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"Immunity"
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Trained immunity, tolerance, priming and differentiation: distinct immunological processes
The similarities and differences between trained immunity and other immune processes are the subject of intense interrogation. Therefore, a consensus on the definition of trained immunity in both in vitro and in vivo settings, as well as in experimental models and human subjects, is necessary for advancing this field of research. Here we aim to establish a common framework that describes the experimental standards for defining trained immunity.
Journal Article
Chloroplast immunity illuminated
The chloroplast has recently emerged as pivotal to co-ordinating plant defence responses and as a target of plant pathogens. Beyond its central position in oxygenic photosynthesis and primary metabolism – key targets in the complex virulence strategies of diverse pathogens – the chloroplast integrates, decodes and responds to environmental signals. The capacity of chloroplasts to synthesize phytohormones and a diverse range of secondary metabolites, combined with retrograde and reactive oxygen signalling, provides exquisite flexibility to both perceive and respond to biotic stresses. These processes also represent a plethora of opportunities for pathogens to evolve strategies to directly or indirectly target ‘chloroplast immunity’. This review covers the contribution of the chloroplast to pathogen associated molecular pattern and effector triggered immunity as well as systemic acquired immunity. We address phytohormone modulation of immunity and surmise how chloroplast-derived reactive oxygen species underpin chloroplast immunity through indirect evidence inferred from genetic modification of core chloroplast components and direct pathogen targeting of the chloroplast. We assess the impact of transcriptional reprogramming of nuclear-encoded chloroplast genes during disease and defence and look at future research challenges.
Journal Article
Innate, adaptive, and cell-autonomous immunity against Toxoplasma gondii infection
Hosts have been fighting pathogens throughout the evolution of all infectious diseases.
Toxoplasma gondii
is one of the most common infectious agents in humans but causes only opportunistic infection in healthy individuals. Similar to antimicrobial immunity against other organisms, the immune response against
T. gondii
activates innate immunity and in turn induces acquired immune responses. After activation of acquired immunity, host immune cells robustly produce the proinflammatory cytokine interferon-γ (IFN-γ), which activates a set of IFN-γ-inducible proteins, including GTPases. IFN-inducible GTPases are essential for cell-autonomous immunity and are specialized for effective clearance and growth inhibition of
T. gondii
by accumulating in parasitophorous vacuole membranes. Recent studies suggest that the cell-autonomous immune response plays a protective role in host defense against not only
T. gondii
but also various intracellular bacteria. Moreover, the negative regulatory mechanisms of such strong immune responses are also important for host survival after infection. In this review, we will discuss in detail recent advances in the understanding of host defenses against
T. gondii
and the roles played by cell-autonomous immune responses.
Toxoplasmosis: Insights into immunity
Researchers are extensively studying immune responses to the single-celled parasite
Toxoplasma gondii
, which infects around one-third of humans, often harmlessly, but can cause life-threatening toxoplasmosis infections in patients with weakened immune systems. Masahiro Yamamoto and Miwa Sasai at Osaka University in Japan review recent advances in understanding the interactions between the immune system and the parasite. They consider non-specific ‘innate’ immune responses and also the ‘acquired’ responses that target specific parts of the parasite, referred to as antigens. Methods that selectively switch off genes in mice are revealing details presumed to also be relevant for humans. Significant molecules, molecular signaling pathways and immune-regulating processes are being identified. Recent studies suggest cell-autonomous immunity, the ability of host cells to defend themselves against attack, plays a significant role in fighting
Toxoplasma gondii
infection.
Journal Article
Between hope and fear : a history of vaccines and human immunity
\"An intelligent and compelling examination of the science of immunity, the public policy implications of vaccine denial, and the real-world outcomes of failing to vaccinate. If you have a child in school, you may have heard stories of long-dormant diseases suddenly reappearing--cases of measles, mumps, rubella, and whooping cough cropping up everywhere from elementary schools to Ivy League universities. How does a small group of people's failure to vaccinate have the potential to affect future generations? Are we at a turning point in medical history, where deadly diseases, once dormant, flourish anew? Will our children face summers of abandoned swimming pools due to polio outbreaks just like our great-grandparents did? Pioneering medical researcher Michael Kinch tells the remarkable story of vaccine-preventable infectious diseases in [this book], which explains how the science of immunity actually works and places immunology within the context of its social and political implications. While detailing the history of vaccine invention, from the steppes of Mongolia to the serendipitous connection between cowpox and smallpox, Kinch reveals the ominous reality that our victories against vaccine-preventable diseases are not permanent--and could easily be undone. ... Between Hope and Fear illuminates the fascinating intersection of science, technology, and disease that has helped eradicate many of the deadliest plagues known to man.\"-- Jacket.
Book
Is atherosclerosis an autoimmune disease?
Immunologic research into pathogenic mechanisms operating in autoimmune-mediated atherosclerosis initially focused on adaptive immunity. Current interest is directed to more basic inflammatory mechanisms. Chronic inflammation (innate immunity-associated) may trigger initial events that can lead to atherosclerotic cardiovascular disease. This chronic inflammation may start early in life and be perpetuated by classic atherosclerosis risk factors. Lipid peroxidation of low-density lipoprotein seems to be a key event in the initiation and progression of atherosclerosis. Oxidized low-density lipoprotein triggers inflammatory and immunogenic events that promote endothelial dysfunction and the synthesis and secretion of pro-inflammatory cytokines, leading to an autoimmune response capable of accelerating the intracellular accumulation of lipids within atherosclerotic plaques. Oxidized low-density lipoprotein binds β2-glycoprotein I to form circulating complexes found in both autoimmune and non-autoimmune atherosclerosis. It is likely that β2-glycoprotein I and/or these complexes contribute to early atherogenesis by stimulating pro-inflammatory innate immunity through endogenous sensors and inflammasome/interleukin-1 pathways. We discuss the chronic inflammatory (innate) and autoimmune (adaptive) responses operating in atherosclerosis to discern the role of autoimmunity in atherosclerotic cardiovascular disease.
Journal Article
Everland
London is a ruin, destroyed by German bombs, ravaged by the Horologia virus, and ruled by the ruthless Captain Hanz Otto Oswald Kretschmer, whose Marauders search for and seize the children who are immune to the virus in the hope that their blood will produce a cure--their latest victim is sixteen-year-old Gwen Darling's younger sister and Gwen will do anything to get her back, even join up with Pete and his gang of Lost Boys living in a city hidden underground.
Book
Personalized vaccinology: A review
At the current time, the field of vaccinology remains empirical in many respects. Vaccine development, vaccine immunogenicity, and vaccine efficacy have, for the most part, historically been driven by an empiric “isolate-inactivate-inject” paradigm. In turn, a population-level public health paradigm of “the same dose for everyone for every disease” model has been the normative thinking in regard to prevention of vaccine-preventable infectious diseases. In addition, up until recently, no vaccines had been designed specifically to overcome the immunosenescence of aging, consistent with a post-WWII mentality of developing vaccines and vaccine programs for children. It is now recognized that the current lack of knowledge concerning how immune responses to vaccines are generated is a critical barrier to understanding poor vaccine responses in the elderly and in immunoimmaturity, discovery of new correlates of vaccine immunogenicity (vaccine response biomarkers), and a directed approach to new vaccine development.
The new fields of vaccinomics and adversomics provide models that permit global profiling of the innate, humoral, and cellular immune responses integrated at a systems biology level. This has advanced the science beyond that of reductionist scientific approaches by revealing novel interactions between and within the immune system and other biological systems (beyond transcriptional level), which are critical to developing “downstream” adaptive humoral and cellular responses to infectious pathogens and vaccines. Others have applied systems level approaches to the study of antibody responses (a.k.a. “systems serology”), [1] high-dimensional cell subset immunophenotyping through CyTOF, [2,3] and vaccine induced metabolic changes [4]. In turn, this knowledge is being utilized to better understand the following: identifying who is at risk for which infections; the level of risk that exists regarding poor immunogenicity and/or serious adverse events; and the type or dose of vaccine needed to fully protect an individual. In toto, such approaches allow for a personalized approach to the practice of vaccinology, analogous to the substantial inroads that individualized medicine is playing in other fields of human health and medicine. Herein we briefly review the field of vaccinomics, adversomics, and personalized vaccinology.
Journal Article