Immune System
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2021 ◽  
Heinz-Josef Schmitt ◽  
Nathalie Garçon

Humans have defense mechanisms against micro-organisms exemplified by the immune system that consists of an unspecific (“innate immunity”) and specific (“adaptive immunity”) arm, leading to an effective response via humoral and cellular mechanisms. Innate immunity is activable at any time (skin, tears, ciliae, …). It includes recognition of various chemical patterns on microorganisms. Such chemical structures are detected by macrophages or dendritic cells, which travel to the draining lymph nodes and are presented to cells of the adaptive immune system. The adaptive immune system is highly specific against individual microorganisms and directed against non-self-structures. It needs days to weeks to be effective and it induces immune memory, allowing for an immediate defense response upon re-infection. As a result of presentation of non-self-structures to the adaptive immune system, highly specific antibodies and cells are generated which may kill/neutralize microbial invaders. Currently, antibody responses are the cornerstone to vaccine licensure. Functional antibody tests detecting killing/neutralizing ability are the cornerstone of vaccine-induced immunity. Tests for cell-mediated immunity are also considered. Antibody responses to vaccines can be evaluated as o Geometric Mean Titer (GMT) or Geometric Mean Concentration (GMC) o Fold-rise pre/post vaccination o Percentage of study subjects achieving a clinically relevant amount of antibody (“sero-responders”) o Reverse Cumulative Distributions (RCDs), ideally showing data pre- and post-vaccination.

2021 ◽  
Werner Solbach

Microorganisms constitute 70 percent of the biomass on Planet Earth. Comparatively few species are adapted to colonize human surfaces and form a complex Meta-Organism with manyfold mutual benefits. Occasionally, microorganisms may overcome the barriers of the skin and mucosal surfaces and may multiply locally or in multiple sites inside the body. This process is called infection. Infections can be caused by bacteria, viruses, parasites, helminths, and fungi. Immediately after infection, numerous defense mechanisms of the immune system are activated to combat replication of the microbes. There is a balance between microorganism and human defense mechanisms, which may lead to either asymptomatic infection or result in a wide spectrum of symptoms from mild to severe disease and even death. The most important factors in the diagnosis of infectious diseases are a careful history, physical examination and the appropriate collection of body fluids and tissues. Laboratory diagnosis requires between 2 and 72 hours. Wherever possible, antibiotics should only be used when sufficient evidence of efficacy is available. Then, however, they should be used as early as possible and in high doses. In addition to everyday hygiene measures, vaccination is the most effective measure to prevent infectious diseases.

2021 ◽  
Vol 12 ◽  
Elisa Jentho ◽  
Sebastian Weis

The ability to remember a previous encounter with pathogens was long thought to be a key feature of the adaptive immune system enabling the host to mount a faster, more specific and more effective immune response upon the reencounter, reducing the severity of infectious diseases. Over the last 15 years, an increasing amount of evidence has accumulated showing that the innate immune system also has features of a memory. In contrast to the memory of adaptive immunity, innate immune memory is mediated by restructuration of the active chromatin landscape and imprinted by persisting adaptations of myelopoiesis. While originally described to occur in response to pathogen-associated molecular patterns, recent data indicate that host-derived damage-associated molecular patterns, i.e. alarmins, can also induce an innate immune memory. Potentially this is mediated by the same pattern recognition receptors and downstream signaling transduction pathways responsible for pathogen-associated innate immune training. Here, we summarize the available experimental data underlying innate immune memory in response to damage-associated molecular patterns. Further, we expound that trained immunity is a general component of innate immunity and outline several open questions for the rising field of pathogen-independent trained immunity.

2021 ◽  
Vol 22 (21) ◽  
pp. 11365
Jelena Popov ◽  
Valentina Caputi ◽  
Nandini Nandeesha ◽  
David Avelar Rodriguez ◽  
Nikhil Pai

Ulcerative colitis (UC) is a chronic autoimmune disorder affecting the colonic mucosa. UC is a subtype of inflammatory bowel disease along with Crohn’s disease and presents with varying extraintestinal manifestations. No single etiology for UC has been found, but a combination of genetic and environmental factors is suspected. Research has focused on the role of intestinal dysbiosis in the pathogenesis of UC, including the effects of dysbiosis on the integrity of the colonic mucosal barrier, priming and regulation of the host immune system, chronic inflammation, and progression to tumorigenesis. Characterization of key microbial taxa and their implications in the pathogenesis of UC and colitis-associated cancer (CAC) may present opportunities for modulating intestinal inflammation through microbial-targeted therapies. In this review, we discuss the microbiota-immune crosstalk in UC and CAC, as well as the evolution of microbiota-based therapies.

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1755
Jacob McCright ◽  
Ann Ramirez ◽  
Mayowa Amosu ◽  
Arnav Sinha ◽  
Amanda Bogseth ◽  

The gastrointestinal (GI) tract is one the biggest mucosal surface in the body and one of the primary targets for the delivery of therapeutics, including immunotherapies. GI diseases, including, e.g., inflammatory bowel disease and intestinal infections such as cholera, pose a significant public health burden and are on the rise. Many of these diseases involve inflammatory processes that can be targeted by immune modulatory therapeutics. However, nonspecific targeting of inflammation systemically can lead to significant side effects. This can be avoided by locally targeting therapeutics to the GI tract and its mucosal immune system. In this review, we discuss nanomaterial-based strategies targeting the GI mucosal immune system, including gut-associated lymphoid tissues, tissue resident immune cells, as well as GI lymph nodes, to modulate GI inflammation and disease outcomes, as well as take advantage of some of the primary mechanisms of GI immunity such as oral tolerance.

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6367
Luis H. Gutiérrez-González ◽  
Selma Rivas-Fuentes ◽  
Silvia Guzmán-Beltrán ◽  
Angélica Flores-Flores ◽  
Jorge Rosas-García ◽  

PDZ (postsynaptic density (PSD95), discs large (Dlg), and zonula occludens (ZO-1)-dependent interactions are widely distributed within different cell types and regulate a variety of cellular processes. To date, some of these interactions have been identified as targets of small molecules or peptides, mainly related to central nervous system disorders and cancer. Recently, the knowledge of PDZ proteins and their interactions has been extended to various cell types of the immune system, suggesting that their targeting by viral pathogens may constitute an immune evasion mechanism that favors viral replication and dissemination. Thus, the pharmacological modulation of these interactions, either with small molecules or peptides, could help in the control of some immune-related diseases. Deeper structural and functional knowledge of this kind of protein–protein interactions, especially in immune cells, will uncover novel pharmacological targets for a diversity of clinical conditions.

2021 ◽  
Vol 8 ◽  
Geonildo Rodrigo Disner ◽  
Monica Lopes-Ferreira ◽  
Carla Lima

The aryl hydrocarbon receptor (AhR) is an environmentally responsive ligand-activated transcription factor, identified in the ‘70s for its toxic responses to halogenated polycyclic aromatic hydrocarbons, such as dioxin. Recently, AhR has been recognized as engaged in multiple physiological processes in health and diseases, particularly in the immune system, inflammatory response, tumorigenesis, and cellular differentiation by epigenetic mechanisms involving miRNAs. However, there is still scarce information about AhR-dependent miRNA regulation and miRNA-mediated epigenetic control in pathologies and therapies. In this review, we explore the mutual regulation of AhR and miRNA over the last decade of studies since many miRNAs have dioxin response elements (DRE) in their 3’ UTR, as well as AhR might contain binding sites of miRNAs. TCDD is the most used ligand to investigate the impact of AhR activation, and the immune system is one of the most sensitive of its targets. An association between TCDD-activated AhR and epigenetic mechanisms like post-transcriptional regulation by miRNAs, DNA methylation, or histone modification has already been confirmed. Besides, several studies have shown that AhR-induced miR-212/132 cluster suppresses cancers, attenuates autoimmune diseases, and has an anti-inflammatory role in different immune responses by regulating cytokine levels and immune cells. Together the ever-expanding new AhR roles and the miRNA therapeutics are a prominent segment among biopharmaceuticals. Additionally, AhR-activated miRNAs can serve as valuable biomarkers of diseases, notably cancer progression or suppression and chemical exposure. Once AhR-dependent gene expression may hinge on the ligand, cell type, and context singularity, the reviewed outcomes might help contextualize state of the art and support new trends and emerging opportunities in the field.

Photonics ◽  
2021 ◽  
Vol 8 (11) ◽  
pp. 462
Yuliya Maklygina ◽  
Igor Romanishkin ◽  
Aleksej Skobeltsin ◽  
Dina Farrakhova ◽  
Victor Loschenov

In this work, a new approach was tested to assess the cellular composition of tissues by time-resolved methods of fluorescence analysis of exogenous and endogenous fluorophores. First of all, the differences in fluorescence kinetics of endogenous fluorophores (coenzymes NADH and FAD) in tumour and immunocompetent cells were determined. After that, differences in fluorescence kinetics of photosensitizer 5 ALA-induced protoporphyrin IX were established due to its different metabolism in cells of different phenotypes. Kinetics of photoluminescence of NADH and FAD coenzymes as well as photosensitizer were studied by means of two different methods: time-resolved spectroscopy based on a streak-camera and fibre optic neuroscopy, which served to perform process monitoring and regular fluorescence diagnosis of the probed region. Time-resolved fluorescence microscopy (FLIM) was used as a control technique. Time-resolved spectroscopic fluorescence lifetime analysis was performed on sexually mature female rats induced with glioma C6 brain tumour under in vivo conditions; thus, under conditions where the immune system actively intervenes in the process of oncogenesis. In this regard, the aim of the study was to recognize the cellular composition of the brain tumour tissue, namely the ratio of cancer and immunocompetent cells and their mutual localization. Understanding the role of the immune system thus provides new ways and approaches for further diagnosis and therapy, making tumour-associated immune cells a prime target for modern therapies.

2021 ◽  
pp. 2100041
Patricia Sosa‐Acosta ◽  
Rafael D. Melani ◽  
Mauricio Quiñones‐Vega ◽  
Adriana Melo ◽  
Patrícia P. Garcez ◽  

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