scholarly journals The coagulation system and its function in early immune defense

2014 ◽  
Vol 112 (10) ◽  
pp. 640-648 ◽  
Author(s):  
Tom van der Poll ◽  
Heiko Herwald
Keyword(s):  
Immune System ◽  
Infectious Diseases ◽  
Blood Coagulation ◽  
Innate Immune System ◽  
Host Response ◽  
Immune Defense ◽  
Innate Immune ◽  
Coagulation System ◽  
High Morbidity ◽  
Phylogenetic Studies

SummaryBlood coagulation has a Janus-faced role in infectious diseases. When systemically activated, it can cause serious complications associated with high morbidity and mortality. However, coagulation is also part of the innate immune system and its local activation has been found to play an important role in the early host response to infection. Though the latter aspect has been less investigated, phylogenetic studies have shown that many factors involved in coagulation have ancestral origins which are often combined with anti-microbial features. This review gives a general overview about the most recent advances in this area of research also referred to as immunothrombosis.

Effect of plinabulin, a novel late-clinical stage immunotherapeutic agent on the adaptive and innate immune system.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 8-8
Author(s):  
Ramon W. Mohanlal ◽  
Lan Huang
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Clinical Stage ◽  
Onset Time ◽  
Immune Defense ◽  
Innate Immune ◽  
Dependent Manner ◽  
Breast Cancer Patients ◽  
Post Dose ◽  
The Impact

8 Background: Plinabulin (Plin) is a small molecule Dendritic Cell modulator, which in the presence of antigen, increases T-cell proliferation in an antigen-dependent manner marrow. The addition of Plin to Docetaxel (Doc) improved mOS with 4.6 months vs Docetaxel monotherapy, and prolonged DoR with more than 1 year (p < 0.05), which is indicative of an immune-mediated mechanism of action (Mohanlal, ASCO-SITC 2017). Neutrophils are our first line of innate immune defense against foreign invaders. We previously reported that Plinabulin prevents chemotherapy (Chemo) Induced Neutropenia (CIN) in patients receiving Doc or TAC throughout the cycle (Doc, Doxorubicin, Cyclophosphamide) (Blayney ASH 2018, St Gallen 2019). Here we analyzed the onset time of neutrophil increase following Plin administration. In addition, we analyzed the impact of Plin on plasma haptoglobin, which is an acute phase protein with anti-inflammatory effects together with immune-enhancing effects and is an integral part of innate immunity (Kristiansen Nature 2001). Methods: Absolute neutrophil count (ANC) and haptoglobin data were analyzed from Phase 2 study BPI-2358-106 (NCT03294577) with 10 (n = 15), 20 (n = 15) and 30 mg/m2 (n = 12) Plin in Breast Cancer patients receiving TAC. Plin was administered on Day 1. ANC and Haptoglobin were analyzed by a Central Laboratory (Covance), from blood draws at predose, and post-dose Plin at Day 2,3,6,7,8,9,10,11,12,13 and 15, and changes relative to predose value were evaluated. Results: Plin dose-dependently increased ANC within 1 day (P < 0.001) and Haptoglobin within 3 days (P < 0.03) of dosing. Mean haptoglobin (P < 0.0005) and ANC (P < 0.001) levels increased with ~two-fold vs baseline levels. ANC levels remained increased for approximately 1 week and haptoglobin levels for > 3 weeks. Conclusions: Based on Plinabulin’s ability to stimulate the innate system, together with its previously reported evidence as a potent activator of the adaptive immune system (Mohanlal, ASCO-SITC 2017), it is concluded that Plinabulin is a potent stimulator of the adaptive and innate immune system. Clinical trial information: NCT03294577.

scholarly journals Neutrophils—From Bone Marrow to First-Line Defense of the Innate Immune System

2021 ◽  
Vol 12 ◽  
Author(s):  
Richard Felix Kraus ◽  
Michael Andreas Gruber
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Current Knowledge ◽  
Immune Defense ◽  
Innate Immune ◽  
Human Organism ◽  
Polymorphonuclear Cells ◽  
Target Tissue ◽  
First Line

Neutrophils (polymorphonuclear cells; PMNs) form a first line of defense against pathogens and are therefore an important component of the innate immune response. As a result of poorly controlled activation, however, PMNs can also mediate tissue damage in numerous diseases, often by increasing tissue inflammation and injury. According to current knowledge, PMNs are not only part of the pathogenesis of infectious and autoimmune diseases but also of conditions with disturbed tissue homeostasis such as trauma and shock. Scientific advances in the past two decades have changed the role of neutrophils from that of solely immune defense cells to cells that are responsible for the general integrity of the body, even in the absence of pathogens. To better understand PMN function in the human organism, our review outlines the role of PMNs within the innate immune system. This review provides an overview of the migration of PMNs from the vascular compartment to the target tissue as well as their chemotactic processes and illuminates crucial neutrophil immune properties at the site of the lesion. The review is focused on the formation of chemotactic gradients in interaction with the extracellular matrix (ECM) and the influence of the ECM on PMN function. In addition, our review summarizes current knowledge about the phenomenon of bidirectional and reverse PMN migration, neutrophil microtubules, and the microtubule organizing center in PMN migration. As a conclusive feature, we review and discuss new findings about neutrophil behavior in cancer environment and tumor tissue.

scholarly journals Perinatal Environment Shapes Microbiota Colonization And Infant Growth: Impact On Host Response And Intestinal Function

2020 ◽  
Author(s):  
Maria Carmen Collado ◽  
Marta Selma-Royo ◽  
Marta Calatayud ◽  
Izaskun García-Mantrana ◽  
Anna Parra-Llorca ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Gut Microbiota ◽  
Intestinal Epithelium ◽  
Innate Immune System ◽  
Host Response ◽  
Innate Immune ◽  
Epithelial Barrier ◽  
Intestinal Function ◽  
Intestinal Maturation

Abstract Background: Early microbial colonization triggers processes that result in intestinal maturation and immune priming. Perinatal factors, especially those associated with birth, including both mode and place of delivery are critical to shaping the infant gut microbiota with potential health consequences. Methods: Gut microbiota profile of 180 healthy infants (n=23 born at home and n=157 born in hospital, 41.7% via caesarean section [CS]) was analyzed by 16S rRNA gene sequencing at birth, seven days and one month of life. Breastfeeding habits, infant clinical data, including length, weight and antibiotic exposure, were collected up to 18 months of life. Long-term personalized in vitro models of the intestinal epithelium and innate immune system were used to assess the link between gut microbiota composition, intestinal function and immune response. Results: Microbiota profiles were shaped by the place and mode of delivery, and they had a distinct biological impact on the immune response and intestinal function in epithelial/immune cell models. Bacteroidetes and Bifidobacterium genus were decreased in C-section infants, who showed higher z-scores BMI and W/L during the first 18 months of life. Intestinal simulated epithelium had a stronger epithelial barrier function and intestinal maturation, alongside a higher immunological response (TLR4 route activation and pro-inflammatory cytokine release), when exposed to home-birth fecal supernatants, compared with CS. Distinct host response could be associated with different microbiota profiles. Conclusions: Mode and place of birth influence the neonatal gut microbiota, likely shaping its interplay with the host through the maturation of the intestinal epithelium, regulation of the intestinal epithelial barrier and control of the innate immune system during early life, which can affect the phenotypic responses linked to metabolic processes in infants.

scholarly journals Tweaking Innate Immunity: The Promise of Innate Immunologicals as Anti-Infectives

2006 ◽  
Vol 17 (5) ◽  
pp. 307-314 ◽  
Author(s):  
Kenneth L Rosenthal
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Immune Responses ◽  
Innate Immune System ◽  
Immune Defense ◽  
Innate Immune ◽  
Parasitic Infections ◽  
Type I ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

New and exciting insights into the importance of the innate immune system are revolutionizing our understanding of immune defense against infections, pathogenesis, and the treatment and prevention of infectious diseases. The innate immune system uses multiple families of germline-encoded pattern recognition receptors (PRRs) to detect infection and trigger a variety of antimicrobial defense mechanisms. PRRs are evolutionarily highly conserved and serve to detect infection by recognizing pathogen-associated molecular patterns that are unique to microorganisms and essential for their survival. Toll-like receptors (TLRs) are transmembrane signalling receptors that activate gene expression programs that result in the production of proinflammatory cytokines and chemokines, type I interferons and antimicrobial factors. Furthermore, TLR activation facilitates and guides activation of adaptive immune responses through the activation of dendritic cells. TLRs are localized on the cell surface and in endosomal/lysosomal compartments, where they detect bacterial and viral infections. In contrast, nucleotide-binding oligomerization domain proteins and RNA helicases are located in the cell cytoplasm, where they serve as intracellular PRRs to detect cytoplasmic infections, particularly viruses. Due to their ability to enhance innate immune responses, novel strategies to use ligands, synthetic agonists or antagonists of PRRs (also known as 'innate immunologicals') can be used as stand-alone agents to provide immediate protection or treatment against bacterial, viral or parasitic infections. Furthermore, the newly appreciated importance of innate immunity in initiating and shaping adaptive immune responses is contributing to our understanding of vaccine adjuvants and promises to lead to improved next-generation vaccines.

scholarly journals The Role of Innate Immunity in Osteoarthritis: When Our First Line of Defense Goes On the Offensive

2015 ◽  
Vol 42 (3) ◽  
pp. 363-371 ◽  
Author(s):  
Eric W. Orlowsky ◽  
Virginia Byers Kraus
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Defense Mechanisms ◽  
Immune Defense ◽  
Innate Immune ◽  
Low Grade ◽  
Wear And Tear ◽  
Low Grade Inflammation

Although osteoarthritis (OA) has existed since the dawn of humanity, its pathogenesis remains poorly understood. OA is no longer considered a “wear and tear” condition but rather one driven by proteases where chronic low-grade inflammation may play a role in perpetuating proteolytic activity. While multiple factors are likely active in this process, recent evidence has implicated the innate immune system, the older or more primitive part of the body’s immune defense mechanisms. The roles of some of the components of the innate immune system have been tested in OA modelsin vivoincluding the roles of synovial macrophages and the complement system. This review is a selective overview of a large and evolving field. Insights into these mechanisms might inform our ability to identify patient subsets and give hope for the advent of novel OA therapies.

scholarly journals Increase of the innate immunity and hemostasis correction in calves using medications with immunomodulating and biostimulating activity

2020 ◽  
Vol 2020 (2) ◽  
pp. 31-38
Author(s):  
Aleksandr Sanin ◽  
Aleksandr Narovlyanskiy ◽  
Aleksandr Pronin ◽  
Tat'yana Kozhevnikova
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Infectious Diseases ◽  
Innate Immune System ◽  
Live Weight ◽  
Innate Immune ◽  
Nonspecific Resistance ◽  
Pathological Conditions ◽  
Iron Deficient ◽  
Hemostatic Disorders

The innate immune system in mammals is closely related to the hemostatic system. In recent years, there has been an accumulation of knowledge proving that these two systems not only interact closely, but are also linked by common molecular and cellular regulatory mechanisms. The study of these mechanisms is important to develop new approaches to the correction of hemostatic disorders, infectious diseases and other pathological conditions in productive animals. Analyzed in this review are results of the use of some modern medications for the correction of hemostatic disorders and increasing nonspecific resistance in calves. The main attention is devoted to gamavit (GM) and phosprenyl (PP), which are widely used in veterinary medicine and animal husbandry. Many studies have shown a positive effect of GM and PP on the innate immune system indices in newborn calves, both in normal state and in various pathological conditions, including infectious diseases, anemia, etc. There was an increase in the phagocytic activity of neutrophils and phagocytic number, an increase in bactericidal and lysozyme activity of blood serum, a decrease in the incidence of non-specific bronchopneumonia in calves, and an increase in live weight gain during the milk growing period. Under the influence of GM and AF, in calves with iron-deficient anemia and/or dyspepsia increase of antioxidant protection was observed as well as normalization of hemostasis, reducing the risk of thrombotic complications to a minimum. The correction of anemia and normalization of the blood formula were also noted. The most effective in correcting hemostasis was GM, which was shown to normalize many impaired platelet functions. Given the fact that platelets serve as an important link in innate immunity, it can be assumed that, at least partially, the immune-stimulating effect of GM may be mediated through these cells.

scholarly journals Perinatal environment shapes microbiota colonization and infant growth: impact on host response and intestinal function

Microbiome ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
M. Selma-Royo ◽  
M. Calatayud Arroyo ◽  
I. García-Mantrana ◽  
A. Parra-Llorca ◽  
R. Escuriet ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Gut Microbiota ◽  
Intestinal Epithelium ◽  
Innate Immune System ◽  
Host Response ◽  
Innate Immune ◽  
Epithelial Barrier ◽  
Intestinal Function ◽  
Intestinal Maturation

Abstract Background Early microbial colonization triggers processes that result in intestinal maturation and immune priming. Perinatal factors, especially those associated with birth, including both mode and place of delivery are critical to shaping the infant gut microbiota with potential health consequences. Methods Gut microbiota profile of 180 healthy infants (n = 23 born at home and n = 157 born in hospital, 41.7% via cesarean section [CS]) was analyzed by 16S rRNA gene sequencing at birth, 7 days, and 1 month of life. Breastfeeding habits and infant clinical data, including length, weight, and antibiotic exposure, were collected up to 18 months of life. Long-term personalized in vitro models of the intestinal epithelium and innate immune system were used to assess the link between gut microbiota composition, intestinal function, and immune response. Results Microbiota profiles were shaped by the place and mode of delivery, and they had a distinct biological impact on the immune response and intestinal function in epithelial/immune cell models. Bacteroidetes and Bifidobacterium genus were decreased in C-section infants, who showed higher z-scores BMI and W/L during the first 18 months of life. Intestinal simulated epithelium had a stronger epithelial barrier function and intestinal maturation, alongside a higher immunological response (TLR4 route activation and pro-inflammatory cytokine release), when exposed to home-birth fecal supernatants, compared with CS. Distinct host response could be associated with different microbiota profiles. Conclusions Mode and place of birth influence the neonatal gut microbiota, likely shaping its interplay with the host through the maturation of the intestinal epithelium, regulation of the intestinal epithelial barrier, and control of the innate immune system during early life, which can affect the phenotypic responses linked to metabolic processes in infants. Trial registration NCT03552939.

scholarly journals Perinatal Environment Shapes Microbiota Colonization And Infant Growth: Impact On Host Response And Intestinal Function

2020 ◽  
Author(s):  
Marta Selma-Royo ◽  
Marta Calatayud ◽  
Izaskun García-Mantrana ◽  
Anna Parra-Llorca ◽  
Ramón Escuriet ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Gut Microbiota ◽  
Intestinal Epithelium ◽  
Innate Immune System ◽  
Host Response ◽  
Innate Immune ◽  
Epithelial Barrier ◽  
Intestinal Function ◽  
Intestinal Maturation

Abstract Background Early microbial colonization triggers processes that result in intestinal maturation and immune priming. Perinatal factors, especially those associated with birth, including both mode and place of delivery are critical to shaping the infant gut microbiota with potential health consequences. Methods Gut microbiota profile of 180 healthy infants (n=23 born at home and n=157 born in hospital, 41.7% via caesarean section [CS]) was analyzed by 16S rRNA gene sequencing at birth, seven days and one month of life. Breastfeeding habits, infant clinical data, including length, weight and antibiotic exposure, were collected up to 18 months of life. Long-term personalized in vitro models of the intestinal epithelium and innate immune system were used to assess the link between gut microbiota composition, intestinal function and immune response. Results Microbiota profiles were shaped by the place and mode of delivery, and they had a distinct biological impact on the immune response and intestinal function in epithelial/immune cell models. Bacteroidetes and Bifidobacterium genus were decreased in C-section infants, who showed higher z-scores BMI and W/L during the first 18 months of life. Intestinal simulated epithelium had a stronger epithelial barrier function and intestinal maturation, alongside a higher immunological response (TLR4 route activation and pro-inflammatory cytokine release), when exposed to home-birth fecal supernatants, compared with CS. Distinct host response could be associated with different microbiota profiles. Conclusions Mode and place of birth influence the neonatal gut microbiota, likely shaping its interplay with the host through the maturation of the intestinal epithelium, regulation of the intestinal epithelial barrier and control of the innate immune system during early life, which can affect the phenotypic responses linked to metabolic processes in infants.

scholarly journals Inflammasomes as Targets for Adjuvants

Pathogens ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 252 ◽  
Author(s):  
Konstantin Ivanov ◽  
Ekaterina Garanina ◽  
Albert Rizvanov ◽  
Svetlana Khaiboullina
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Infectious Diseases ◽  
Innate Immune System ◽  
Adaptive Immune System ◽  
Mechanisms Of Action ◽  
Innate Immune ◽  
Inflammasome Activation ◽  
Adaptive Immune ◽  
Pro Inflammatory Cytokines

Inflammasomes are an essential part of the innate immune system. They are necessary for the development of a healthy immune response against infectious diseases. Inflammasome activation leads to the secretion of pro-inflammatory cytokines such as IL-1β and IL-18, which stimulate the adaptive immune system. Inflammasomes activators can be used as adjuvants to provide and maintain the strength of the immune response. This review is focused on the mechanisms of action and the effects of adjuvants on inflammasomes. The therapeutic and prophylaxis significance of inflammasomes in infectious diseases is also discussed.

scholarly journals A new landscape of host–protozoa interactions involving the extracellular vesicles world

Parasitology ◽  
2018 ◽  
Vol 145 (12) ◽  
pp. 1521-1530 ◽  
Author(s):  
Bruno Gavinho ◽  
Izadora Volpato Rossi ◽  
Ingrid Evans-Osses ◽  
Jameel Inal ◽  
Marcel I. Ramirez
Keyword(s):  
Immune System ◽  
Infectious Diseases ◽  
Extracellular Vesicles ◽  
Innate Immune System ◽  
Translational Medicine ◽  
Embryonic Stem ◽  
Innate Immune ◽  
Host Pathogen Interaction ◽  
Cell Phenotypes ◽  
Number Of Cells

AbstractExtracellular vesicles (EVs) are released by a wide number of cells including blood cells, immune system cells, tumour cells, adult and embryonic stem cells. EVs are a heterogeneous group of vesicles (~30–1000 nm) including microvesicles and exosomes. The physiological release of EVs represents a normal state of the cell, raising a metabolic equilibrium between catabolic and anabolic processes. Moreover, when the cells are submitted to stress with different inducers or in pathological situations (malignancies, chronic diseases, infectious diseases.), they respond with an intense and dynamic release of EVs. The EVs released from stimulated cellsvsthose that are released constitutively may themselves differ, both physically and in their cargo. EVs contain protein, lipids, nucleic acids and biomolecules that can alter cell phenotypes or modulate neighbouring cells. In this review, we have summarized findings involving EVs in certain protozoan diseases. We have commented on strategies to study the communicative roles of EVs during host–pathogen interaction and hypothesized on the use of EVs for diagnostic, preventative and therapeutic purposes in infectious diseases. This kind of communication could modulate the innate immune system and reformulate concepts in parasitism. Moreover, the information provided within EVs could produce alternatives in translational medicine.

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