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Infection and Inflammation
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Erik H. J. G. Aarntzen, Andor W. J. M. Glaudemans
In particular, macrophages release soluble factors, for example, prostaglandins, leukotrienes, and platelet-activation factor, or chemokines, which facilitate the recruitment of other immune cells [5–7]. For example, tumour-necrosis factor α (TNFα) is an activator of endothelial cells; interleukin-8 (CXCL8) is involved in the recruitment of neutrophils to the site of infection, and interleukin-1β (IL-1β) and interleukin-6 (IL-6) induce systemic acute-phase responses in the liver. Antibody-antigen complexes and surface molecules on pathogens can induce the activation of other, non-eukaryotic, components of the immune system; the complement system, and platelets [8, 9]. The complement system consists of plasma proteins that react to mark pathogens for phagocytosis, a process called opsonization, and help exaggerate immune response.
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
The complexity of the complement system is one reason the immune system is difficult to model. The complement system consists of about 20 soluble proteins; however, the reactions of the first 11 are best known. The complement system is activated by either the classical pathway or the alternate pathway. In the classical pathway, an Ab binds to an Ag, and a specific Fc site becomes uncovered. This Fc site can bind with the CI molecule of the complement system, initiating a complex cascade of complement reactions, shown schematically in Figure 10.4. Some of the products of the classical cascade are immunocytokines that have activating effects on immune system cells. For example, the complement component, C3b, strongly stimulates phagocytosis by macrophages and neutrophils. They engulf the bacteria to which the Ab-Ag complexes are attached in a process called opsonization. Another important product of the complement reactions is C5b6789. This product does lysis, i.e., it ruptures cell membranes similar to perforin secreted by NK cells and CTLs.
Basic Chemical Hazards to Human Health and Safety — II
Published in Jack Daugherty, Assessment of Chemical Exposures, 2020
The complement system is a whole set of proteins that destroy cell membranes, attract phagocytes, and stimulate the immune system. Cells undergoing viral attack produce interferon, which stimulates healthy cells to produce antiviral proteins. The latter interferes with the process of viral replication, slowing down the viral attack, allowing the body’s immune system a chance to catch up with defenses. Macrophages release proteins called pyrogens that produce the fever accompanying viral infections. The inflammatory response is the last line of defense. Connective tissue cells called mast cells, upon sensing the presence of cell damage, produce histamine, which causes vasodilation, increases blood vessel permeability, and attracts all defenders, such as macrophages, neutrophils, eosinophils, complement proteins, and other protein defenders to aid in the removal of debris. Vasodilation increases the blood flow to the area, making the arrival of defense forces easier, but also producing the classical signs that an inflammation is present: heat, redness, pain, and swelling.
PEGylated liposomes: immunological responses
Published in Science and Technology of Advanced Materials, 2019
Marwa Mohamed, Amr S. Abu Lila, Taro Shimizu, Eman Alaaeldin, Amal Hussein, Hatem A. Sarhan, Janos Szebeni, Tatsuhiro Ishida
It is well known that the complement system is responsible for immune regulation in the body; it contributes to coordination of the adaptive immune response, and it plays a pivotal role in the immune defense against foreign intruders [85]. Complement activation as a possible cause of HSRs, caused by radiocontrast media, was reported as early as the 1970s [86,87]. Hugli [88] studied complement activation and described the structures and roles of anaphylotoxins, primarily C3a and C5a, in complement-mediated adverse drug reactions. In animal studies, interestingly, they discovered that C3a and C5a are effective regulators in autonomic and cardiovascular organ function. Moreover, they suggested that over-expression of C3a and C5a in complement activation explains the cardiovascular symptoms and other symptoms of anaphylactic reactions [77]. Szebeni reported that CARPA is an independent class of type I reactions, exhibiting receptor-mediated mast cell activation [76]. Several drugs and agents cause CARPA, including radiocontrast media, liposomal drugs (Doxil®, DaunoXome® and Ambisome®), and micellar solvents such as the excipient Cremophore EL present in Taxol) [76,77,89,90].
A human whole-blood model to study the activation of innate immunity system triggered by nanoparticles as a demonstrator for toxicity
Published in Science and Technology of Advanced Materials, 2019
Kristina N Ekdahl, Karin Fromell, Camilla Mohlin, Yuji Teramura, Bo Nilsson
The primary function of the complement system is to act as a purging system that removes agents that do not belong in the body such as pathogens, antigen-antibody complexes, and apoptotic cells. It consists of ≈50 proteins that are soluble in blood plasma or expressed on cells where they act as receptors and regulators that protect autologous tissue against complement attacks. Schematically, the system is divided into three activation pathways known as the classical, the alternative, and the lectin pathway. Each pathway is activated by proteins which recognize structures (often carbohydrates) expressed on pathogens, apoptotic or ischemic cells, but not on healthy autologous cells. This leads to the formation of two different enzyme complexes, so-called C3 convertases, both mediating proteolytic cleavage and activation of C3, which is the central and most abundant component of the system. It is an asymmetric cleavage that gives rise to the smaller anaphylatoxin C3a and the larger fragment C3b that can bind covalently to amino acids or carbohydrates on the target particle and thereby facilitates its phagocytosis. Further activation of the complement system leads to cleavage of C5 to the anaphylatoxin C5a (even more potent than C3a), and C5b which is the basis for the formation of the multi-molecular complex C5b-9 or membrane attack complex (MAC) which can perforate the membrane on sensitive cells or pathogens thereby destroying them. C5b-9 also exists in a soluble form (sC5b-9) that can activate endothelial cells (ECs). The main function of the anaphylatoxins is to recruit and activate PMNs and monocytes and thereby prepare them to perform efficient phagocytosis.
Peat smoke inhalation alters blood pressure, baroreflex sensitivity, and cardiac arrhythmia risk in rats
Published in Journal of Toxicology and Environmental Health, Part A, 2020
Brandi L. Martin, Leslie C. Thompson, Yong Ho Kim, Charly King, Samantha Snow, Mette Schladweiler, Najwa Haykal-Coates, Ingrid George, M. Ian Gilmour, Urmila P Kodavanti, Mehdi S. Hazari, Aimen K. Farraj
Exposure to low peat produced a systemic inflammatory response characterized by a rise in LDL cholesterol relative to filtered air controls, and several differences from exposure to high peat, including elevated levels of serum LDL cholesterol C3, C4, and ACE and whole blood WBC counts. Exposure to fine PM air pollution was previously associated with increased LDL levels in children (McGuinn et al. 2020) and the elderly (Mao et al. 2020) and is a significant risk factor for cardiovascular disease. On the other hand, evidence regarding components of the complement system after air pollution exposure is mixed with some studies showing increases (Jin et al. 2019) while others decreases (Goulart et al. 2020; Tong et al. 2019a). The complement system, a crucial player in innate immunity, consists of over 30 effector molecules including C3 and C4, which promote inflammation, opsonize cells and immune complexes, and directly kill pathogens or injured cells (Noris and Remuzzi 2013). ACE, an enzyme that converts angiotensin I to angiotensin II, a potent vasoconstrictor (Ghelfi et al. 2010), also plays a key role in the adverse health effects attributed to air pollution. Ghelfi et al. (2010) demonstrated that pretreatment with an ACE inhibitor prevented cardiac dysfunction and oxidative stress responses mediated by inhalation to ambient PM in rats. Further, elevated circulating WBC counts were correlated with occupational exposure to ambient air pollution in commercial drivers (Lawin et al. 2018) and exposure to indoor air pollution due to cookstove biomass burning (Rabha, Ghosh, and Padhy 2018). The magnitude of the systemic inflammatory response is consistent with our previous peat smoke study (Martin et al. 2018), wherein there were few changes in circulating indicators of inflammation including alpha(1)-acid glycoprotein and alpha-2-macroglobulin, which dominate the acute phase response in rats. Although these changes in markers of inflammation are generally small in magnitude, in aggregate these point to an enhancement of systemic inflammation that may have influenced the functional responses observed. Although the lack of systemic inflammatory responses one day after exposure to high peat may reflect a true absence of an inflammatory response, it is possible that such a response peaked soon after exposure and waned by one day post-exposure. Future studies need to examine time-dependent changes in circulating markers to more comprehensively elucidate potential mechanisms of action.