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Bakiah Shaharuddin, Sajjad Ahmad, Nani Md Latar, Simi Ali, Annette Meeson
: : Limbal stem cell (LSC) deficiency is a visually debilitating condition caused by abnormal maintenance of LSCs. It is treated by transplantation of donor-derived limbal epithelial cells (LECs), the success of which depends on the presence and quality of LSCs within the transplant. Understanding the immunobiological responses of these cells within the transplants could improve cell engraftment and survival. However, human corneal rings used as a source of LSCs are not always readily available for research purposes...
October 14, 2016: Stem Cells Translational Medicine
Daniel H Li, James B Whitmore, Wentian Guo, Yuan Ji
Recent trials of adoptive cell therapy (ACT), such as the chimeric antigen receptor T (CAR-T) cells therapy, have demonstrated promising therapeutic effects for cancer patients. A main issue in the product development is to decide appropriate dose of ACT. Traditional phase 1 trial designs for cytotoxic agents explicitly assume that toxicity increases monotonically with dose levels and implicitly assume the same for efficacy to justify dose escalation. ACT usually induces rapid responses, and the monotonic dose-response assumption is unlikely to hold due to its immunobiological activities...
October 14, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yihua Zhou
Hepatitis E virus (HEV) causes acute self-limiting hepatitis in most cases and chronic infection in rare circumstances. It is believed to be noncytopathic, so immunologically mediated events should play important roles in its pathogenesis and infection outcomes. The anti-HEV antibody response was clarified when the major antigenic determinants on the ORF2 polypeptide were determined, which are located in its C-terminal portion. This subregion also forms the conformational neutralization epitopes. Robust anti-HEV immunoglobulin M (IgM) and IgG responses usually develop 3-4 weeks after infection in experimentally infected nonhuman primates...
2016: Advances in Experimental Medicine and Biology
Bin Xu, Lujun Chen, Jing Li, Xiao Zheng, Liangrong Shi, Changping Wu, Jingting Jiang
The detailed understanding of the immunobiology of tumor microenvironment has recently translated into new therapeutic approach against human cancers. Besides the role of immune cells mediating adaptive immune responses, the tumor infiltrating components of the innate immune system including, neutrophils, mast cells, NK cells, and macrophages, also role importantly in anti-tumor immunity. In our present study, we retrospectively analyzed the prognostic value of the densities of tumor infiltrating NK cells and macrophages in esophageal cancer tissues derived from stage II+III patients...
October 5, 2016: Oncotarget
Mei Song, Xiaojing Ma
Interleukin-35 (IL-35) is the latest addition to the IL-12 family of heterodimeric cytokines, consisting of IL-12 p35 subunit and IL-27β subunit Epstein-Barr virus induced 3 (EBI3). Since its discovery, IL-35 has been shown to exhibit immunosuppressive activities which are distinct from other members of IL-12 family. IL-35 is also unique in that it is expressed primarily by regulatory T-cells (Tregs) rather than by antigen-presenting cells (APCs). IL-35 can directly suppress effector T-cell proliferation and function and inhibit the differentiation of Th17 cells...
2016: Advances in Experimental Medicine and Biology
Shigeyuki Kawa
High serum immunoglobulin (Ig) G4 concentration and abundant IgG4-bearing plasma cell infiltration are characteristic features in autoimmune pancreatitis (AIP). AIP is also complicated with a variety of other organ involvements that commonly share marked IgG4-bearing plasma cell infiltration, suggesting the existence of a systemic disease associated with IgG4 currently recognized as IgG4-related disease (IgG4-RD). However, it is controversial whether IgG4 plays a role in the pathogenesis of AIP or IgG4-RD through such characteristic attributes as Fab-arm exchange and rheumatoid factor (RF)-like activity...
September 21, 2016: Current Topics in Microbiology and Immunology
Martin Prince Alphonse, Trang T Duong, Chisato Shumitzu, Truong Long Hoang, Brian W McCrindle, Alessandra Franco, Stéphane Schurmans, Dana J Philpott, Martin L Hibberd, Jane Burns, Taco W Kuijpers, Rae S M Yeung
Kawasaki disease (KD) is a multisystem vasculitis that predominantly targets the coronary arteries in children. Phenotypic similarities between KD and recurrent fever syndromes point to the potential role of inflammasome activation in KD. Mutations in NLRP3 are associated with recurrent fever/autoinflammatory syndromes. We show that the KD-associated genetic polymorphism in inositol-triphosphate 3-kinase C (ITPKC) (rs28493229) has important functional consequences, governing ITPKC protein levels and thereby intracellular calcium, which in turn regulates NLRP3 expression and production of IL-1β and IL-18...
September 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Keith Rubin, Steven Glazer
While a number of endogenous risk factors including age and genetics are established for Alzheimer's disease (AD), identification of acquired, potentially preventable or treatable causes, remains limited. In this paper, we review three epidemiologic case studies and present extensive biologic, immunologic and anatomic evidence to support a novel hypothesis that Bordetella pertussis (BP), the bacterium better known to cause whooping cough, is an important potential cause of AD. Cross-cultural documentation of nasopharyngeal subclinical BP colonization reflecting BP-specific mucosal immunodeficiency, proximate anatomy of intranasal mucosal surfaces to central nervous system (CNS) olfactory pathways, and mechanisms by which BP and BP toxin account for all hallmark pathology of AD are reviewed, substantiating biologic plausibility...
September 28, 2016: Immunobiology
A Richard Kitching, Joshua D Ooi
The generation of inbred mouse strains in the late 19th and early 20th centuries, coupled with the later establishment of specific pathogen-free animal research facilities created a powerful biological platform for exploration of the immune system in health and disease. Studies in this setting have been responsible for huge advances in our understanding of immunobiology and disease, including immune-mediated kidney disease. However, whereas this reductionist and relatively standardized approach allows us to make sense of complex disease biology, it takes place in controlled environments that clearly differ from those that we humans encounter in everyday life...
September 28, 2016: Kidney International
José A Melero, Vicente Mas, Jason S McLellan
Extraordinary progress in the structure and immunobiology of the human respiratory syncytial virus glycoproteins has been accomplished during the last few years. Determination of the fusion (F) glycoprotein structure folded in either the prefusion or the postfusion conformation was an inspiring breakthrough not only to understand the structural changes associated with the membrane fusion process but additionally to appreciate the antigenic intricacies of the F protein. Furthermore, these developments have opened new avenues for structure-based designs of promising hRSV vaccine candidates...
September 28, 2016: Vaccine
Isabel Ferreira, Joana Liberal, João Martins, Ana Silva, Bruno M Neves, Maria Teresa Cruz
An intricate interplay between innate and adaptive immune cells is crucial for an effective immune response during disease, infection and vaccination. This interplay is manly performed by dendritic cells (DCs), which are professional antigen presenting cells (APCs) with unparalleled capacity to translate innate to adaptive immunity. They effectively recognize and uptake antigens, migrate to lymphoid tissues, and activate naïve T-cells. To enable rapid pathogen detection DCs utilize numerous germline encoded pattern recognition receptors (PRR) that recognize conserved pathogen associated molecular patterns (PAMPs) or danger associated molecular patterns (DAMPs)...
September 21, 2016: Current Drug Targets
Vishvanath Nene, W Ivan Morrison
Despite having different cell tropism, the pathogenesis and immunobiology of the diseases caused by Theileria parva and T. annulata are remarkably similar. Live vaccines have been available for both parasites for over 40 years, but although they provide strong protection, practical disadvantages have limited their widespread application. Efforts to develop alternative vaccines using defined parasite antigens have focused on the sporozoite and intracellular schizont stages of the parasites. Experimental vaccination studies using viral vectors expressing T...
September 20, 2016: Parasite Immunology
Mario Galgani, Veronica De Rosa, Antonio La Cava, Giuseppe Matarese
Intracellular metabolism is central to cell activity and function. CD4(+)CD25(+) regulatory T cells (Tregs) that express the transcription factor FOXP3 play a pivotal role in the maintenance of immune tolerance to self. Recent studies showed that the metabolism and function of Tregs are influenced significantly by local environmental conditions and the availability of certain metabolites. It also was reported that defined metabolic programs associate with Treg differentiation, expression of FOXP3, and phenotype stabilization...
October 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Vedran Radojcic, Ivan Maillard
Solid organ and allogeneic hematopoietic cell transplantation have become standard therapeutic interventions that save patient lives and improve quality of life. Our enhanced understanding of transplantation immunobiology has refined clinical management and improved outcomes. However, organ rejection and graft-versus-host disease remain major obstacles to the broader successful application of these therapeutic procedures. Notch signaling regulates multiple aspects of adaptive and innate immunity. Preclinical studies identified Notch signaling as a promising target in autoimmune diseases, as well as after allogeneic hematopoietic cell and solid organ transplantation...
September 8, 2016: Transplantation
Laura Andrade Lagôa Nóbrega, Hillegonda Maria Dutilh Novaes, Ana Marli Christovam Sartori
OBJECTIVE: To describe the Reference Centers for Special Immunobiologicals and evaluate their implementation considering formal regulations. METHODS: We conducted a program evaluation, of evaluative research type. From August 2011 to January 2012, a questionnaire was applied to the 42 Reference Centers for Special Immunobiologicals existing in the Country, approaching the structure, human resources, and developed activities dimensions. We conducted a descriptive analysis of data and used a clustering for binary data with the squared Euclidean distance, by the farthest neighbor method, to aggregate services with similar features...
August 4, 2016: Revista de Saúde Pública
Marija Zaric, Bárbara Ibarzo Yus, Petya Petrova Kalcheva, Linda Sylvia Klavinskis
INTRODUCTION: Microneedle array platforms are a promising technology for vaccine delivery, due to their ease of administration with no sharp waste generated, small size, possibility of targeted delivery to the specified skin depth and efficacious delivery of different vaccine formulations, including viral vectors. AREAS COVERED: Attributes and challenges of the most promising viral vector candidates that have advanced to the clinic and that have been leveraged for skin delivery by microneedles; The importance of understanding the immunobiology of antigen-presenting cells in the skin, in particular dendritic cells, in order to generate further improved skin vaccination strategies; recent studies where viral vectors expressing various antigens have been coupled with microneedle technology to examine their potential for improved vaccination...
September 2, 2016: Expert Opinion on Drug Delivery
Brett P Bielory, Steven P Shah, Terrence P O'Brien, Victor L Perez, Leonard Bielory
PURPOSE OF REVIEW: The present review provides an overview on the potential of different systemic and topical treatments in chronic forms of ocular allergy and dry eye disorder (DED). The impact on anterior surface of ocular inflammatory disorder encompasses an array of conditions, which are frequently underreported. This can contribute to underdiagnoses and ineffective management from healthcare providers such as an allergist and/or ophthalmologist who routinely provide care for these common disorders...
October 2016: Current Opinion in Allergy and Clinical Immunology
Dirk P Dittmer, Blossom Damania
Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8, is the etiologic agent underlying Kaposi sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. This human gammaherpesvirus was discovered in 1994 by Drs. Yuan Chang and Patrick Moore. Today, there are over five thousand publications on KSHV and its associated malignancies. In this article, we review recent and ongoing developments in the KSHV field, including molecular mechanisms of KSHV pathogenesis, clinical aspects of KSHV-associated diseases, and current treatments for cancers associated with this virus...
September 1, 2016: Journal of Clinical Investigation
Lucy M Turner, Christian Alsterberg, Andrew D Turner, S K Girisha, Ashwin Rai, Jonathan N Havenhand, M N Venugopal, Indrani Karunasagar, Anna Godhe
There is growing evidence that climate change will increase the prevalence of toxic algae and harmful bacteria, which can accumulate in marine bivalves. However, we know little about any possible interactions between exposure to these microorganisms and the effects of climate change on bivalve health, or about how this may affect the bivalve toxin-pathogen load. In mesocosm experiments, mussels, Perna viridis, were subjected to simulated climate change (warming and/or hyposalinity) and exposed to harmful bacteria and/or toxin-producing dinoflagellates...
2016: Scientific Reports
Pavan Patel, Steven E Schutzer, Nikolaos Pyrsopoulos
Hepatocellular carcinoma is on the rise and occurs in the setting of chronic liver disease and cirrhosis. Though treatment modalities are available, mortality from this cancer remains high. Medical therapy with the utilization of biologic compounds such as the Food and Drug Administration approved sorafenib might be the only option that can increase survival. Immunotherapy, with modern pharmacologic developments, is a new frontier in cancer therapy and therefore the immunobiology of hepatocarcinogenesis is under investigation...
August 15, 2016: World Journal of Gastrointestinal Pathophysiology
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