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Immune memory

Ming-Wei Lai, Kung-Hao Liang, Chau-Ting Yeh
OBJECTIVES: We aimed to investigate immunity against hepatitis B surface antigen (HBsAg) mutants before and after boosters in adolescents who lost antibodies against HBsAg (anti-HBs) despite neonatal vaccination. METHODS: We recruited 142 participants from 15 to 21 years old, who had received complete vaccination in infancy but became anti-HBs-negative. Cellular immunity to HBsAg and T-cell epitope variants was assessed before and after boosters. Antibody affinity to variants was assessed after boosters...
February 13, 2019: Clinical Microbiology and Infection
Fabrice Chimienti, Laurent Cavarec, Laurent Vincent, Nicolas Salvetat, Victoria Arango, Mark D Underwood, J John Mann, Jean-François Pujol, Dinah Weissmann
Phosphodiesterases (PDE) are key modulators of signal transduction and are involved in inflammatory cell activation, memory and cognition. There is a two-fold decrease in the expression of phosphodiesterase 8A (PDE8A) in the temporal cortex of major depressive disorder (MDD) patients. Here, we studied PDE8A mRNA-editing profile in two architectonically distinct neocortical regions in a clinically well-characterized cohort of age- and sex-matched non-psychiatric drug-free controls and depressed suicide decedents...
February 15, 2019: Translational Psychiatry
Dillon C Schrock, Scott A Leddon, Angela Hughson, Jim Miller, Adam Lacy-Hulbert, Deborah J Fowell
CD4+ follicular helper T cells (Tfh) are essential for germinal center (GC) reactions in the lymph node that generate high-affinity, long-lived plasma cells (LLPCs). Temporal GC analysis suggests B memory cells (Bmem) are generated early, while LLPCs are generated late in the GC reaction. Distinct roles for Tfh at these temporally different stages are not yet clear. Tfh entry into the GC is highly dynamic and the signals that maintain Tfh within the GC for support of late LLPC production are poorly understood...
February 15, 2019: Proceedings of the National Academy of Sciences of the United States of America
Hampartsoum B Barsoumian, Lalit Batra, Pradeep Shrestha, William S Bowen, Hong Zhao, Nejat K Egilmez, Jorge G Gomez-Gutierrez, Esma S Yolcu, Haval Shirwan
: Costimulation through 4-1BB (CD137) receptor generates robust CD8+ T-effector and memory responses. The only known ligand, 4-1BBL, is a trimeric transmembrane protein that has no costimulatory activity as a soluble molecule. Thus, agonistic antibodies to the receptor have been used for cancer immunotherapy in preclinical models and are currently being evaluated in the clinic. Here, we report that treatment with an oligomeric form of the ligand, SA-4-1BBL, as a single agent is able to protect mice against subsequent tumor challenge irrespective of the tumor type...
February 15, 2019: Cancer Research
Renée R C E Schreurs, Martin E Baumdick, Adrian F Sagebiel, Max Kaufmann, Michal Mokry, Paul L Klarenbeek, Nicola Schaltenberg, Fenja L Steinert, Jorik M van Rijn, Agata Drewniak, Sarah-May M L The, Roel Bakx, Joep P M Derikx, Niek de Vries, Willemijn E Corpeleijn, Steven T Pals, Nicola Gagliani, Manuel A Friese, Sabine Middendorp, Edward E S Nieuwenhuis, Konrad Reinshagen, Teunis B H Geijtenbeek, Johannes B van Goudoever, Madeleine J Bunders
Although the fetal immune system is considered tolerogenic, preterm infants can suffer from severe intestinal inflammation, including necrotizing enterocolitis (NEC). Here, we demonstrate that human fetal intestines predominantly contain tumor necrosis factor-α (TNF-α)+ CD4+ CD69+ T effector memory (Tem) cells. Single-cell RNA sequencing of fetal intestinal CD4+ T cells showed a T helper 1 phenotype and expression of genes mediating epithelial growth and cell cycling. Organoid co-cultures revealed a dose-dependent, TNF-α-mediated effect of fetal intestinal CD4+ T cells on intestinal stem cell (ISC) development, in which low T cell numbers supported epithelial development, whereas high numbers abrogated ISC proliferation...
February 5, 2019: Immunity
Timo Vesikari, Lars Østergaard, Johannes Beeslaar, Judith Absalon, Joseph J Eiden, Kathrin U Jansen, Thomas R Jones, Shannon L Harris, Roger Maansson, Samantha Munson, Robert E O'Neill, Laura J York, John L Perez
BACKGROUND: The period of heightened risk of invasive meningococcal disease in adolescence extends for >10 years. This study aimed to evaluate persistence of the immune response to the serogroup B meningococcal (MenB) vaccine MenB-FHbp (Trumenba® , Bivalent rLP2086) under two- and three-dose primary vaccination schedules, both of which are approved in the United States and the European Union, and to assess safety and immunogenicity of a booster dose. METHODS: This was an open-label extension study of a phase 2 randomized MenB-FHbp study (primary study)...
February 12, 2019: Vaccine
Richard K Tennant, Barbara Holzer, John Love, Elma Tchilian, Harry N White
Designing improved vaccines against mutable viruses such as Dengue and Influenza would be helped by a better understanding of how the B-cell memory compartment responds to variant antigens. Towards this we have recently shown after secondary immunization of mice with a widely variant Dengue envelope protein, with only 63% amino-acid identity, that IgM+ memory B-cells with few mutations supported an efficient secondary germinal centre (GC) and serum response, superior to a primary response to the same protein...
February 15, 2019: Immunology
Xiang-Bo Ji, Jun Luo, Xiu-Li Feng, Qiu-Liang Xu, Teng Man, Dong Zhao, Xin-Feng Li, Gai-Ping Zhang, Pu-Yan Chen
Background: In the recent past, many studies have been focused on extracts of BF and multiple biologically active factors and their effects on humoral immune system in chickens and birds. However, the mechanism of those immunomodulatory peptides on the B lineage cells proliferation and antibody production in chicken is fairly unknown. DT40 cell line, an avian leucosis virus-induced chicken pre-B cell line, expresses immunoglobulin M (IgM) isotype B cell reporter in the plasma membrane...
December 2018: African Health Sciences
Robin Graf, Jane Seagal, Kevin L Otipoby, Kong-Peng Lam, Salah Ayoub, Baochun Zhang, Sandrine Sander, Van Trung Chu, Klaus Rajewsky
B2 cells engage in classical antibody responses, whereas B1 cells are considered carriers of innate immunity, biased toward recognizing epitopes present on the surfaces of common pathogens and self antigens. To explore the role of B cell antigen receptor (BCR) specificity in driving B1 cell differentiation, we developed a transgenic system allowing us to change BCR specificity in B cells in an inducible and programmed manner. Mature B2 cells differentiated into bona fide B1 cells upon acquisition of a B1 cell-typical self-reactive BCR through a phase of proliferative expansion...
February 15, 2019: Science
Maud Plantinga, Colin G de Haar, Ester Dünnebach, Denise A M H van den Beemt, Kitty W M Bloemenkamp, Michal Mokry, Jaap Jan Boelens, Stefan Nierkens
Dendritic cells (DCs) are professional antigen-presenting cells which instruct both the innate and adaptive immune systems. Once mature, they have the capacity to activate and prime naïve T cells for recognition and eradication of pathogens and tumor cells. These characteristics make them excellent candidates for vaccination strategies. Most DC vaccines have been generated from ex vivo culture of monocytes (mo). The use of mo-DCs as vaccines to induce adaptive immunity against cancer has resulted in clinical responses but, overall, treatment success is limited...
February 5, 2019: Cancers
Sujeenthar Tharmalingam, Shayenthiran Sreetharan, Antone L Brooks, Douglas R Boreham
The linear no-threshold (LNT) model is currently used to estimate low dose radiation (LDR) induced health risks. This model lacks safety thresholds and postulates that health risks caused by ionizing radiation is directly proportional to dose. Therefore even the smallest radiation dose has the potential to cause an increase in cancer risk. Advances in LDR biology and cell molecular techniques demonstrate that the LNT model does not appropriately reflect the biology or the health effects at the low dose range...
November 29, 2018: Chemico-biological Interactions
Matteo Basilissi, Camilla Tincati, Esther Merlini, Giuseppe Ancona, Elisa Borghi, Francesca Borgo, Alessandra Barassi, Antonella d'Arminio Monforte, Giulia Marchetti
HIV infection causes the progressive depletion of CD4+ T-lymphocytes and profound modifications of T-cell homeostasis, which persist despite virologically-suppressive treatment and have been linked to a worse clinical outcome. Enduring alterations of the gastrointestinal tract may represent the underlying pathogenic mechanisms of these phenomena. Twenty-six HIV-infected subjects were assessed over a 12-month period following the introduction of antiretroviral therapy. 18 uninfected individuals were enrolled as controls...
2019: PloS One
Shahram Barfi, Vahdat Poortahmasebi, Haleh Ofoghi, Mohammad Farahmand, Saeid Ghorbani, Mehdi Norouzi, Leila Ghalichi, Seyed Mohammad Jazayeri
BACKGROUND: Responsiveness to hepatitis B vaccine among Autism Spectrum Disorders (ASD) patients has not been evaluated worldwide. We aimed to determine the anti-HBs antibody duration in autistic and healthy children few years after primary vaccination and evaluate their immunological memory against Hepatitis B virus (HBV( vaccine with booster dose administration. METHODS: 107 and 147 HBsAg-negative children from ASD and normal population were recruited, respectively...
February 13, 2019: Journal of Medical Virology
Felix Broecker, Karin Moelling
Virus-derived sequences and transposable elements constitute a substantial portion of many cellular genomes. Recent insights reveal the intimate evolutionary relationship between these sequences and various cellular immune pathways. At the most basic level, superinfection exclusion may be considered a prototypical virus-mediated immune system that has been described in both prokaryotes and eukaryotes. More complex immune mechanisms fully or partially derived from mobile genetic elements include CRISPR-Cas of prokaryotes and the RAG1/2 system of vertebrates, which provide immunological memory of foreign genetic elements and generate antibody and T cell receptor diversity, respectively...
2019: Frontiers in Microbiology
Lori McGinnes Cullen, Madelyn R Schmidt, Trudy G Morrison
Most individuals are infected with respiratory syncytial virus (RSV) by age two, but infection does not result in long-term protective immunity to subsequent infections. Previous RSV infection may, however, impact responses to an RSV vaccine. The goal of these studies was to explore the effect of previous RSV infection on murine antibody responses to RSV F and G protein containing virus-like particles (VLP), comparing responses to those resulting from VLP immunization of RSV naïve animals. These studies showed that after RSV infection, immunization with a single dose of VLPs containing a conformation stabilized pre-fusion F protein stimulated high titers of neutralizing antibodies (NA) while an immunization with post-F containing VLPs or a second RSV infection only weakly stimulated NA even though total anti-F protein IgG antibody levels in both VLP immunized animals were similar...
February 13, 2019: Journal of Virology
Geraldine Blanchard Rohner, Olga Chatzis, Pailinrut Chinwangso, Marie Rohr, Stéphane Grillet, Carole Salomon, Barbara Lemaître, Pitchaya Boonrak, Saranath Lawpoolsri, Elizabeth Clutterbuck, Indrajeet Kumar Poredi, Wassana Wijagkanalan, Jane Spiegel, Hong Thai Pham, Simonetta Viviani, Claire-Anne Siegrist
Background: Protection induced by acellular pertussis (aP) vaccines is partial and short-lived, especially in teenagers, calling for novel immunization strategies. Methods: We conducted an investigator-driven proof-of-concept randomized controlled trial in aP-primed adolescents in Geneva to assess the immunogenicity and reactogenicity of a novel recombinant aP (r-aP) vaccine including recombinant pertussis toxin (PT) and filamentous hemagglutinin (FHA) coadministered with tetanus-diphtheria toxoids (Td), compared to a licensed tetanus-diphtheria-aP vaccine containing chemically detoxified PT (cd/Tdap)...
July 26, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Zebin Wang, Kaiming Sun, Yonghong Xiao, Bin Feng, Keith Mikule, XiaoYan Ma, Ningping Feng, Christopher P Vellano, Lorenzo Federico, Joseph R Marszalek, Gordon B Mills, Jeffrey Hanke, Sridhar Ramaswamy, Jing Wang
PARP inhibitors have been proven clinically efficacious in platinum-responsive ovarian cancer regardless of BRCA1/2 status and in breast cancers with germline BRCA1/2 mutation. However, resistance to PARP inhibitors may preexist or evolve during treatment in many cancer types and may be overcome by combining PARP inhibitors with other therapies, such as immune checkpoint inhibitors, which confer durable responses and are rapidly becoming the standard of care for multiple tumor types. This study investigated the therapeutic potential of combining niraparib, a highly selective PARP1/2 inhibitor, with anti-PD-1 immune checkpoint inhibitors in preclinical tumor models...
February 12, 2019: Scientific Reports
Maxence Ernoult, Julie Grollier, Damien Querlioz
One of the biggest stakes in nanoelectronics today is to meet the needs of Artificial Intelligence by designing hardware neural networks which, by fusing computation and memory, process and learn from data with limited energy. For this purpose, memristive devices are excellent candidates to emulate synapses. A challenge, however, is to map existing learning algorithms onto a chip: for a physical implementation, a learning rule should ideally be tolerant to the typical intrinsic imperfections of such memristive devices, and local...
February 12, 2019: Scientific Reports
Hong-Gyun Lee, Jae-Ung Lee, Do-Hyun Kim, Sangho Lim, Insoo Kang, Je-Min Choi
T cells generate antigen-specific immune responses to their cognate antigen as a hallmark of adaptive immunity. Despite the importance of antigen-specific T cells, here we show that antigen non-related, bystander memory-like CD4+ T cells also significantly contribute to autoimmune pathogenesis. Transcriptome analysis demonstrates that interleukin (IL)-1β- and IL-23-prime T cells that express pathogenic TΗ 17 signature genes such as RORγt, CCR6, and granulocyte macrophage colony-stimulating factor (GM-CSF)...
February 12, 2019: Nature Communications
A M Heeren, J Rotman, A G M Stam, N Pocorni, A A Gassama, S Samuels, M C G Bleeker, C H Mom, H J M A A Zijlmans, G G Kenter, E S Jordanova, T D de Gruijl
BACKGROUND: Cervical cancer (CxCa) is mainly a locally invading disease that metastasizes to loco-regional lymph node basins before involving distant organs in more advanced stages. Local immune potentiation of tumor-draining lymph nodes (TDLN) may thus protect against tumor progression. METHODS: To identify therapeutic targets for local immune modulation, multi-parameter flow cytometric T-cell profiling of primary cervical tumors (PT) and TDLN (n = 37) was performed...
February 12, 2019: Journal for Immunotherapy of Cancer
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