogen antigens play a key role in immune homeostasis and regulation of inflammation. Dietary polyphenols such as proanthocyanidins (PAC) may reduce inflammation, and we therefore hypothesized that PAC may suppress lipopolysaccharide (LPS) -induced responses in human DCs and subsequent T helper type 1 (Th1) -type responses in naive T cells. Moreover, we proposed that, because DCs are likely to be exposed to multiple stimuli, the activity of PAC may synergise with other bioactive molecules that have anti-inflammatory activity, e...
November 7, 2016: Immunology
https://www.readbyqxmd.com/read/27891587/intestinal-mononuclear-cells-primed-by-systemic-interleukin-12-display-long-term-ability-to-aggravate-colitis-in-mice
#9
Luciano P Pedrotti, Angela A Sena, María Cecilia Rodriguez Galán, Hugo Cejas, Silvia G Correa
To address whether the burst of systemic interleukin-12 (IL-12) influences intestinal inflammation elicited by luminal stimuli, we induced IL-12 release by cDNA injection in C57BL/6 mice and simultaneously started dextran sulphate sodium administration. The sequence of the inflammatory response triggered by IL-12 release was characterized by assessing myeloperoxidase activity and histological damage in colon samples on days 1, 3, 5 and 7 after colitis induction. To evaluate the persistence of IL-12 priming, colitis was induced in mice 7 or 60 days after cDNA injection...
November 5, 2016: Immunology
https://www.readbyqxmd.com/read/27809352/t-bet-mediated-tim-3-expression-dampens-monocyte-function-during-chronic-hepatitis-c-virus-infection
#10
Wenjing Yi, Peixin Zhang, Yan Liang, Yun Zhou, Huanjun Shen, Chao Fan, Jonathan P Moorman, Zhi Q Yao, Zhansheng Jia, Ying Zhang
Hepatitis C virus (HCV) induces a high rate of chronic infection via dysregulation of host immunity. We have previously shown that T-cell immunoglobulin and mucin domain protein-3 (Tim-3) is up-regulated on monocyte/macrophages (M/MФ ) during chronic HCV infection; little is known, however, about the transcription factor that controls its expression in these cells. In this study, we investigated the transcription factor, T-box expressed in T cells (T-bet), on Tim-3 expression in M/MФ in the setting of HCV infection...
November 3, 2016: Immunology
https://www.readbyqxmd.com/read/27779741/deciphering-the-kir-system-at-super-resolution-for-nk-and-t-cell-biology
#11
REVIEW
Vivien Béziat, Hugo Hilton, Paul J Norman, James A Traherne
Killer-cell immunoglobulin-like receptors (KIRs) are components of two fundamental biological systems essential for human health and survival. Firstly, they contribute to host immune response, both innate and adaptive, through their expression by natural killer (NK) cells and T cells. Secondly, KIR play a key role in regulating placentation, and hence reproductive success. Analogous to the diversity of their HLA class I ligands, KIR are extremely polymorphic. In this review, we describe recent developments, fuelled by methodological advances, which are helping to decipher the KIR system in terms of haplotypes, polymorphisms, expression patterns and their ligand interactions...
October 25, 2016: Immunology
https://www.readbyqxmd.com/read/27779311/detrimental-effect-of-systemic-antimicrobial-cd4-t-cell-reactivity-on-gut-epithelial-integrity
#12
Cheong K C Kwong Chung, Francesca Ronchi, Markus B Geuking
Healthy host-microbial mutualism relies on compartmentalization and proper regulation of systemic and mucosal immune responses. Nevertheless, the systemic immune system is frequently exposed to bouts of bacteraemia, which can trigger systemic antimicrobial immune reactivity including CD4(+) T cells. Low level bacteraemia can occur when immune compartmentalization is compromised, for example in the presence of innate immune deficiency or following use of nonsteroidal anti-inflammatory drugs (NSAID). We generated an Escherichia coli strain expressing a defined T helper neo-epitope to study systemic antigen-specific antimicrobial CD4(+) T cells and their potential involvement in the pathogenicity of inflammatory bowel diseases (IBD)...
October 24, 2016: Immunology
https://www.readbyqxmd.com/read/27775159/a-dual-purpose-universal-influenza-vaccine-candidate-confers-protective-immunity-against-anthrax
#13
Maria T Arévalo, Junwei Li, Diana Diaz-Arévalo, Yanping Chen, Ashley Navarro, Lihong Wu, Yongyong Yan, Mingtao Zeng
Preventative influenza vaccines must be reformulated annually because of antigen shift and drift of circulating influenza viral strains. However, seasonal vaccines do not always match the circulating strains, and there is the ever-present threat that avian influenza viruses may adapt to humans. Hence, a universal influenza vaccine is needed to provide protective immunity against a broad range of influenza viruses. We designed an influenza antigen consisting of 3 tandem M2e repeats plus HA2, in combination with a detoxified anthrax edema toxin delivery system (EFn plus PA) to enhance immune responses...
October 24, 2016: Immunology
https://www.readbyqxmd.com/read/27763656/cd4-and-cd8-t-cell-immunity-to-dengue-lessons-for-the-study-of-zika-virus
#14
Laura Rivino, Mei Qiu Lim
Dengue (DENV) and Zika viruses (ZIKV) are rapidly emerging mosquito-borne flaviviruses which represent a public health concern. Understanding host protective immunity to these viruses is critical for the design of optimal vaccines. Over a decade of research has highlighted a significant contribution of the T cell response to both protection and/or disease enhancement during dengue infection, the latter being mainly associated with sub-optimal cross-reactive T cell responses during secondary infections. Phase IIb/III clinical trials of the first licensed tetravalent dengue vaccine highlight increased vaccine efficacy in dengue-immune as opposed to dengue-naïve vaccinees, suggesting a possible immunoprotective role of pre-existing DENV-specific T cells that are boosted upon vaccination...
October 20, 2016: Immunology
https://www.readbyqxmd.com/read/27753084/decline-of-mir-124-in-myeloid-cells-promotes-regulatory-t-cell-development-in-hepatitis-c-virus-infection
#15
Jun P Ren, Lin Wang, Juan Zhao, Ling Wang, Shun B Ning, Mohamed El Gazzar, Jonathan P Moorman, Zhi Q Yao
Myeloid-derived suppressor cells (MDSCs) and microRNAs (miRNAs) contribute to attenuating immune responses during chronic viral infection; however, the precise mechanisms underlying their suppressive activities remain incompletely understood. We have recently shown marked expansion of MDSCs that promote regulatory T (Treg) cell development in patients with chronic hepatitis C virus (HCV) infection. Here we further investigated whether the HCV-induced expansion of MDSCs and Treg cells is regulated by an miRNA-mediated mechanism...
October 18, 2016: Immunology
https://www.readbyqxmd.com/read/27716898/distinct-patterns-of-cytolytic-t-cell-activation-by-different-tumour-cells-revealed-by-ca-2-signalling-and-granule-mobilization
#16
Melissa Frick, Pierre Mouchacca, Grégory Verdeil, Yannick Hamon, Cyrille Billaudeau, Michel Buferne, Mathieu Fallet, Nathalie Auphan-Anezin, Anne-Marie Schmitt-Verhulst, Claude Boyer
Cancer-germline genes in both humans and mice have been shown to encode antigens susceptible to targeting by cytotoxic CD8 T effector cells (CTL). We analysed the ability of CTL to kill different tumour cell lines expressing the same cancer-germline gene P1A (Trap1a). We previously demonstrated that CTL expressing a T-cell receptor specific for the P1A35-43 peptide associated with H-2L(d) , although able to induce regression of P1A-expressing P815 mastocytoma cells, were much less effective against P1A-expressing melanoma cells...
October 7, 2016: Immunology
https://www.readbyqxmd.com/read/27709605/fungal-pattern-receptors-down-regulate-the-inflammatory-response-by-a-cross-inhibitory-mechanism-independent-of-il-10-production
#17
Mario Rodríguez, Saioa Márquez, Juan Vladimir de la Rosa, Sara Alonso, Antonio Castrillo, Mariano Sánchez Crespo, Nieves Fernández
CREB and STAT3 may control inflammation by several mechanisms, one of the best characterized is the induction of the expression of the anti-inflammatory cytokine IL-10. STAT3 also down-regulates the production of pro-inflammatory cytokines induced by ITAM-coupled receptors, a mechanism termed cross-inhibition. Because signaling via ITAM-dependent mechanisms is a hallmark of fungal pattern receptors, STAT3 activation might be involved in the cross-inhibition associated with invasive fungal infections. The fungal surrogate zymosan produced the phosphorylation of Y705-STAT3 and the expression of Ifnb1 and Socs3, but did not induce the IFN-signature cytokines Cxcl9 and Cxcl10 in BM-derived dendritic cells...
October 6, 2016: Immunology
https://www.readbyqxmd.com/read/27706808/understanding-the-regulation-of-pattern-recognition-receptors-in-inflammatory-diseases-a-nod-in-the-right-direction
#18
REVIEW
Claire L Feerick, Declan P McKernan
Nucleotide-binding oligomerization domain (NOD) -like receptors (NLRs) are a family of 23 receptors known as pattern recognition receptors; they are expressed in many cell types and play a key role in the innate immune response. The NLRs are activated by pathogen-associated molecular patterns, which include structurally conserved molecules present on the surfaces of bacteria. The activation of these NLRs by pathogens results in the downstream activation of signalling kinases and transcription factors, culminating in the transcription of genes coding for pro-inflammatory factors...
October 5, 2016: Immunology
https://www.readbyqxmd.com/read/27676456/induction-of-mucosal-immune-responses-against-helicobacter-pylori-infection-after-sublingual-and-intragastric-route-of-immunization
#19
Louise Sjökvist Ottsjö, Frida Jeverstam, Linda Yrlid, Alexander U Wenzel, Anna K Walduck, Sukanya Raghavan
There is a current lack of effective mucosal vaccines against major gastroenteric pathogens and particularly against Helicobacter pylori, a chronic infection that can lead to peptic ulcers and gastric cancer in a sub-population of infected individuals. Mucosal CD4(+) T cell responses have been shown to be essential for vaccine-induced protection against H. pylori infection. The current study addresses the influence of the adjuvant and site of mucosal immunization on early CD4(+) T cell priming to H. pylori antigens...
September 27, 2016: Immunology
https://www.readbyqxmd.com/read/27649685/elevated-systemic-glutamic-acid-level-in-the-non-obese-diabetic-mouse-is-idd-linked-and-induces-beta-cell-apoptosis
#20
Viqar Showkat Banday, Kristina Lejon
Although Type 1 diabetes (T1D) is T cell mediated disease in the effector stage, the mechanism behind the initial β cell assault less understood. Metabolomic differences, including elevated levels of glutamic acid, have been observed in T1D patients prior to disease onset, as well as in pre-diabetic non-obese diabetic (NOD) mice. Increased levels of glutamic acid damage both neurons and beta cells, implying that this could contribute to the initial events of T1D pathogenesis. We investigated the underlying genetic factors and consequences of the increased levels of glutamic acid in NOD...
September 21, 2016: Immunology
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