Immunologic Mechanisms in Renal Disease
Robin S. Goldstein in Mechanisms of Injury in Renal Disease and Toxicity, 2020
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).
Pathogenesis of Tuberculosis
Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies in Clinical Tuberculosis, 2020
Swartz et al. have observed that different species of mycobacteria vary in their extent of ingestion by blood monocytes.38Mycobacterium avium complex was taken up by many monocytes, whereas MTB, Mycobacterium kansasii, and other mycobacteria were taken up by fewer monocytes. Serum was found to be important for the uptake of M. avium complex and to a lesser extent for MTB. Complement played a major role in this effect of serum.38 Complement receptor 1 (CR1) and CR3 mediate phagocytosis of virulent MTB by blood monocytes, and the C3 component of complement is the bacterial-bound ligand.39 More recently, Schlesinger et al. have shown that avirulent and virulent MTB are comparable in adherence and phagocytosis by macrophages, and thus phagocytosis alone is not a determinant of virulence.40 Other host molecules shown to have roles in phagocytosis of MTB are the mannose receptor and cell surface fibronectin (reviewed in ref.41); the MTB ligands for these molecules are LAM and the cell wall 30 kDa Ag, respectively.
The Role of β2 Integrins in Leukocyte Adhesion
Yoshikazu Takada in Integrins: The Biological Problems, 2017
The importance of the β2 family of integrins was discovered as the result of unraveling an “experiment of nature”.2 A series of reports had appeared in the medical literature describing children with a pathogenetically uncharacterized immunodeficiency. These children typically experienced recurrent bouts of life-threatening bacterial infections, often resulting in death in infancy. In vitro testing demonstrated impaired neutrophil function. Both the Fc-receptor and CR1 (complement receptor type 1, the receptor for C3b, one of the degradation products of the third component of complement) functioned normally. Whole cell lysates of detergent solubilized neutrophils from these children, normally. Whole cell lysates of detergent solubilized neutrophils from these children, when run on SDS-polyacrylamide gel electrophoresis, were missing a prominent band found in normal controls.3 Monoclonal antibodies were raised against this band which revealed this protein to be the αM subunit. Fluorescence analysis of leukocytes from these children, surface labeled with monoclonal antibodies (MAb) to the αL, αM, and αX subunits, as well as the β2 subunit, revealed that these leukocytes were missing the three β2 heterodimers.4,5
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.
Herpes simplex virus type 1 and Alzheimer’s disease: link and potential impact on treatment
Published in Expert Review of Anti-infective Therapy, 2019
Roberta Mancuso, Mariaconcetta Sicurella, Simone Agostini, Peggy Marconi, Mario Clerici
Another group of susceptibility genes for AD are genes involved in the host immune response against infection. In particular: 1) clusterin inhibits the formation of the membrane attack complex (MAC), usually activated by infection, by interacting with several of its components [131]; 2) complement receptor 1 (CR1) binds complement C3 components, blocking the complement pathway and preventing the formation of MAC [132]. Interestingly, the HSV-1 glycoprotein C is a CR1 mimics and it binds the complement C3 components, turning off the complement pathway.
Complement system network in cell physiology and in human diseases
Published in International Reviews of Immunology, 2021
Roberta Romano, Giuliana Giardino, Emilia Cirillo, Rosaria Prencipe, Claudio Pignata
Four receptors are part of the complement system. Complement Receptor 1 is expressed on macrophages and red blood cells whose role is to promote the clearance of immune-complexes; Complement Receptor 2 is expressed on B cells where, upon binding of the fragment C3d opsonizing antigens, it enhances B cell receptor signaling. Complement Receptor 3 and Complement Receptor 4, belonging to beta-2 (CD18) integrin family [14], are expressed on monocytes, dendritic cells and macrophages and take part to opsonization and phagocytic process.
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