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Seminars in Immunology

Barbara Bottazzi, Elio Riboli, Alberto Mantovani
Aging is a key aspect of neoplasia at the level of cells, individuals and populations. Unrestrained expression and production of inflammatory mediators is a key feature of aging at the cellular and organism level. Inflammatory cells and mediators are a key component of the tumor microenvironment and drive tumor progression. Non-resolving smoldering inflammation increases the risk of cancer (the extrinsic pathway connecting inflammation and cancer). In the intrinsic pathway, genetic events that cause neoplasia (oncogenes and oncosupressor genes) orchestrate the construction of cancer-related inflammation...
November 5, 2018: Seminars in Immunology
Gabriel Kristian Pedersen, Peter Andersen, Dennis Christensen
The development of the CAF family adjuvant was initiated around 20 years ago when Statens Serum Institut was preparing its first generation protein based recombinant subunit vaccine against tuberculosis for clinical testing, but realized that there were no clinically relevant adjuvants available that would support the strong CMI response needed. Since then the aim for the adjuvant research at Statens Serum Institut has been to provide adjuvants with distinct immunogenicity profiles correlating with protection for any given infectious disease...
November 2, 2018: Seminars in Immunology
Christine Nardini, Jean-Francois Moreau, Noémie Gensous, Francesco Ravaioli, Paolo Garagnani, Maria Giulia Bacalini
A growing amount of evidences indicates that inflammaging - the chronic, low grade inflammation state characteristic of the elderly - is the result of genetic as well as environmental or stochastic factors. Some of these, such as the accumulation of senescent cells that are persistent during aging or accompany its progression, seem to be sufficient to initiate the aging process and to fuel it. Others, like exposure to environmental compounds or infections, are temporary and resolve within a (relatively) short time...
November 2, 2018: Seminars in Immunology
Claudio Franceschi, Alexey Zaikin, Susanna Gordleeva, Mikhail Ivanchenko, Francesca Bonifazi, Gianluca Storci, Massimiliano Bonafè
No abstract text is available yet for this article.
November 1, 2018: Seminars in Immunology
Steven G Reed, Darrick Carter, Corey Casper, Malcolm S Duthie, Christopher B Fox
Lipopolysaccharide (LPS) is a well-defined agonist of Toll-like receptor (TLR) 4 that activates innate immune responses and influences the development of the adaptive response during infection with Gram-negative bacteria. Many years ago, Dr. Edgar Ribi separated the adjuvant activity of LPS from its toxic effects, an effort that led to the development of monophosphoryl lipid A (MPL). MPL, derived from Salmonella minnesota R595, has progressed through clinical development and is now used in various product-enabling formulations to support the generation of antigen-specific responses in several commercial and preclinical vaccines...
October 23, 2018: Seminars in Immunology
Elena Monica Borroni, Benedetta Savino, Raffaella Bonecchi, Massimo Locati
As main drivers of leukocyte recruitment during inflammatory reactions, chemokines act as mediatrs of alarmins in priming host defense responses after tissue exposure to toxic or infectious agents, immunomediated damage, and in inflammation-driven tumors. Chemokines can therefore be considered alarm signals generated by tissues in a broad number of conditions, and mechanisms controlling chemokines biological activities are therefore key to regulate tissue reactions induced by alarmins. By transporting, presenting or scavenging different sets of chemokines, atypical chemokine receptors represent an emerign subfamily of chemokine receptors which operates in tissues as chemokine gatekeepers in order to establish and shape their gradients and coordinate leukocyte recruitment...
October 15, 2018: Seminars in Immunology
Tom H M Ottenhoff
No abstract text is available yet for this article.
October 11, 2018: Seminars in Immunology
Helen A Fletcher
Tuberculosis (TB) is the leading cause of death due to a single infectious disease and an effective vaccine would substantially accelerate global efforts to control TB. An immune correlate of protection (CoP) from TB disease could aid vaccine optimization and licensure. This paper summarises opportunities for identifying CoP and highlights results from correlates of risk studies. Although we don't have CoP, there are ongoing efficacy trials with both disease and infection endpoints which provide opportunities for such an analysis...
October 10, 2018: Seminars in Immunology
Ross Doyle, Denise M Sadlier, Catherine Godson
Inflammation is an essential response to injury and its timely and adequate resolution permits tissue repair and avoidance of chronic inflammation. Ageing is associated with increased inflammation, sub-optimal resolution and these act as drivers for a number of ageing-associated pathologies. We describe the role played by specialised proresolving lipid mediators (SPMs) in the resolution of inflammation and how insufficient levels of these mediators, or compromised responsiveness may play a role in the pathogenesis of many ageing-associated pathologies, e...
October 4, 2018: Seminars in Immunology
Tamas Fulop, Jacek M Witkowski, Fabiola Olivieri, Anis Larbi
Aging is characterized by a morpho-functional adaptation, variably affecting major physiological systems, depending on a complex interaction between genetic, environmental and stochastic factors. This dynamic interaction drives an age-related remodelling of a number of pathways/systems, providing the chance to reach the extreme limit of human life in healthy state which is reflected in the ever-increasing number of centenarians. This conceptualization implies that aging process per se and the development of the most common age-related diseases (ARD) are somewhat separate but must share somehow common set of basic biological mechanisms...
October 1, 2018: Seminars in Immunology
Eicke Latz, Peter Duewell
The process of aging is associated with the appearance of low-grade subclinical inflammation, termed inflammaging, that can accelerate age-related diseases. In Western societies the age-related inflammatory response can additionally be aggravated by an inflammatory response related to modern lifestyles and excess calorie consumption, a pathophysiologic inflammatory response that was coined metaflammation. Here, we summarize the current knowledge of mechanisms that drive both of these processes and focus our discussion the emerging concept that a key innate immune pathway, the NLRP3 inflammasome, is centrally involved in the recognition of triggers that appear during physiological aging and during metabolic stress...
September 26, 2018: 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
Mariateresa Coppola, Tom Hm Ottenhoff
Every day approximately six thousand people die of Tuberculosis (TB). Its causative agent, Mycobacterium tuberculosis (Mtb), is an ancient pathogen that through its evolution developed complex mechanisms to evade immune surveillance and acquire the ability to establish persistent infection in its hosts. Currently, it is estimated that one-fourth of the human population is latently infected with Mtb and among those infected 3-10% are at risk of developing active TB disease during their lifetime. The currently available diagnostics are not able to detect this risk group for prophylactic treatment to prevent transmission...
July 7, 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
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