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Seminars in Immunology

Gianluca Storci, Sabrina De Carolis, Fabiola Olivieri, Massimiliano Bonafè
Inflamm-aging depicts the progressive activation of the innate immune system that accompanies human aging. Its role as a disease-predisposing condition has been proposed, but its molecular basis is still poorly understood. A wealth of literature conveys that, particularly upon stress, nuclear and mitochondrial genomes are released into the cytoplasmic and extracellular compartments. Cytoplasmic (cy) and cell-free (cf) DNA pools trigger inflammation and innate immunity at local and systemic level. In particular, cyDNA plays a crucial role in the phenomenon of cell senescence and in the cognate pro-inflammatory secretome...
September 15, 2018: Seminars in Immunology
Matthew B B McCall, Peter G Kremsner, Benjamin Mordmüller
The availability of an effective and appropriately implemented malaria vaccine would form a crucial cornerstone of public health efforts to fight this disease. Despite many decades of research, however, no malaria vaccine has yet shown satisfactory protective efficacy or been rolled-out. Validated immunological substitute endpoints have the potential to accelerate clinical vaccine development by reducing the required complexity, size, duration and cost of clinical trials. Besides facilitating clinical development of existing vaccine candidates, understanding immunological mechanisms of protection may drive the development of fundamentally new vaccination approaches...
September 12, 2018: Seminars in Immunology
Jenna L Dziki, George Hussey, Stephen F Badylak
The ability of the immune system to discriminate between healthy-self, abnormal-self, and non-self has been attributed mainly to alarmins signaling as "danger signals". It is now evident, however, that alarmins are much more complex and can perform specialized functions that can regulate a wide spectrum of processes ranging from propagation of disease to tissue homeostasis. As such, alarmins and their signaling mechanisms are now actively pursued as therapeutic targets. The clinical utility of alarmins requires an understanding of their specific localization...
August 28, 2018: Seminars in Immunology
Ali M Harandi
The discovery and wide spread use of vaccines have saved millions of lives in the past few decades. Vaccine adjuvants represent an integral part of the modern vaccines. Despite numerous efforts, however, only a handful of vaccine adjuvants is currently available for human use. A comprehensive understanding of the mechanisms of action of adjuvants is pivotal to harness the potential of existing and new adjuvants in mounting desirable immune responses to counter human pathogens. Decomposing the host response to vaccines and its components at systems level has recently been made possible owing to the recent advancements in Omics technology and cutting edge immunological assays powered by systems biology approaches...
August 16, 2018: Seminars in Immunology
Donata Medaglini, Francesco Santoro, Claire-Anne Siegrist
Ebola virus disease is a deadly infection which occurs in sporadic outbreaks. Several vaccine candidates have been developed. The most advanced candidate is the recombinant VSVΔG-ZEBOV-GP vaccine, in which the Vesicular Stomatitis Virus (VSV) envelope glycoprotein is replaced by the Zaire strain Ebola virus (ZEBOV) glycoprotein (GP). This vaccine demonstrated 100% protection in a ring vaccination trial performed in Guinea in 2015, was granted "Breakthrough Therapy Designation" by the FDA and PRIority Medicines (PRIME), and is currently (June 2018) used to support outbreak control in Democratic Republic of Congo...
July 21, 2018: Seminars in Immunology
January Weiner, Robert P Mohney, Stefan H E Kaufmann
Recent technological advances have provided deeper insights into the role of small molecules in biological processes. Metabolic profiling has thus entered the arena of -omics studies and rapidly proven its value both as stand-alone and as complement to other more advanced approaches, notably transcriptomics. Here we describe the potential of metabolic profiling for vaccinology embedded in the context of infection and immunity. This discussion is preceded by a description of the relevant technical and analytical tools for biological interpretation of metabolic data...
July 19, 2018: Seminars in Immunology
L C J de Bree, Valerie A C M Koeken, Leo A B Joosten, Peter Aaby, Christine Stabell Benn, Reinout van Crevel, Mihai G Netea
Besides protection against specific microorganisms, vaccines can induce heterologous or non-specific effects (NSE). Epidemiological data suggest that vaccination with live-attenuated vaccines such as Bacillus Calmette-Guérin (BCG), measles vaccine, and oral polio vaccine results in increased overall childhood survival, and several of these observations have been confirmed in randomized trials. Immunological mechanisms mediating NSE include heterologous lymphocyte effects and induction of innate immune memory (trained immunity)...
July 11, 2018: Seminars in Immunology
Annemieke Geluk
Leprosy is still a considerable health threat in pockets of several low and middle income countries worldwide where intense transmission is witnessed, and often results in irreversible disabilities and deformities due to delayed- or misdiagnosis. Early detection of leprosy represents a substantial hurdle in present-day leprosy health care. The dearth of timely diagnosis has, however, particularly severe consequences in the case of inflammatory episodes, designated leprosy reactions, which represent the major cause of leprosy-associated irreversible neuropathy...
June 24, 2018: Seminars in Immunology
Stephanus T Malherbe, Léanie Kleynhans, Gerhard Walzl
The development of an improved vaccine to stimulate an effective response against Mycobacterium tuberculosis (MTB) infection and disease will be a major breakthrough in the fight against TB. A lack of tools to adequately track the progression or resolution of events in TB pathogenesis that occur at bacterial loads below the threshold for culture in human samples seriously hampers vaccine development and evaluation. In this review we discuss recent studies that use new imaging applications, modalities and analysis techniques to provide insight into the dynamic processes of MTB infection and disease that are challenging to monitor...
June 15, 2018: Seminars in Immunology
Galit Alter, Tom H M Ottenhoff, Simone A Joosten
Antibodies are antigen recognizing immunoglobulins with an amazingly diverse repertoire in the antigen specific domain. The diversity of the antibody response is further increased by modifications such as somatic recombination and hypermutation. Furthermore, variation in the isotype and post-translational modifications such as Fc glycosylation further increase diversity of the effector functions. In particular variations in the glycan structures contribute significantly to the functional capacities of the antibodies...
June 11, 2018: Seminars in Immunology
Claudia Kemper, Jörg Köhl
No abstract text is available yet for this article.
June 2018: Seminars in Immunology
Christian D Sadik, Yoshishige Miyabe, Tanya Sezin, Andrew D Luster
The deposition of IgG autoantibodies in peripheral tissues and the subsequent activation of the complement system, which leads to the accumulation of the anaphylatoxin C5a in these tissues, is a common hallmark of diverse autoimmune diseases, including rheumatoid arthritis (RA) and pemphigoid diseases (PDs). C5a is a potent chemoattractant for granulocytes and mice deficient in its precursor C5 or its receptor C5aR1 are resistant to granulocyte recruitment and, consequently, to tissue inflammation in several models of autoimmune diseases...
June 2018: Seminars in Immunology
Menno van Lookeren Campagne, Admar Verschoor
Rapid elimination of microbes from the bloodstream, along with the ability to mount an adaptive immune response, are essential for optimal host-defense. Kupffer cells are strategically positioned in the liver sinusoids and efficiently capture circulating microbes from the hepatic artery and portal vein, thus preventing bacterial dissemination. In vivo and in vitro studies have probed how complement receptor of the immunoglobulin superfamily (CRIg), also referred to as Z39Ig and V-set and Ig domain-containing 4 (VSIG4), acts as a critical player in pathogen recognition and clearance...
June 2018: Seminars in Immunology
Owen A Hawksworth, Liam G Coulthard, Susanna Mantovani, Trent M Woodruff
From its discovery in the late nineteenth century, as a 'complement' to the cellular immune response, the complement system has been widely affirmed as a powerful controller of innate and adaptive immune responses. In recent decades however, new roles for complement have been discovered, with multiple complement proteins now known to function in a broad array of non-immune systems. This includes during development, where complement exerts control over stem cell populations from fertilization and implantation throughout embryogenesis and beyond post-natal development...
June 2018: Seminars in Immunology
Christian Sina, Claudia Kemper, Stefanie Derer
The complement system is part of innate sensor and effector systems such as the Toll-like receptors (TLRs). It recognizes and quickly systemically and/or locally respond to microbial-associated molecular patterns (MAMPs) with a tailored defense reaction. MAMP recognition by intestinal epithelial cells (IECs) and appropriate immune responses are of major importance for the maintenance of intestinal barrier function. Enterocytes highly express various complement components that are suggested to be pivotal for proper IEC function...
June 2018: Seminars in Immunology
Manoj K Pandey, Gregory A Grabowski, Jörg Köhl
The complement system is well appreciated for its role as an important effector of innate immunity that is activated by the classical, lectin or alternative pathway. C5a is one important mediator of the system that is generated in response to canonical and non-canonical C5 cleavage by circulating or cell-derived proteases. In addition to its function as a chemoattractant for neutrophils and other myeloid effectors, C5a and its sister molecule C3a have concerted roles in cell homeostasis and surveillance. Through activation of their cognate G protein coupled receptors, C3a and C5a regulate multiple intracellular pathways within the mitochondria and the lysosomal compartments that harbor multiple enzymes critical for protein, carbohydrate and lipid metabolism...
June 2018: Seminars in Immunology
R Halbgebauer, C Q Schmidt, C M Karsten, A Ignatius, M Huber-Lang
During local and systemic inflammation, the complement system and neutrophil granulocytes are activated not only by pathogens, but also by released endogenous danger signals. It is recognized increasingly that complement-mediated neutrophil activation plays an ambivalent role in sepsis pathophysiology. According to the current definition, the onset of organ dysfunction is a hallmark of sepsis. The preceding organ damage can be caused by excessive complement activation and neutrophil actions against the host, resulting in bystander injury of healthy tissue...
June 2018: Seminars in Immunology
Martin Kolev, Maciej M Markiewski
Complement was initially discovered as an assembly of plasma proteins "complementing" the cytolytic activity of antibodies. However, our current knowledge places this complex system of several plasma proteins, receptors, and regulators in the center of innate immunity as a bridge between the initial innate responses and adaptive immune reactions. Consequently, complement appears to be pivotal for elimination of pathogens, not only as an early response defense, but by directing the subsequent adaptive immune response...
June 2018: Seminars in Immunology
Henry Nording, Harald F Langer
The complement system is a versatile part of our immune system. Various intersection points of complement with other cells and molecules of the immune response are well described. Platelets are classically conceived as cells of hemostasis. In recent years, however, several functions of platelets "beyond thrombosis" were discovered. This review depicts the crosstalk of platelets with components of the immune system in the context of thrombo-inflammation. In particular, the various ways, in which platelets interact with the complement system, are illustrated...
June 2018: Seminars in Immunology
Yvonne Mödinger, Bettina Löffler, Markus Huber-Lang, Anita Ignatius
An integral part of innate immunity is the complement system, a defence system, consisting of fluid-phase and cell surface-bound proteins. Its role to ensure adequate responses to danger factors and thus promoting host defence against pathogens has been well described already for decades. Recently, numerous further reaching functions of complement have been discovered, among these are tissue homeostasis and regeneration, also with respect to the skeletal system. The influence of complement activation on bone was recognised first in pathological conditions of inflamed bone tissue and surrounding areas, observed, for example, in rheumatoid arthritis and osteoarthritis...
June 2018: Seminars in Immunology
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