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Immune memory

Carine Claeys, Vijayalakshmi Chandrasekaran, José García-Sicilia, Roman Prymula, Javier Díez-Domingo, Jerzy Brzostek, Josep Marès-Bermúdez, Federico Martinón-Torres, Andrew J Pollard, Renata Růžková, Alfonso Carmona Martinez, Angels Ulied, Mariano Miranda Valdivieso, Saul N Faust, Matthew D Snape, Damien Friel, Thierry Ollinger, Jyoti Soni, Anne Schuind, Ping Li, Bruce L Innis, Varsha K Jain
BACKGROUND: It has not yet been demonstrated whether two doses of inactivated quadrivalent influenza vaccine (IIV4) prime a booster response in infants. We evaluated the anamnestic immune response to an IIV4 in children aged 17-48 months. METHODS: Children were randomized to two doses of IIV4 or control in the primary phase III study (NCT01439360). One year later, in an open-label revaccination extension study (NCT01702454), a subset of children who received IIV4 in the primary study (primed group) received one IIV4 dose and children who received control in the primary study (unprimed) received two IIV4 doses 28 days apart...
October 15, 2018: Pediatric Infectious Disease Journal
Nicholas A Zwang, Balaji B Ganesh, Kim T Cardenas, Anita S Chong, Patricia W Finn, David L Perkins
BACKGROUND AND PURPOSE: Phospho flow cytometry is a powerful technique to analyze signaling in rare cell populations. This technique, however, requires harsh conditions for cell fixation and permeabilization, which can denature surface antigens or antibody-conjugated fluorochromes. These are among several technical limitations which have been a barrier to quantify signaling in unique B cell subsets. One such immature subset, transitional B cells (TrBs), may play a role in suppressing solid organ transplant rejection, graft-versus-host disease, autoimmunity, and even the immune response to malignancy...
October 12, 2018: Journal of Immunological Methods
Xinpeng Jiang, Shuang Xia, Xinmiao He, Hong Ma, Yanzhong Feng, Ziguang Liu, Wentao Wang, Ming Tian, Heshu Chen, Fugang Peng, Liang Wang, Peng Zhao, Junwei Ge, Di Liu
Enterotoxigenic Escherichia coli (ETEC) remains a massive burden in developing countries with increasing morbidity and mortality rates; it is also an important pathogen in the farming industry and is a leading cause of bacterial diarrhea. Our previous study showed that nanometer-sized inclusion bodies (IBs) of the fimbrial adhesin subunit protein (FaeG), mutation heat-stable enterotoxin a (mSTa), heat-labile enterotoxin b (LTb), and STb (nontargeting) fusion protein as an oral vaccine induced both systemic and mucosal immune responses...
October 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Ashley L Fink, Sabra L Klein
Males and females differ in their effector and memory immune responses to foreign and self-antigens. The difference in antibody responses (i.e., humoral immunity), in particular, is one of the most well conserved sex differences in immunology. Certain sex differences in humoral immunity are present throughout life, whereas others are only apparent after puberty and prior to reproductive senescence, suggesting that both genes and hormones are involved. Importantly, these sex-based differences in humoral immunity contribute to variation in the responses to vaccines and may explain some disparities in vaccine efficacy between the sexes...
December 2018: Current Opinion in Physiology
Laura Antonio-Herrera, Oscar Badillo-Godinez, Oscar Medina-Contreras, Araceli Tepale-Segura, Alberto García-Lozano, Lourdes Gutierrez-Xicotencatl, Gloria Soldevila, Fernando R Esquivel-Guadarrama, Juliana Idoyaga, Laura C Bonifaz
CD4+ T cells are major players in the immune response against several diseases; including AIDS, leishmaniasis, tuberculosis, influenza and cancer. Their activation has been successfully achieved by administering antigen coupled with antibodies, against DC-specific receptors in combination with adjuvants. Unfortunately, most of the adjuvants used so far in experimental models are unsuitable for human use. Therefore, human DC-targeted vaccination awaits the description of potent, yet nontoxic adjuvants. The nontoxic cholera B subunit (CTB) can be safely used in humans and it has the potential to activate CD4+ T cell responses...
2018: Frontiers in Immunology
Federica Costa, Rituparna Das, Jithendra Kini Bailur, Kavita Dhodapkar, Madhav V Dhodapkar
Despite major improvements in the treatment landscape, most multiple myeloma (MM) patients eventually succumb to the underlying malignancy. Immunotherapy represents an attractive strategy to achieve durable remissions due to its specificity and capacity for long term memory. Activation of immune cells is controlled by a balance of agonistic and inhibitory signals via surface and intracellular receptors. Blockade of such inhibitory immune receptors (termed as "immune checkpoints") including PD-1/PD-L1 has led to impressive tumor regressions in several cancers...
2018: Frontiers in Immunology
Elise V Mike, Hadijat M Makinde, Evan Der, Ariel Stock, Maria Gulinello, Gaurav T Gadhvi, Deborah R Winter, Carla M Cuda, Chaim Putterman
About 40% of patients with systemic lupus erythematosus experience diffuse neuropsychiatric manifestations, including impaired cognition and depression. Although the pathogenesis of diffuse neuropsychiatric SLE (NPSLE) is not fully understood, loss of brain barrier integrity, autoreactive antibodies, and pro-inflammatory cytokines are major contributors to disease development. Fingolimod, a sphingosine-1-phosphate (S1P) receptor modulator, prevents lymphocyte egress from lymphoid organs through functional antagonism of S1P receptors...
2018: Frontiers in Immunology
Beatriz Díaz-Molina, Paula Diaz-Bulnes, Reyes Carvajal Palao, Maria José Bernardo, Ramón M Rodriguez, Viviana Corte-Iglesias, Cesar Moris de la Tassa, Jose Luis Lambert, Beatriz Suarez-Alvarez
The positive long-term effects of conversion to everolimus (EVL) after heart transplantation (HT) have been evaluated in several studies. However, the timing of EVL initiation, the best way to combine it with other immunosuppressive treatments, and the impact of these combinations on the immune response are poorly understood aspects. Here, we analyzed the immune phenotype and function of HT patients ( n = 56) at short and long terms (prospective and retrospective cohorts), taking into account the time of EVL initiation: early (3 months post-transplant, EVL-E group) or late (>1 year post-transplant, EVL-L group) compared with mycophenolate mofetil treatment (MMF group)...
2018: Frontiers in Immunology
Heejung Chun, Ian Marriott, C Justin Lee, Hansang Cho
Alzheimer's disease (AD) is an irreversible neurodegenerative illness and the exact etiology of the disease remains unknown. It is characterized by long preclinical and prodromal phases with pathological features including an accumulation of amyloid-beta (Aβ) peptides into extracellular Aβ plaques in the brain parenchyma and the formation of intracellular neurofibrillary tangles (NFTs) within neurons as a result of abnormal phosphorylation of microtubule-associated tau proteins. In addition, prominent activation of innate immune cells is also observed and/or followed by marked neuroinflammation...
2018: Frontiers in Neurology
Yilang Tang, Sonja Reissig, Elke Glasmacher, Tommy Regen, Florian Wanke, Alexei Nikolaev, Katharina Gerlach, Vanessa Popp, Khalad Karram, Massimo C Fantini, Jörn M Schattenberg, Peter R Galle, Markus F Neurath, Benno Weigmann, Florian C Kurschus, Nadine Hövelmeyer, Ari Waisman
BACKGROUND & AIMS: The CYLD lysine 63 deubiquitinase gene (CYLD) encodes tumor suppressor protein that is mutated in familial cylindromatosis, and variants have been associated with Crohn's disease (CD). Splice forms of CYLD that lack exons 7 and 8 regulate transcription factors and functions of immune cells. We examined expression of splice forms of CYLD in colon tissues from patients with CD and their effects in mice. METHODS: We performed immunohistochemical analyses of colon tissues from untreated patients with CD and patients without inflammatory bowel diseases (controls)...
October 10, 2018: Gastroenterology
Aliyah M Weinstein, Nicolas A Giraldo, Florent Petitprez, Catherine Julie, Laetitia Lacroix, Frédérique Peschaud, Jean-François Emile, Laetitia Marisa, Wolf H Fridman, Walter J Storkus, Catherine Sautès-Fridman
IL-1 family cytokines play a dual role in the gut, with different family members contributing either protective or pathogenic effects. IL-36γ is an IL-1 family cytokine involved in polarizing type-1 immune responses. However, its function in the gut, including in colorectal cancer pathogenesis, is not well appreciated. In a murine model of colon carcinoma, IL-36γ controls tertiary lymphoid structure formation and promotes a type-1 immune response concurrently with a decrease in expression of immune checkpoint molecules in the tumor microenvironment...
October 12, 2018: Cancer Immunology, Immunotherapy: CII
Laura M Snell, Bethany L MacLeod, Jaclyn C Law, Ivan Osokine, Heidi J Elsaesser, Kebria Hezaveh, Russell J Dickson, Marc A Gavin, Cynthia J Guidos, Tracy L McGaha, David G Brooks
CD8+ T cell exhaustion impedes control of chronic viral infection; yet how new T cell responses are mounted during chronic infection is unclear. Unlike T cells primed at the onset of infection that rapidly differentiate into effectors and exhaust, we demonstrate that virus-specific CD8+ T cells primed after establishment of chronic LCMV infection preferentially generate memory-like transcription factor TCF1+ cells that were transcriptionally and proteomically distinct, less exhausted, and more responsive to immunotherapy...
October 1, 2018: Immunity
Liliana G Ciobanu, Perminder S Sachdev, Julian N Trollor, Simone Reppermund, Anbupalam Thalamuthu, Karen A Mather, Sarah Cohen-Woods, David Stacey, Catherine Toben, K Oliver Schubert, Bernhard T Baune
The molecular factors involved in the pathophysiology of major depressive disorder (MDD) remain poorly understood. One approach to examine the molecular basis of MDD is co-expression network analysis, which facilitates the examination of complex interactions between expression levels of individual genes and how they influence biological pathways affected in MDD. Here, we applied an unsupervised gene-network based approach to a prospective experimental design using microarray genome-wide gene expression from the peripheral whole blood of older adults...
October 1, 2018: Journal of Psychiatric Research
Raquel Barajas-Azpeleta, Jianping Wu, Jason Gill, Ryan Welte, Chris Seidel, Sean McKinney, Stephane Dissel, Kausik Si
Antimicrobial peptides act as a host defense mechanism and regulate the commensal microbiome. To obtain a comprehensive view of genes contributing to long-term memory we performed mRNA sequencing from single Drosophila heads following behavioral training that produces long-lasting memory. Surprisingly, we found that Diptericin B, an immune peptide with antimicrobial activity, is upregulated following behavioral training. Deletion and knock down experiments revealed that Diptericin B and another immune peptide, Gram-Negative Bacteria Binding Protein like 3, regulate long-term but not short-term memory or instinctive behavior in Drosophila...
October 12, 2018: PLoS Genetics
Tala Shahin, Dominik Aschenbrenner, Deniz Cagdas, Sevgi Köstel Bal, Cecilia Domínguez Conde, Wojciech Garncarz, David Medgyesi, Tobias Schwerd, Betül Karaatmaca, Pınar Gur Cetinkaya, Saliha Esenboga, Stephen R F Twigg, Andrew Cant, Andrew O M Wilkie, Ilhan Tezcan, Holm H Uhlig, Kaan Boztug
Hyper-IgE Syndromes comprise a group of inborn errors of immunity. STAT3-deficient hyper-IgE syndrome is characterized by elevated serum IgE levels, recurrent infections and eczema, and characteristic skeletal anomalies. A loss-of-function biallelic mutation in IL6ST encoding the GP130 receptor subunit (p.N404Y) has very recently been identified in a singleton patient (herein referred to as PN404Y) as a novel etiology of hyper-IgE syndrome. Here, we studied a patient with hyper-IgE syndrome caused by a novel homozygous mutation in IL6ST (p...
October 11, 2018: Haematologica
Alissa K Rutman, Sarita Negi, Marco Gasparrini, Craig P Hasilo, Jean Tchervenkov, Steven Paraskevas
The autoimmune response which characterizes Type 1 diabetes (T1D) has no clear cause. Extracellular vesicles (EV) play an important role in triggering the immune response in other contexts. Here, we propose a model by which EV isolated from human islets stimulate proinflammatory immune responses and lead to peripheral blood mononuclear cell (PBMC) activation. We show that human islet EV are internalized by monocytes and B cells and lead to an increase in T-helper 1, 2 and 17 cytokine expression, as well as T and B cell proliferation...
October 10, 2018: Endocrinology
Amelia N Chang, Zhuoyi Liang, Hai-Qiang Dai, Aimee M Chapdelaine-Williams, Nick Andrews, Roderick T Bronson, Bjoern Schwer, Frederick W Alt
Genetically modified mice are commonly generated by the microinjection of pluripotent embryonic stem (ES) cells into wild-type host blastocysts1 , producing chimeric progeny that require breeding for germline transmission and homozygosity of modified alleles. As an alternative approach and to facilitate studies of the immune system, we previously developed RAG2-deficient blastocyst complementation2 . Because RAG2-deficient mice cannot undergo V(D)J recombination, they do not develop B or T lineage cells beyond the progenitor stage2 : injecting RAG2-sufficient donor ES cells into RAG2-deficient blastocysts generates somatic chimaeras in which all mature lymphocytes derive from donor ES cells...
October 10, 2018: Nature
Timothy N Hoang, Justin L Harper, Maria C Pino, Hong Wang, Luca Micci, Colin T King, Colleen S McGary, Julia B McBrien, Barbara Cervasi, Guido Silvestri, Mirko Paiardini
The bone marrow (BM) is the key anatomic site for hematopoiesis and plays a significant role in the homeostasis of mature T cells. However, very little is known on the phenotype of BM-derived CD4+ T cells, their fate during SIV infection, and their contribution to viral persistence during antiretroviral therapy (ART). Here, we characterized the immunologic and virologic status of BM-derived CD4+ T cells in rhesus macaques prior to SIV infection, during the early chronic phase of infection, and after ART. We found that BM memory CD4+ T cells are significantly depleted following SIV infection, at levels that are similar to those measured in PB...
October 10, 2018: Journal of Virology
Chrissy M Leopold Wager, Camaron R Hole, Althea Campuzano, Natalia Castro-Lopez, Hong Cai, Marley C Caballero Van Dyke, Karen L Wozniak, Yufeng Wang, Floyd L Wormley
Development of vaccines against opportunistic infections is difficult as patients most at risk of developing disease are deficient in aspects of the adaptive immune system. Here, we utilized an experimental immunization strategy to induce innate memory in macrophages in vivo. Unlike current trained immunity models, we present an innate memory-like phenotype in macrophages that is maintained for at least 70 days post-immunization and results in complete protection against secondary challenge in the absence of adaptive immune cells...
October 10, 2018: PLoS Pathogens
Elizabeth N da Silva, Alan Baker, Jalila Alshekaili, Krishna Karpe, Matthew C Cook
BACKGROUND: Chronic kidney disease (CKD) is associated with an increased risk of hepatitis B infection and impaired seroconversion to hepatitis B vaccine (HBV). Studies examining augmented vaccine schedules to enhance seroconversion have so far been inconclusive. Furthermore, the defects responsible for impaired vaccine immunity in CKD have not yet been identified. METHODS: We studied serological and cellular responses to HBV in CKD to identify a defect in vaccine-induced cellular responses that could account for impaired seroconversion in CKD and clarify the effects of an augmented vaccine dose schedule...
2018: PloS One
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