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Tumor Necrosis Factor
Published in Jason Kelley, Cytokines of the Lung, 2022
Neutrophils are not usually present in significant numbers in either the bronchial mucosa or alveolar parenchyma under physiological conditions, but appear as the most prominent inflammatory leukocyte during acute bronchitis and pneumonitis. Neutrophils express approximately 6000 high-affinity receptors per cell (Shalaby et al., 1985). TNF up-regulates neutrophil functions, such as antibody-dependent cellular cytotoxicity, phagocytosis, hypochlorous acid production, and the release of oxygen radicals and lysosomal enzymes (Shalaby et al., 1985; Klebanoff et al., 1986; Wewers et al., 1990; Sample and Czuprynski, 1991). TNF also increases complement receptor 1 and 3 expression and may, thereby, increase neutrophil adhesion and phagocytosis (Berger et al., 1988).
Pathogenicity and Virulence
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Other intracellular pathogens avoid the effects of ROls by arranging their uptake into phagocytes through alternate pathways that do not trigger the oxidative burst. Salmonella typhimurium and Yersinia spp. accomplish this by utilizing the same invasins to enter professional phagocytes that were described for their invasion of other cell types. Another large group of intracellular pathogens, including L. pneumophila, M. tuberculosis, and M. leprae, Histoplasma capsulatum, Leishmania major, and L donovani, bind abundant and i and thus ensure their uptake into phagocytes via complement receptors CR1 and CR3, respectively. Phagocytosis mediated by this process fails to evoke an oxidative burst. However, the CR3 receptor has been shown to have a second binding site specific for a lectin, and binding through this site does trigger an oxidative burst. This explains why the promastigotes of L major, which bind the CR3 lectin receptor, are readily killed within macrophages while metacyclic promastigotes, a later developmental stage that binds only the CRI receptor, are resistant to killing.
Immunologic Mechanisms in Renal Disease
Published in Robin S. Goldstein, Mechanisms of Injury in Renal Disease and Toxicity, 2020
Brian D. Schreiber, Gerald C. Groggel
Another important function of complement in immune injury is its role in the removal of immune complexes from the circulation via the complement CR1 receptor which is specific for C3b (Hebert and Cosio, 1987; Schifferli et al., 1986). In primates, immune complexes are transported to the fixed macrophage system by erythrocytes which have the CR1 receptors (Hebert and Cosio, 1987; Schifferli et al., 1986). Immune complexes which activate complement have C3b bound, and this interacts with its receptor, CR1, on the red blood cells (Schifferli et al., 1986). The erythrocyte-bound immune complexes are carried to the liver where they are removed and the erythrocyte returned to the circulation. The binding of the immune complexes to the erythrocytes prevents their deposition in organs such as the kidneys. When complement is depleted, a large proportion of injected complexes are deposited in the kidney rather than being cleared by the liver (Waxman et al., 1984). Transport of immune complexes by erythrocytes thus has a protective function which ensures their safe delivery to the mononuclear phagocyte system where they are eliminated. These findings may explain why patients with complement deficiencies have a higher incidence of immune complex-mediated diseases (Schifferli et al., 1986).
Altered levels of complement components associated with non-immediate drug hypersensitivity reactions
Published in Journal of Immunotoxicology, 2020
Feng Wang, Liping Huang, Junfeng Yu, Dandan Zang, Liangping Ye, Qixing Zhu
Interestingly, it is not clear how the complement cascade might be activated without an antibody complex in SJS and TEN patients? A previous in vitro study has shown that granzyme B could cleave complement components C3 and C5 into bioactive fragments C3a and C5a, suggesting granzyme B could induce complement activation directly (Perl et al. 2012). Considering that abundant granzyme B is secreted by CD8+ cytotoxic T-cells in SJS/TEN patients (Chung et al. 2008), we surmised that granzyme B might be one trigger for complement activation in SJS/TEN. In additon, herpesvirus re-activation, especially with Epstein–Barr virus (EBV), is associated with the pathogenesis of SJS/TEN (Ishida et al. 2014). This is of importance in interpreting the data here in that it was found that EBV infection could down-modulate expression of complement receptor type 1 (CR1) expression, a complement-regulatory protein that works with other complement factors to inhibit complement activation (Ogembo et al. 2013). Accordingly, a loss of CR1 in situ could lead to favorable conditions for complement activation and the sequelae of events that could then give rise to SJS/TEN. However, more reliable proof still needs to be obtained to support this viewpoint.
Safety of current treatments for paroxysmal nocturnal hemoglobinuria
Published in Expert Opinion on Drug Safety, 2021
The rate of extravascular hemolysis in PNH patients varies widely according to pattern of C3 split products, complement regulator molecules [61,62], and polymorphisms of the complement receptor [63]. The risk of extravascular hemolysis can be increased by polymorphisms in complement receptor 1. A study of 72 patients receiving eculizumab for hemolytic PNH found that those with the low-expression complement receptor 1 genotype (L/L) were more likely to show a suboptimal response to eculizumab than patients carrying the high-expression genotype (H/H) [63]. The effect of ravulizumab on extravascular hemolysis needs to be assessed in long-term and extension studies because ravulizumab and eculizumab have the same C5 target.
Effect of α+ Thalassemia on the Severity of Plasmodium falciparum Malaria in Different Sickle Cell Genotypes in Indian Adults: A Hospital-Based Study
Published in Hemoglobin, 2023
Prasanta Purohit, Pradeep Kumar Mohanty, Jogeswar Panigrahi, Kishalaya Das, Siris Patel
The protective effect of α+-thalassemia on Plasmodium falciparum (P. falciparum) malaria has been widely studied especially in African countries and the findings were quite contradictory [1–14]. All of these studies were focused on children except the study undertaken by Mockenhaupt et al., on Nigerian adults [3]. In many studies, α+-thalassemia has been found to be protective against severe malaria rather than getting infection [2,3,10]. Several mechanisms have been put forth to explain the association of α+-thalassemia and malaria including impairment of adherence of parasitized RBCs to microvascular endothelial cells (MVECs) and monocytes mediated by P. falciparum erythrocyte membrane protein 1 (PfEMP1), reduced expression of complement receptor-1 in red cells leading to decreased rosetting of parasitized RBCs, rapid phagocytosis of α-thalassemic RBCs by blood monocytes compared to normal RBCs raising the possibility of a greater number of parasite removal from the circulation, reduced growth, and multiplication of the parasites in α-thalassemic RBCs, and increased binding of malarial specific antibody to α+-thalassemic parasitized RBCs compared to infected RBCs with normal α-globin genotype [15–18]. Along with α-thalassemia, sickle cell hemoglobin (Hb) disorders have been found to be protective against malaria. However, the protective effect of both of these genetic disorders decreased when co-inherited together [5]. Alpha-thalassemia occurs predominantly across the tropical belt including India. It has been estimated that about 5.0% of the global population carries an α-thalassemia variant [1,19–21]. In India, the prevalence of α-thalassemia was found to be 5–80% [22–29].