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The Human Immune System Seen from a Biomedical Engineering Viewpoint
Published in Robert B. Northrop, Endogenous and Exogenous Regulation and Control of Physiological Systems, 2020
IL6 is a ubiquitous cytokine that has a number of aliases, underscoring its high degree of activity in the immune system. IL6 is also known as IFN-β2, hybridoma/plasmacytoma growth factor, hepatocyte-stimulating factor, B-cell-stimulating fac-tor-2 (BSF-2), and B-cell differentiation factor (BCDF). IL6 is a 212-amino-acid glycoprotein with a molecular weight of about 26 kDa. It is made by a wide variety of immune system cells: macrophages, mast cells, T-cells, fibroblasts, and neutrophils. IL6 receptors are found on stimulated B-cells, macrophages, hepatocytes, CD4+ and CD8+ Th cells, and fibroblasts. IL6 stimulates acute phase protein synthesis by the liver. It acts as a growth factor for B-cells and induces their final maturation into Ab-secreting plasma cells. It is involved in T-cell activation and differentiation and stimulates their production of IL2 and IL2 receptors. Interestingly, IL6 inhibits the production of TNF, limiting the acute inflammatory response. Glucocorticoids, IL4, and IL 13 inhibit the production of IL6 in monocytes (macrophages).
Clinical Effects of Pollution
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 5, 2017
William J. Rea, Kalpana D. Patel
To define the degree of systemic inflammation, substances measured are inflammatory mediators such as C-reactive protein, prostaglandin E metabolite, and heat shock protein 60; IL-10 was the selected TH2 anti-inflammatory cytokine. Given that controlled ozone exposures are associated with upregulation of mCD14 on airway macrophages and monocytes, and that a synergistic action on the CD14 effect has been suggested between PM-LPS and ozone,37 they selected mCD14, sCD14, and LPS-binding protein (LBP)38,39 to characterize the LPS-recognition complex components. LPS forms a complex with an acute-phase protein called LBP responsible for the binding and transport of LPS in the circulation.39 A major response to LPS is mediated by its interaction with CD14, a 55-kDa myeloid differentiation antigen that allows endotoxin to interact with the TLR4.39 Finally, TLR4 specifically recognizes LPS and is part of the endotoxin signaling receptor complex that initiates proinflammatory signaling. Since missense mutations such as Asp299Gly are associated with a blunted response to inhaled LPS, it was determined the allelic frequencies of Asp299Gly TLR4 polymorphism in both cohorts and included only children fully capable of responding to LPS.40 Certainly, the chemically sensitive can go down this pathway eventually causing permanent brain damage.
Optical Methods of Single Molecule Detection and Applications in Biosensors
Published in George K. Knopf, Amarjeet S. Bassi, Smart Biosensor Technology, 2018
Anna Shahmuradyan, Ulrich J. Krull
C-reactive protein (CRP) is the first acute phase-protein that is synthesized mainly by liver cells (122). This protein is a sensitive biomarker for inflammation, tissue damage, infection, cell necrosis, and some malignancies. An increase in the concentration of CRP in serum is associated with cardiovascular diseases, so it is commonly used to diagnose heart attacks, ischemic stroke, and peripheral arterial disease (122). ELISA is generally used to detect CRP. Several other methods have been developed in recent years, including immunoturbidimetry, fluorescence-based immunochromatography, electrochemical impedance immunosensors, and time-resolved immunofluorometric assay (122). While these techniques have been able to detect the protein in sera at low concentrations, they cannot detect at the ultra-low concentrations typical of real samples. Kang et al. have proposed a method for detection of CRP using single molecule detection with TIRF microscopy. Antibodies were immobilized on the surface of a gold-nanopatterned biochip. The biochip had 500-nm-diameter spots and was fabricated using electron beam nanolithography. Nanostructured gold was used to enhance the electric field intensity. The CRPs were detected in a sandwich assay format, where after binding to surface-immobilized antibodies, the proteins were also bound by fluorescently labeled antibodies. The distance between the fluorescent dye and the surface of the nanochip was optimized to minimize the quenching effect of the bulk gold and to maximize the influence of the electric field for excitation of fluorescence. Samples of CRP at zM concentrations were incubated for 4 hours to allow sufficient time for Brownian motion. The chips were then incubated with fluorescently labeled antibodies for 30 min and washed prior to imaging. The group reported single molecule detection of the CRP at 33.3 zM concentration (122). The authors did not comment on the specificity of the method and suggested application in in vivo measurements.
Ozone-induced acute phase response in lung versus liver: the role of adrenal-derived stress hormones
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Devin I. Alewel, Andres R. Henriquez, Catherine H. Colonna, Samantha J. Snow, Mette C. Schladweiler, Colette N. Miller, Urmila P. Kodavanti
The acute-phase response (APR) is a rapid host defense system characterized by the synthesis of specialized proteins that drive physiological changes to counteract stressful events (Gruys et al. 2005). Immediately following the encounter of common stressors like tissue injury or infection, pro-inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1 (IL-1), and tumor necrosis factor-α (TNF-α), are proposed to trigger the production of acute-phase proteins (APPs) (Gulhar, Ashraf, and Jialal 2020) to augment tissue repair processes and reestablish homeostasis (Cray, Zaias, and Altman 2009). The APR may also be induced by homeostatic imbalances in response to inhaled environmental pollutant exposures (Elder et al. 2004; Shannahan et al. 2012). In addition, acute psychosocial pressures that activate the hypothalamus-pituitary-adrenal (HPA) stress axis act through neuroendocrine mechanisms to induce an acute-phase event (Marsland et al. 2017). Previous reviews of APR identified the liver as the primary target of cytokine signaling and subsequent APP synthesis and regulation (Cray, Zaias, and Altman 2009; Kuscuoglu et al. 2018).
Risk factors, diagnosis and management of prosthetic joint infection after total hip arthroplasty
Published in Expert Review of Medical Devices, 2019
Syed S. Ahmed, Fahima Begum, Babar Kayani, Fares S. Haddad
ESR and CRP have been shown to be superior to other serum biomarkers for diagnosing PJI, thus placing them as the first-line screening test. CRP is an acute-phase protein synthesized by the liver, released into bloodstream few hours after tissue injury and inflammation. A review conducted showed CRP to have a 74% to 95% sensitivity, and 20% to 100% specificity. ESR indirectly measures the degree of inflammation by measuring the rate of sedimentation of erythrocytes. A rise in inflammatory proteins will cause erythrocytes to fall more rapidly, increasing the ESR. Sensitivity and specificity of ESR ranges from 42% to 94%, and 33% to 87%, respectively. In general, these biomarkers have high sensitivity but low specificity. For this reason, one cannot rely solely on them to diagnose PJI or to proceed to a second stage; instead, they should be used as an adjunct to clinical signs and symptoms of PJI [16]. It has also been shown that we cannot solely rely on CRP as a screening tool for PJI. This is especially the case in organisms that have low virulence as it may give you high false-negative rates [14].
Reallocating sitting time to standing or stepping through isotemporal analysis: associations with markers of chronic low-grade inflammation
Published in Journal of Sports Sciences, 2018
Joseph Henson, Charlotte L. Edwardson, Danielle H. Bodicoat, Kishan Bakrania, Melanie J. Davies, Kamlesh Khunti, Duncan C. S. Talbot, Thomas Yates
Low-grade inflammation has been proposed to be involved in the underlying pathogenesis of type 2 diabetes mellitus (T2DM) (Wang et al., 2013). This manifestation is thought to be a result of an ongoing acute-phase response, primarily characterised by alterations in acute-phase proteins, such as C-reactive protein (CRP) (Pradhan, Manson, Rifai, Buring, & Ridker, 2001). More specifically, mediators of inflammation which include the interleukin 6 (IL-6) family of cytokines have been proposed to affect glucose homeostasis and metabolism directly and indirectly by action on skeletal muscle cells (Kristiansen & Mandrup-Poulsen, 2005). Previous studies have established an inverse relationship between the amount of physical activity and proinflammatory cytokines in obesity, T2DM, and the metabolic syndrome (Hamer et al., 2012; Kasapis & Thompson, 2005). Therefore, the beneficial effects of physical activity may be partly mediated by changes in the adipokines profile.