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The Inflammatory Response: A Bridge Between The Constitutive and Inducible Systems
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
The inflammatory response causes circulating phagocytic cells, called neutrophils, to home into the site of tissue injury. Neutrophils belong to a class of cells named polymorphonuclear leukocytes after the morphology of the nucleus in the mature cell. Inactive neutrophils survive for less than a day and in people about a hundred million of these cells die and are replaced each day. Neutrophils are armed to the teeth with weapons of biological destruction that include granules filled with acid hydrolases, myeloperoxidase, lysozyme and collagenase. Their surface is equipped with sensors (receptors) for opsonins, which are a class of molecules deposited on microbes during inflammatory and acquired immune responses, that tag them for phagocytosis. Opsonin-coated microbes are engulfed by neutrophils and taken into their cytoplasm (phagocytosed) within a bilayer lipid membrane derived from the neutrophil plasma membrane. Enzyme-filled sacs (lysosomes) within the cytoplasm of the neutrophil fuse to the phagocytic vesicle releasing their contents into the vesicle and damaging the engulfed microbe. Phagocytosis also causes the assembly of a powerful oxidase, N ADPH oxidase, on the inner side of the plasma membrane of neutrophils adjacent to the site of phagocytosis. This oxidase remains associated with the phagocytic vesicle and generates superoxide anion which is converted to hydrogen peroxide within the phagocytic vesicle. The hydrogen peroxide is in turn coverted to hydroxyl radicals and hypohalides within the phagocytic vesicle, both of which contribute to the destruction of engulfed microbes.
Blastomycosis
Published in Rebecca A. Cox, Immunology of the Fungal Diseases, 2020
The mechanisms that prompt influx of polymorphonuclear leukocytes and granuloma formation are not completely understood. At present, two elements appear to be important. One is a serum-independent chemotactic factor released by Blastomyces yeasts that stimulates migration of human neutrophils and monocytes.15 This factor is resistant to heating at 100°C for 60 min and has a molecular mass greater than 10,000 Da. Its activity is stable under alkaline but not acid conditions. The other is an alkali-soluble fraction of cell walls from a virulent strain of B. dermatitidis yeasts. Injection of this substance into mice produces a pyogranulomatous inflammatory response that is indistinguishable from the response induced by viable yeast-phase organisms.16 Inoculation of an identically prepared fraction of cell walls from an avirulent strain did elicit a suppurative response but granulomas were not detected. The disparate effect of the cell walls from these two strains may be explained by a difference in the amount of covalently bound phospholipid. The virulent strain contains 15-fold more phospholipid than does the avirulent one.17
Severe Congenital Neutropenia
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Neutrophils (or neutrocytes) are one of three types of white blood cells or leukocytes (the others being basophils and eosinophils) that possess highly lobulated nuclei with four to five separate lobes (so-called polymorphonuclear leukocytes [PMN]), and various cytoplasmic granules (lysosomes) (thus referred to as granulocytes). In hematoxylin and eosin staining, neutrophils appear neutral pink (so-called neutrophils), compared to basophils' dark blue and eosinophils' bright red appearance. With an average life span of 5–135 hours, neutrophils do not reside in normal, healthy tissues, but instead circulate inactive in the blood (making up 40%–60% of circulating leukocytes). As one of the first innate immune responders to infection, injury, or cancer, neutrophils can move within minutes to sites of inflammation to phagocytose cellular debris and any invading pathogens [2].
Role of the bone marrow microenvironment in multiple myeloma treatment using CAR-T therapy
Published in Expert Review of Anticancer Therapy, 2023
Hao Yao, Lei Cheng, Dan Chen, Qian Zhang, Ling Qiu, Shi-Hui Ren, Bai-Tao Dou, Huan Wang, Juan Huang, Fang-Yi Fan
Neutrophils, also known as polymorphonuclear leukocytes, are the most abundant immune cell population in the human peripheral circulation (Figure 1) [29]. As the first line of defense in the host, they release antibacterial peptides and immune regulatory cytokines via phagocytosis and the intracellular killing of pathogens and chemokines to mediate the innate immune response [30]. Neutrophils have different functional subtypes in both physiological and pathological states, with heterogeneity in cell lifespan, cytokine release, surface protein expression, and antibacterial responses among subgroups [31]. There are two main subgroups of TANs in the polarization state: the anti-tumor N1 type and the tumor-promoting N2 type [11]. N1 neutrophils increase the production of TNF, ICAM-1, ROS, and Fas, and downregulate the expression of arginase, thereby enhancing cytotoxicity, tumor rejection, and the anti-tumor immune response to clear tumor cells [32]. N2-type neutrophils have typical polymorphonuclear (PMN)-MDSC characteristics, showing increased expression of the tumor-promoting markers CD206 and IL-10, which are conducive to tumor growth, invasion, and metastasis [33]. Although neutrophils, as fully differentiated cells, have a short lifespan, TANs are long-lived [34]. Studies have shown that N1-type neutrophils can be polarized into the N2-type under the action of TGF-β and IFN-β [35]. Blocking TGF-β signaling or treatment with type 1 IFN induces N1-type polarization [36].
Necrotizing myositis case report and brief literature study
Published in Acta Clinica Belgica, 2020
Arthur Basso, Filip Moerman, Christophe Ronsmans, Martine Demarche
Group A Streptococci (GAS) are a virulent strain because of their capacity to produce several exotoxins of which some have ‘super antigen properties’. The streptococcal pyrogenic exotoxin A (SPEA) is responsible for a major immune response with potentially devastating consequences. The reaction causes ischemia and necrosis of infected tissue and its surrounding area through the development of microthrombi. Moreover, infection spreads more easily on necrotic tissue. M protein is a virulence factor produced by streptococci. It contributes to the invasiveness of the germ by preventing phagocytosis by polymorphonuclear leukocytes. Based on these factors of virulence, D.L. Steven proposed an explanation for the development of the streptococcal toxic shock syndrome, and necrotizing fasciitis and myositis without direct entry point [3] (Figure 1). Thus, the GAS, producing exotoxins and carrying M proteins, locally accountable for a pharyngitis, would sometimes undergo a translocation leading to bacteraemia. This phenomenon is rare and arises only in 0.3% of the pharyngitis cases caused by GAS. The strained muscle, due to the discontinuity of its fibres and the bruise, is a fertile ground enhancing bacterial growth and hence the potential development of myositis. The phenomenon is favoured by the intake of nonsteroidal anti-inflammatory drugs. It was demonstrated in vitro that GAS can develop in areas of induced muscular injuries and that this phenomenon is 10 times more frequent when taking nonsteroidal anti-inflammatory drugs [4].
Relationship between histologic chorioamnionitis and genital tract cultures in pre term labour
Published in Journal of Obstetrics and Gynaecology, 2021
Monika Thakur, Suman Lata, Aleeza Pal, Himani Sharma, Bishan Dhiman
Grade 1 Presence of one focus of at least five polymorphonuclear leukocytes.Grade 2 More that one focus of grade 1 inflammation or at least one focus of 5–20 polymorphonuclear leukocytes.Grade 3 Multiple or confluent foci of grade 2.Grade 4 Diffuse and dense acute inflammation.