China
Africa
Explore chapters and articles related to this topic
Host Defense and Parasite Evasion
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
Consequently, a picture is emerging in which at least some helminth infections are initially detected by tuft cells and other damaged cells of the epithelium, resulting in the release IL-25, IL-33 and TSLP (the alarmins) (Figure 4.22). IL-25, in particular, is crucial for the activation of ILC2 cells, which then express cytokines necessary for Th-2 differentiation. Alarmins are also believed to be involved in the suppression of Th-1 responses, by inhibiting the development of IL-12-secreting dendritic cells. Basophils and mast cells are also thought to contribute to Th-2 differentiation through their release of IL-4 and basophils may participate in the inhibition of Th-1 immunity. The now-activated Th-2 cells then express high levels of IL-4 and IL-13, which generate anti-helminthic effector functions, to be discussed shortly.
Resuscitation Physiology
Published in Kenneth D Boffard, Manual of Definitive Surgical Trauma Care: Incorporating Definitive Anaesthetic Trauma Care, 2019
Injury causes a SIRS clinically much like sepsis. Multicellular animals detect pathogens via a set of pattern recognition receptors (TLRs), which recognize pathogen-associated molecular patterns (PAMPs), which in turn activate innate immunocytes. Evidence is accumulating that trauma and its associated tissue damage are recognized at the cell level by a similar cell receptor-mediated detection of intracellular products released by injured and dying cells. The term ‘alarmin’ has been used to categorize these endogenous DAMPs that signal tissue and cell damage.4 A major source of DAMPs is injury-induced release of mitochondrial products, including mitochondrial DNA, coined the ‘enemies within’. Endogenous DAMPs and exogenous PAMPS therefore convey a similar message and elicit similar responses.5 Surgical source control, whether for infection or necrotic tissue, is an attempt to minimize the host exposure to these toxic moieties.
Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Asmita Hazra, Saptarshi Mandal
As discussed in Section 5.1.4, pathogens or tissue damage produces PAMP and DAMP or alarmins. Most antimicrobial proteins are potent alarmins that activate PRR TLR or NLR and trigger the innate immune system and prime the adaptive immune system. It is becoming clear that many of the antimicrobial proteins are multifunctional, rather than pleiotropic. Many of these alarmins are charged molecules (usually positive), usually do not have a leader sequence, and thus are secreted by nonclassical secretion pathways, and can cross lipid membrane compartments. A large number of them not only activate the immune system but also modulate angiogenesis. Some examples relevant to psoriasis are briefly described below.
Blood eosinophils in COPD: friend or foe?
Published in Expert Review of Respiratory Medicine, 2022
Anastasia Papaporfyriou, Petros Bakakos, Georgios Hillas, Andriana I. Papaioannou, Stelios Loukides
Monoclonal antibodies against eosinophilic inflammation, although seeming to be a promising targeted therapy for patients with asthma, have shown poor results in the case of COPD. Whether this is a result of differences in mechanisms of eosinophilic inflammation between asthma and COPD or it is a fact that biologic therapies against eosinophilic inflammation in COPD have not a lot to offer is yet to be determined. Examining the role of type 2 innate lymphoid cells (ILC2s) and their epithelial mediators called alarmins, such as IL-33, IL-25 and thymic stromal lymphopoietin (TSLP), in COPD might provide some answers. In vitro studies and mouse models targeting these alarmins gave promising preliminary results. However, clinical trials including carefully selected patients with COPD, using different cutoff eosinophil values, might provide results on the efficacy of such therapies.
Clinical relevance of understanding mitogen-activated protein kinases involved in asthma
Published in Expert Review of Respiratory Medicine, 2020
Corrado Pelaia, Alessandro Vatrella, Claudia Crimi, Luca Gallelli, Rosa Terracciano, Girolamo Pelaia
Already available anti-asthma biological drugs include an anti-IgE monoclonal antibody (omalizumab), two anti-IL-5 monoclonal antibodies (mepolizumab and reslizumab), an IL-5 receptor blocker (benralizumab), and a dual IL-4/IL-13 receptor antagonist (dupilumab) [108–115]. Further investigational biologics have been developed against alarmins (TSLP, IL-25, IL-33) and alarmin receptors (TSLP-R, IL-25-R, ST2) [116,117]. Therefore, the above-mentioned drugs effectively work on molecular targets somehow engaged within the complex network of MAPK signaling pathways. In conclusion, the ongoing progress regarding the knowledge of the pivotal role played by MAPKs in signal transduction is significantly contributing to better understand not only the pathobiology of asthma, but also the intimate mechanisms of action underlying the pharmacologic effects of the new agents utilized for add-on treatment of severe disease.
Expression of Toll-like receptors 2 and 4 on peripheral mononuclear cells (PBMCs) after laparoscopic cholecystectomy
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2019
Justyna Agier, Katarzyna Krawczyk, Paulina Żelechowska, Elżbieta Kozłowska, Ewa Brzezińska-Błaszczyk, Magdalena Wiktorska
It is well documented that DAMPs are rapidly released following trauma and surgical injury [3,19–22]. Higher levels of HMBG1 and cell-free DNA in patients undergoing resection of colorectal liver metastases were found [21]. It was also noticed that the serum levels of alarmins, such as S100A8 and S100A12 proteins, in patients who have undergone major abdominal surgery were significantly higher compared with healthy controls [19,20]. Moreover, positive correlations between S100A8 and both IL-6 and CRP levels, that is, inflammatory-response markers, were found [19]. It is generally known that alarmins contribute to the initiation and propagation of inflammation and they are responsible for subsequent tissue repair [1–3]. Alarmins interact with cellular TLRs, and HMGB1, HSP60, HSP70, uric acid, hyaluronan, and biglycan are sense by TLR2 whereas HMGB1, HSP22, HSP60, HSP70, HSP72, biglycan, heparan sulfate, fibrinogen, and S100 proteins are ligands for TLR4 [2,8]. Thus, the expression levels of cellular TLRs, and especially TLR2 and TLR4, might strongly influence the responsiveness of cells to DAMP activation, and in this way can regulate the intensity of inflammatory response to surgical injury. Hence, further studies are necessary to clarify this issue in more detail.