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Translational immunology

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https://www.readbyqxmd.com/read/28443634/a-unifying-mathematical-framework-for-experimental-tcr-pmhc-kinetic-constants
#1
Jose Faro, Mario Castro, Carmen Molina-París
Receptor binding and triggering are central in Immunology as T cells activated through their T cell receptors (TCR) by protein antigens orchestrate immune responses. In order to understand receptor-ligand interactions, many groups working with different experimental techniques and assays have generated a vast body of knowledge during the last decades. However, in recent years a type of assays, referred to as two-dimensional or membrane-to-membrane, has questioned our current understanding of the role of different kinetic constants (for instance, on- versus off-rate constants) on TCR-ligand interaction and subsequent T cell activation...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28443609/the-hiv-1-viral-synapse-signals-human-foreskin-keratinocytes-to-secrete-thymic-stromal-lymphopoietin-facilitating-hiv-1-foreskin-entry
#2
Z Zhou, L Xu, A Sennepin, C Federici, Y Ganor, D Tudor, D Damotte, N Barry Delongchamps, M Zerbib, M Bomsel
The complexity of signal transduction resulting from the contact of human immunodeficiency virus type 1 (HIV-1)-infected cells and mucosal cells has hampered our comprehension of HIV-1 mucosal entry. Such process is driven efficiently only by viral synapse contacts, whereas cell-free HIV-1 remains poorly infectious. Using CD4(+) T-cells expressing only HIV-1 envelope inoculated on human adult foreskin tissues, we designed methodologies to identify the signals transduced in foreskin keratinocytes following HIV-1-envelope-dependent viral synapse formation...
April 26, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28434256/a-bioinformatics-roadmap-for-the-human-vaccines-project
#3
Richard H Scheuermann, Robert S Sinkovits, Theodore Schenkelberg, Wayne C Koff
Biomedical research has become a data intensive science in which high throughput experimentation is producing comprehensive data about biological systems at an ever-increasing pace. The Human Vaccines Project is a new public-private partnership, with the goal of accelerating development of improved vaccines and immunotherapies for global infectious diseases and cancers by decoding the human immune system. To achieve its mission, the Project is developing a Bioinformatics Hub as an open-source, multidisciplinary effort with the overarching goal of providing an enabling infrastructure to support the data processing, analysis and knowledge extraction procedures required to translate high throughput, high complexity human immunology research data into biomedical knowledge, to determine the core principles driving specific and durable protective immune responses...
April 24, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28428832/a-meta-analysis-testing-eusocial-co-option-theories-in-termite-gut-physiology-and-symbiosis
#4
Michael E Scharf, Yunpeng Cai, Yijun Sun, Ruchira Sen, Rhitoban Raychoudhury, Drion G Boucias
The termite gut accomplishes key physiologic functions that underlie termite symbiosis and sociality. However, potential candidate functions of the host-symbiont holobiome have not yet been explored across seemingly divergent processes such as digestion, immunity, caste differentiation, and xenobiotic tolerance. This study took a meta-analysis approach for concurrently studying host and symbiont gut metatranscriptome responses of the lower termite Reticulitermes flavipes, which has ancestral characteristics and hosts a diverse mix of eukaryotic and bacterial symbionts...
2017: Communicative & Integrative Biology
https://www.readbyqxmd.com/read/28422941/metabolism-related-micrornas-in-maternal-breast-milk-are-influenced-by-premature-delivery
#5
Molly C Carney, Andrij Tarasiuk, Susan L DiAngelo, Patricia Silveyra, Abigail Podany, Leann L Birch, Ian M Paul, Shannon Kelleher, Steven D Hicks
BACKGROUND: Maternal breast milk (MBM) is enriched in microRNAs, factors that regulate protein translation throughout the human body. MBM from mothers of term and preterm infants differ in nutrient, hormone, and bioactive-factor composition, but the microRNA differences between these groups have not been compared. We hypothesized that gestational age at delivery influences microRNA in MBM, particularly microRNAs involved in immunologic and metabolic regulation. METHODS: MBM from mothers of premature infants (pMBM) obtained 3-4 weeks post-delivery was compared with MBM from mothers of term infants obtained at birth (tColostrum) and 3-4 weeks post-delivery (tMBM)...
April 19, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28414183/nkg2d-a-versatile-player-in-the-immune-system
#6
REVIEW
Vedrana Jelenčić, Maja Lenartić, Felix M Wensveen, Bojan Polić
NKG2D is known as a potent activating receptor of the immune system. It is expressed on a multitude of immune cells, including NK cells and different subsets of T cells. NKG2D recognizes various MHC I-like ligands that are induced on target cells exposed to stressors such as viral infection, DNA damage and oncological transformation. NKG2D drives or facilitates cytotoxic and cytokine responses towards cells expressing its ligands to eliminate the threat. Therefore, NKG2D is usually classified as a sensor that translates cellular stress into activation signals for immune cells...
April 13, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28406322/mass-spectrometry-based-proteomic-exploration-of-the-human-immune-system-focus-on-the-inflammasome-global-protein-secretion-and-t-cells
#7
Tuula A Nyman, Martina B Lorey, Wojciech Cypryk, Sampsa Matikainen
The immune system is our defense system against microbial infections and tissue injury, and understanding how it works in detail is essential for developing drugs for different diseases. Mass spectrometry-based proteomics can provide in-depth information on the molecular mechanisms involved in immune responses. Areas covered: Summarized are the key immunology findings obtained with MS-based proteomics in the past five years, with a focus on inflammasome activation, global protein secretion, mucosal immunology, immunopeptidome and T cells...
April 24, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28401932/inflammasomes-and-intestinal-inflammation
#8
REVIEW
N Zmora, M Levy, M Pevsner-Fischer, E Elinav
The inflammasome is a cytosolic multi-protein innate immune rheostat, sensing a variety of endogenous and environmental stimuli, and regulating homeostasis or damage control. In the gastrointestinal tract, inflammasomes orchestrate immune tolerance to microbial and potentially food-related signals or drive the initiation of inflammatory responses to invading pathogens. When inadequately regulated, intestinal inflammasome activation leads to a perpetuated inflammatory response leading to immune pathology and tissue damage...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28395110/murine-models-of-transplantation-tolerance-through-mixed-chimerism-advances-and-roadblocks
#9
REVIEW
Benedikt Mahr, Thomas Wekerle
Organ transplantation is the treatment of choice for patients with end-stage organ failure but chronic immunosuppression is taking its toll in terms of morbidity and poor efficacy in preventing late graft loss. Therefore a drug-free state would be desirable where the recipient permanently accepts a donor organ while remaining otherwise fully immunologically competent. Mouse studies unveiled mixed chimerism as an effective approach to deliberately induce such donor-specific tolerance and laid the foundation for a series of clinical pilot trials...
April 10, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28393925/emil-von-behring-translational-medicine-at-the-dawn-of-immunology
#10
Stefan H E Kaufmann
On 31st March 1917, Emil von Behring passed away. Why is this event so important for immunologists a century later?
April 10, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28366940/dock8-regulates-signal-transduction-events-to-control-immunity
#11
Conor J Kearney, Katrina L Randall, Jane Oliaro
Genetic mutations in the gene encoding DOCK8 cause an autosomal recessive form of hyper immunoglobulin E syndrome (AR-HIES), referred to as DOCK8 deficiency. DOCK8 deficiency in humans results in the onset of combined immunodeficiency disease (CID), clinically associated with chronic infections with diverse microbial pathogens, and a predisposition to malignancy. It is now becoming clear that DOCK8 regulates the function of diverse immune cell sub-types, particularly lymphocytes, to drive both innate and adaptive immune responses...
April 3, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28360422/immunometabolism-in-early-and-late-stages-of-rheumatoid-arthritis
#12
REVIEW
Cornelia M Weyand, Jörg J Goronzy
One of the fundamental traits of immune cells in rheumatoid arthritis (RA) is their ability to proliferate, a property shared with the joint-resident cells that form the synovial pannus. The building of biomass imposes high demands for energy and biosynthetic precursors, implicating metabolic control as a basic disease mechanism. During preclinical RA, when autoreactive T cells expand and immunological tolerance is broken, the main sites of disease are the secondary lymphoid tissues. Naive CD4(+) T cells from patients with RA have a distinct metabolic signature, characterized by dampened glycolysis, low ATP levels and enhanced shunting of glucose into the pentose phosphate pathway...
March 31, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28356568/negative-regulators-and-their-mechanisms-in-nlrp3-inflammasome-activation-and-signalling
#13
REVIEW
Jin Kyung Kim, Hyo Sun Jin, Hyun-Woo Suh, Eun-Kyeong Jo
Inflammasomes are cytosolic multiprotein complexes that cause the release of biologically active IL-1β. The best-characterized inflammasome is the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 or Nod-like receptor protein 3) inflammasome. The NLRP3 inflammasome forms an assembly consisting of the ASC (apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain [CARD]) adaptor protein and the effector, caspase-1 (cysteine-dependent aspartate-directed protease-1)...
March 30, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28352059/korean-version-of-the-cough-symptom-score-clinical-utility-and-validity-for-chronic-cough
#14
Jae-Woo Kwon, Ji-Yong Moon, Sae-Hoon Kim, Woo-Jung Song, Min-Hye Kim, Min-Gyu Kang, Kyung-Hwan Lim, So-Hee Lee, Sang Min Lee, Jin Young Lee, Hyouk-Soo Kwon, Kyung-Mook Kim, Sang-Heon Kim, Sang-Hoon Kim, Jae-Won Jeong, Cheol-Woo Kim, Sang-Heon Cho, Byung-Jae Lee
Background/Aims: The Cough Symptom Score (CSS) is a simple, useful tool for measuring cough severity. However, there is no standard Korean version of the CSS. We developed a Korean version of the CSS and evaluated its clinical utility and validity for assessing chronic cough severity. Methods: The CSS was adapted for Korean use following a forward-backward translation procedure. Patients with chronic cough enrolled from five university hospitals were graded using the CSS and a 100-mm linear visual analog scale (VAS) of cough severity at each visit...
March 31, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28351734/chronic-hepatitis-b-immunological-profile-and-current-therapeutic-vaccines-in-clinical-trials
#15
REVIEW
Yadira Lobaina, Marie-Louise Michel
More than 250million people worldwide are chronically infected with hepatitis B virus (CHB), and over half a million die each year due to CHB-associated liver complications such as cirrhosis and hepatocellular carcinoma. The translation of immunological knowledge about CHB into therapeutic strategies aiming to a sustainable hepatitis B virus (HBV) clearance has been challenging. In recent years, however, the understanding on the immune effectors required to overcome chronicity has notably increased thanks to preclinical and clinical research...
March 25, 2017: Vaccine
https://www.readbyqxmd.com/read/28348039/what-is-the-predictive-value-of-animal-models-for-vaccine-efficacy-in-humans-reevaluating-the-potential-of-mouse-models-for-the-human-immune-system
#16
Stephen C Jameson, David Masopust
Much of what we understand about immunology, including the response to vaccines, come from studies in mice because they provide many practical advantages compared with research in higher mammals and humans. Nevertheless, modalities for preventing or treating disease do not always translate from mouse to humans, which has led to increasing scrutiny of the continued merits of mouse research. Here, we summarize the pros and cons of current laboratory mouse models for immunology research and discuss whether overreliance on nonphysiological, ultra-hygienic animal husbandry approaches has limited the ultimate translation potential of mouse-derived data to humans...
March 27, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28345177/pharmacogenomics-of-off-target-adrs
#17
REVIEW
Sarah L Garon, Rebecca K Pavlos, Katie D White, Nancy J Brown, Cosby A Stone, Elizabeth J Phillips
Off-target adverse drug reactions (ADRs) are associated with significant morbidity and costs to the healthcare system and their occurrence is not predictable based on the known pharmacological action of the drug's therapeutic effect. Off-target ADRs may or may not be associated with immunological memory although they can manifest with a variety of shared clinical features including maculopapular exanthema, severe cutaneous adverse reactions (SCARs), angioedema, pruritus, and bronchospasm. Discovery of specific genes associated with a particular ADR phenotype is a foundational component of clinical translation into screening programs for their prevention...
March 26, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28337522/pre-symptomatic-autoimmunity-in-rheumatoid-arthritis-when-does-the-disease-start
#18
REVIEW
Alexander Tracy, Christopher D Buckley, Karim Raza
It is well recognised that a state of autoimmunity, in which immunological tolerance is broken, precedes the development of symptoms in the majority of patients with rheumatoid arthritis (RA). For individuals who will later develop seropositive disease, this manifests as autoantibodies directed against proteins that have undergone specific post-translational modifications. There is evidence that the induction of this autoantibody response occurs at peripheral extra-articular mucosal sites, such as the periodontium and lung...
March 23, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28325629/towards-integrating-extracellular-matrix-and-immunological-pathways
#19
David F Boyd, Paul G Thomas
The extracellular matrix (ECM) is a complex and dynamic structure made up of an estimated 300 different proteins. The ECM is also a rich source of cytokines and growth factors in addition to numerous bioactive ECM degradation products that influence cell migration, proliferation, and differentiation. The ECM is constantly being remodeled during homeostasis and in a wide range of pathological contexts. Changes in the ECM modulate immune responses, which in turn regulate repair and regeneration of tissues. Here, we review the many components of the ECM, enzymes involved in ECM remodeling, and the signals that feed into immunological pathways in the context of a dynamic ECM...
March 18, 2017: Cytokine
https://www.readbyqxmd.com/read/28321810/overview-of-basic-immunology-for-clinical-investigators
#20
Bettzy Stephen, Joud Hajjar
Tumor exists as a complex network of structures with an ability to evolve and evade the host immune surveillance mechanism. The immune milieu which includes macrophages, dendritic cells, natural killer cells, neutrophils, mast cells, B cells, and T cells are found in the core, the invasive margin, or the adjacent stromal or lymphoid component of the tumor. The immune infiltrate is heterogeneous and varies within a patient and between patients of the same tumor histology. The location, density, functionality, and the cross talk between the immune cells in the tumor microenvironment influence the nature of immune response, prognosis, and treatment outcomes in cancer patients...
2017: Advances in Experimental Medicine and Biology
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