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Immunological reconstitution

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https://www.readbyqxmd.com/read/28303782/paradoxical-reactions-and-the-immune-reconstitution-inflammatory-syndrome
#1
L W Preston Church, Amit Chopra, Marc A Judson
In HIV-infected individuals, paradoxical reactions after the initiation of antiretroviral therapy (ART) are associated with a variety of underlying infections and have been called the immune reconstitution inflammatory syndrome (IRIS). In cases of IRIS associated with tuberculosis (TB), two distinct patterns of disease are recognized: (i) the progression of subclinical TB to clinical disease after the initiation of ART, referred to as unmasking, and (ii) the progression or appearance of new clinical and/or radiographic disease in patients with previously recognized TB after the initiation of ART, the classic or "paradoxical" TB-IRIS...
March 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28296255/breg-dependent-islet-transplant-tolerance-is-also-nk-cell-dependent
#2
Christian Schuetz, Kang Mi Lee, Ryan Scott, Lisa Kojima, Laura Washburn, Liye Liu, Wei-Hui Liu, Haley Tector, Ji Lei, Heidi Yeh, James Kim, James F Markmann
Immunologic tolerance to solid organ and islet cell grafts has been achieved in various rodent models using antibodies directed at CD45RB and Tim-1. We have shown that this form of tolerance depends on regulatory B-cells. To elucidate further the mechanism by which Bregs induce tolerance we investigated the requirement of NK and NKT cells in this model. To do so, hyperglycemic B6, μMT, Beige or CD1d(-/-) mice received Balb/c islet grafts and treatment with the tolerance inducing regimen consisting of anti-CD45RB and anti -TIM1...
March 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28290451/development-of-sh2-probes-and-pull-down-assays-to-detect-pathogen-induced-site-specific-tyrosine-phosphorylation-of-the-tlr-adaptor-scimp
#3
Lin Luo, Samuel J Tong, Adam A Wall, Tatiana Khromykh, Matthew J Sweet, Jennifer L Stow
Protein tyrosine phosphorylation guides many molecular interactions for cellular functions. SCIMP is a transmembrane adaptor protein (TRAP) family member that mediates selective proinflammatory cytokine responses generated by pathogen-activated Toll-like receptor (TLR) pathways in macrophages. TLR activation triggers SCIMP phosphorylation and selective phosphorylation of distinct tyrosine residues on this adaptor offers the potential for regulating or biasing inflammatory responses. To analyze site-specific phosphorylation events, we developed three probes based on the SH2 domains of known SCIMP effectors, and used them for pull-downs from macrophage extracts...
March 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28277827/progress-and-prospects-for-the-use-and-the-understanding-of-the-mode-of-action-of-autologous-hematopoietic-stem-cell-transplantation-in-the-treatment-of-multiple-sclerosis
#4
Fredrika Collins, Majid Kazmi, Paolo A Muraro
A substantial proportion of patients with multiple sclerosis (MS) do not respond to pharmacological treatments and no currently approved therapy has been convincingly demonstrated to prevent or stop disease progression. With MS widely believed to be an auto-immune disease, immunoablative therapy followed by autologous haematopoietic stem cell transplantation (I/AHSCT) is being investigated as an alternative therapeutic option. Areas covered: With the results of phase III comparative trials only a few years away, this article reviews animal and clinical trials of I/AHSCT in the treatment of MS and discusses possible immunological mechanisms behind its action...
March 20, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28275376/immunological-balance-is-associated-with-clinical-outcome-after-autologous-hematopoietic-stem-cell-transplantation-in-type-1-diabetes
#5
Kelen C R Malmegrim, Júlia T C de Azevedo, Lucas C M Arruda, Joana R F Abreu, Carlos E B Couri, Gislane L V de Oliveira, Patricia V B Palma, Gabriela T Scortegagna, Ana B P L Stracieri, Daniela A Moraes, Juliana B E Dias, Fabiano Pieroni, Renato Cunha, Luiza Guilherme, Nathália M Santos, Milton C Foss, Dimas T Covas, Richard K Burt, Belinda P Simões, Júlio C Voltarelli, Bart O Roep, Maria C Oliveira
Autologous hematopoietic stem cell transplantation (AHSCT) increases C-peptide levels and induces insulin independence in patients with type 1 diabetes. This study aimed to investigate how clinical outcomes may associate with the immunological status, especially concerning the balance between immunoregulation and autoreactivity. Twenty-one type 1 diabetes patients were monitored after AHSCT and assessed every 6 months for duration of insulin independence, C-peptide levels, frequencies of islet-specific autoreactive CD8(+) T cells (CTL), regulatory lymphocyte subsets, thymic function, and T-cell repertoire diversity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28255719/a-protein-expression-toolkit-for-studying-signaling-in-t-cells
#6
Ana Mafalda Santos, Jiandong Huo, Deborah Hatherley, Mami Chirifu, Simon J Davis
Innate and adaptive cellular immunity is dependent on interactions of cell surface receptors that initiate signaling, resulting in the formation of the immunological synapse and targeted delivery of effector functions. There has been considerable interest over the past 30 years in methods for isolating the extracellular regions of these receptors and components of the cytoplasmic signaling networks. This chapter describes our current protein expression toolkit used for structural studies of signaling proteins and the functional reconstitution of model cell surfaces, which comprises both bacterial and mammalian cell-based protein expression methodologies...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28255717/comprehensive-analysis-of-immunological-synapse-phenotypes-using-supported-lipid-bilayers
#7
Salvatore Valvo, Viveka Mayya, Elena Seraia, Jehan Afrose, Hila Novak-Kotzer, Daniel Ebner, Michael L Dustin
Supported lipid bilayers (SLB) formed on glass substrates have been a useful tool for study of immune cell signaling since the early 1980s. The mobility of lipid-anchored proteins in the system, first described for antibodies binding to synthetic phospholipid head groups, allows for the measurement of two-dimensional binding reactions and signaling processes in a single imaging plane over time or for fixed samples. The fragility of SLB and the challenges of building and validating individual substrates limit most experimenters to ~10 samples per day, perhaps increasing this few-fold when examining fixed samples...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28255705/f%C3%A3-rster-resonance-energy-transfer-to-study-tcr-pmhc-interactions-in-the-immunological-synapse
#8
Gerhard J Schütz, Johannes B Huppa
T-cell antigen recognition is remarkably efficient: when scanning the surface of antigen-presenting cells (APCs), T-cells can detect the presence of just a few single antigenic peptide/MHCs (pMHCs), which are often vastly outnumbered by structurally similar non-stimulatory endogenous pMHCs (Irvine et al., Nature 419(6909):845-849, 2002; Purbhoo et al., Nat Immunol 5(5):524-530, 2004; Huang et al., Immunity 39(5):846-857, 2013). How T-cells achieve this is still enigmatic, in particular in view of the rather moderate affinity that TCRs typically exert for antigenic pMHCs, at least when measured in vitro (Davis et al...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28210842/uric-acid-as-a-novel-biomarker-for-bone-marrow-function-and-incipient-hematopoietic-reconstitution-after-aplasia-in-patients-with-hematologic-malignancies
#9
Sebastian P Haen, Vicky Eyb, Nora Mirza, Aline Naumann, Andreas Peter, Markus W Löffler, Christoph Faul, Wichard Vogel, Wolfgang A Bethge, Hans-Georg Rammensee, Lothar Kanz, Martin Heni
PURPOSE: Prolonged aplasia and graft failure (GF) represent life-threatening complications after hematopoietic cell transplantation (HCT) requiring suitable biomarkers for early detection and differentiation between GF and poor graft function (PGF). Uric acid (UA) is a strong immunological danger signal. METHODS: Laboratory results were analyzed from patients undergoing either allogeneic or autologous HCT or induction chemotherapy for acute leukemia (n = 50 per group, n = 150 total)...
February 16, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28209523/tb-iris-proteomic-analysis-of-in-vitro-pbmc-responses-to-mycobacterium-tuberculosis-and-response-modulation-by-dexamethasone
#10
Liam Bell, Janique M Peyper, Shaun Garnett, Rabecca Tadokera, Robert Wilkinson, Graeme Meintjes, Jonathan M Blackburn
Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) occurs in 8-54% of South African patients undergoing treatment for tuberculosis/human immunodeficiency virus co-infection. Improved TB-IRIS molecular pathogenesis understanding would enhance risk stratification, diagnosis, prognostication, and treatment. We assessed how TB-IRIS status and dexamethasone influence leukocyte proteomic responses to Mycobacterium tuberculosis (Mtb). Patient blood was obtained three weeks post-anti-retroviral therapy initiation...
February 14, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28183335/efficacy-of-vitamin-d3-supplementation-in-reducing-incidence-of-pulmonary-tuberculosis-and-mortality-among-hiv-infected-tanzanian-adults-initiating-antiretroviral-therapy-study-protocol-for-a-randomized-controlled-trial
#11
Christopher R Sudfeld, Ferdinand Mugusi, Said Aboud, Tumaini J Nagu, Molin Wang, Wafaie W Fawzi
BACKGROUND: HIV-infected adults initiating antiretroviral therapy (ART) in sub-Saharan Africa continue to experience high rates of morbidity and mortality during the initial months of treatment. Observational studies in high-income and resource-limited settings indicate that HIV-infected adults with low vitamin D levels may be at increased risk of mortality, HIV disease progression, and incidence of pulmonary tuberculosis (TB). As a result, vitamin D3 supplementation may improve survival and treatment outcomes for HIV-infected adults initiating ART...
February 10, 2017: Trials
https://www.readbyqxmd.com/read/28176791/il-36%C3%AE-is-a-crucial-proximal-component-of-protective-type-1-mediated-lung-mucosal-immunity-in-gram-positive-and-negative-bacterial-pneumonia
#12
M A Kovach, B Singer, G Martinez-Colon, M W Newstead, X Zeng, P Mancuso, T A Moore, S L Kunkel, M Peters-Golden, B B Moore, T J Standiford
Interleukin-36γ (IL-36γ) is a member of novel IL-1-like proinflammatory cytokine family that are highly expressed in epithelial tissues and several myeloid-derived cell types. Little is known about the role of the IL-36 family in mucosal immunity, including lung anti-bacterial responses. We used murine models of IL-36γ deficiency to assess the contribution of IL-36γ in the lung during experimental pneumonia. Induction of IL-36γ was observed in the lung in response to Streptococcus pneumoniae (Sp) infection, and mature IL-36γ protein was secreted primarily in microparticles...
February 8, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28176790/architectural-and-functional-alterations-of-the-small-intestinal-mucosa-in-classical-whipple-s-disease
#13
H-J Epple, J Friebel, V Moos, H Troeger, S M Krug, K Allers, K Schinnerling, A Fromm, B Siegmund, M Fromm, J D Schulzke, T Schneider
Classical Whipple's disease (CWD) affects the gastrointestinal tract and rather elicits regulatory than inflammatory immune reactions. Mechanisms of malabsorption, diarrhea, and systemic immune activation are unknown. We here analyzed mucosal architecture, barrier function, and immune activation as potential diarrheal trigger in specimens from 52 CWD patients. Our data demonstrate villus atrophy and crypt hyperplasia associated with epithelial apoptosis and reduced alkaline phosphatase expression in the duodenum of CWD patients...
February 8, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28106477/thymosin-alpha-1-and-hiv-1-recent-advances-and-future-perspectives
#14
Claudia Matteucci, Sandro Grelli, Emanuela Balestrieri, Antonella Minutolo, Ayele Argaw-Denboba, Beatrice Macchi, Paola Sinibaldi-Vallebona, Carlo Federico Perno, Antonio Mastino, Enrico Garaci
In spite of the consistent benefits for HIV-1 infected patients undergoing antiretroviral therapy, a complete immune reconstitution is usually not achieved. Actually, antiretroviral therapy may be frequently accompanied by immunological unresponsiveness, persistent inflammatory conditions and inefficient cytotoxic T-cell response. Thymosin alpha 1 is a thymic peptide that demonstrates a peculiar ability to restore immune system homeostasis in different physiological and pathological conditions (i.e., infections, cancer, immunodeficiency, vaccination and aging) acting as multitasking protein depending on the host state of inflammation or immune dysfunction...
January 20, 2017: Future Microbiology
https://www.readbyqxmd.com/read/28103947/long-term-immune-reconstitution-and-t-cell-repertoire-analysis-after-autologous-hematopoietic-stem-cell-transplantation-in-systemic-sclerosis-patients
#15
Dominique Farge, Lucas C M Arruda, Fanny Brigant, Emmanuel Clave, Corinne Douay, Zora Marjanovic, Christophe Deligny, Guitta Maki, Eliane Gluckman, Antoine Toubert, Helene Moins-Teisserenc
The determinants of clinical responses after autologous hematopoietic stem cell transplantation (aHSCT) in systemic sclerosis (SSc) are still unraveled. We analyzed long-term immune reconstitution (IR) and T cell receptor (TCR) repertoire diversity in 10 SSc patients, with at least 6 years simultaneous clinical and immunological follow-up after aHSCT. Patients were retrospectively classified as long-term responders (A, n = 5) or non-responders (B, n = 5), using modified Rodnan's skin score (mRSS) and forced vital capacity (FVC%)...
January 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28098596/erythema-nodosum-leprosum-like-lesions-are-a-histopathologic-pattern-in-whipple-s-disease-and-a-sign-of-the-immune-reconstitution-inflammatory-syndrome-a-case-series-and-review-of-the-literature
#16
Julia Liersch, Agnès Carlotti, Anne Theunis, Alexandra Leonard, Mary Barrett, John Andrew Carlson, Jörg Schaller
Inflammatory and subcutaneous nodules can arise in treated and untreated cases of Whipple disease (WD). The inflammatory immune reconstitution syndrome describes paradoxical clinical inflammatory worsening of a preexisting condition because of a return of immune function. Clinicopathologic examination of 4 patients with WD who presented with erythema nodosum leprosum (ENL)-like lesions and the findings of a systematic review of this phenomenon revealed that ENL-like lesions occurred in predominantly middle-aged male patients who suffered from WD, mostly on the legs...
April 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28086758/toxoplasmosis-associated-iris-involving-the-cns-a-case-report-with-longitudinal-analysis-of-t-cell-subsets
#17
Rita Rb-Silva, Claudia Nobrega, Eugénia Reiriz, Soraia Almeida, Rui Sarmento-Castro, Margarida Correia-Neves, Ana Horta
BACKGROUND: HIV-infected patients may present an unforeseen clinical worsening after initiating antiretroviral therapy known as immune reconstitution inflammatory syndrome (IRIS). This syndrome is characterized by a heightened inflammatory response toward infectious or non-infectious triggers, and it may affect different organs. Diagnosis of IRIS involving the central nervous system (CNS-IRIS) is challenging due to heterogeneous manifestations, absence of biomarkers to identify this condition, risk of long-term sequelae and high mortality...
January 13, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28079818/factors-associated-with-syphilis-incidence-in-the-hiv-infected-in-the-era-of-highly-active-antiretrovirals
#18
Mohaned Shilaih, Alex Marzel, Dominique L Braun, Alexandra U Scherrer, Helen Kovari, Jim Young, Alexandra Calmy, Katharine Darling, Manuel Battegay, Matthias Hoffmann, Enos Bernasconi, Maria C Thurnheer, Huldrych F Günthard, Roger D Kouyos
After several years of steady decline, syphilis is reemerging globally as a public health hazard, especially among people living with human immunodeficiency virus (HIV). Syphilis resurgence is observed mainly in men who have sex with men (MSM), yet other transmission groups are affected too. In this manuscript, we study the factors associated with syphilis incidence in the Swiss HIV cohort study in the era of highly effective antiretrovirals. Using parametric interval censored models with fixed and time-varying covariates, we studied the immunological, behavioral, and treatment-related elements associated with syphilis incidence in 3 transmission groups: MSM, heterosexuals, and intravenous drug users...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28057639/clinical-and-immunologic-impact-of-ccr5-blockade-in-graft-versus-host-disease-prophylaxis
#19
Ryan H Moy, Austin P Huffman, Lee P Richman, Lisa Crisalli, Ximi K Wang, James A Hoxie, Rosemarie Mick, Stephen G Emerson, Yi Zhang, Robert H Vonderheide, David L Porter, Ran Reshef
Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Lymphocyte trafficking via chemokine receptors such as CCR5 plays a critical role in alloreactive responses, and previous data suggest that CCR5 blockade with maraviroc results in a low incidence of visceral GVHD. However, the full scope of clinical and immunologic effects of CCR5 blockade in HSCT has not been described. We compared a cohort of patients enrolled on a trial of reduced-intensity allo-HSCT with standard GVHD prophylaxis plus maraviroc to a contemporary control cohort receiving standard GVHD prophylaxis alone...
February 16, 2017: Blood
https://www.readbyqxmd.com/read/28018346/low-double-negative-cd3-cd4-cd8-t-cells-are-associated-with-incomplete-restoration-of-cd4-t-cells-and-higher-immune-activation-in-hiv-1-immunological-non-responders
#20
Xiaofan Lu, Bin Su, Huan Xia, Xin Zhang, Zhiying Liu, Yunxia Ji, Zixuan Yang, Lili Dai, Luzia M Mayr, Christiane Moog, Hao Wu, Xiaojie Huang, Tong Zhang
Failure of immune reconstitution increases the risk of AIDS or non-AIDS related morbidity and mortality in HIV-1-infected patients. CD3(+)CD4(-)CD8(-) T cells, which are usually described as double-negative (DN) T cells, display CD4-like helper and immunoregulatory functions. Here, we have measured the percentage of DN T cells in the immune reconstituted vs. non-immune reconstituted HIV-1-infected individuals. We observed that immunological non-responders (INRs) had a low number of DN T cells after long-term antiretroviral therapy (ART), and the number of these cells positively correlated with the CD4(+) T cell count...
2016: Frontiers in Immunology
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