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Specific Host Restance: The Effector Mechanisms
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
The binding of an antibody molecule to a parasite, in and of itself, does little damage to the parasite. Clumping may inhibit dispersal and bound antibody may block receptors important in the entry into host cells, but, perhaps more importantly, bound antibody can prepare the parasite for destruction by ingestion by several types of phagocytic cells. This process of preparing the parasite for ingestion is called opsonization. The word opsonin is from the Greek for “to prepare to eat.” Antibody of the IgG class is the most efficient opsonin of all the opsonic antibodies. There are numerous receptors for the Fc portion of IgG on all phagocytic cells. The two most important types of phagocytic cells are neutrophils and macrophages, with the latter possessing three different classes of Fc receptors, one of which has a very high affinity for IgG. These Fc receptors help the phagocyte bind to the antibody-coated parasite much more tightly. The receptors for the Fc portion of antibody and the receptors for complement products (such as ) function similarly on macrophages and neutrophils.
Phagocytosis By Human Neutrophils
Published in Hans H. Gadebusch, Phagocytes and Cellular Immunity, 2020
Many indirect techniques that rely on the altered metabolism of the cell during phagocytosis have been utilized. Thus, Johnston141 used the reduction of nitroblue tetrazolium dye as a measure of phagocytosis in his study of serum opsonins. Others have utilized the increases in oxygen consumption164 or in hexose monophosphate shunt activity as an indicator of phagocytosis.135 These techniques make the assumption that the alteration in cellular metabolism is directly proportional to the rate of phagocytosis. In many cases this is true, but extreme caution must be exercised with these procedures. We have already described that attachment per se and not ingestion may be sufficient to cause altered phagocytic metabolism.156,157,160 Further, certain surface-active agents including detergents165 and phorbol myristate acetate166 may activate cellular metabolism completely independently of phagocytosis. Finally, cells from some patients are capable of normal phagocytosis but completely lack the post-phagocytic metabolic alterations.167 Conversely, neutrophils isolated from patients infected with influenza virus have been reported to exhibit impaired phagocytosis (determined by microscopic examination) with normal post-phagocytic hexose monophosphate shunt activity.168
Inflammation
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
Lysosomal enzymes are associated with intracellular digestive functions in phagocytic cells. Neutrophil leukocytes and macrophage granules are the major sources of lysosomal enzymes in the inflammatory response. The lysosomal enzymes degrade all types of macromolecules, such as proteins, peptides, carbohydrates, nucleic acids and lipids. Some of these enzymes are presented in Table 5, showing the similarity with enzymes occurring in neutrophil granules (Table 4). All cathepsins have broad substrate specificity and occur in multiple forms with identical catalytic activity.22 Elastase and cathepsin G stimulate lymphocytes and initiate antibody production.475 Neutral lysosomal proteases cleave C and C5 fragments into active chemotactic agents488 and activate kininogen to bradykinin and plasminogen to plasmin.193 Neutrophil leukocytes contain collagenases which split GLY-ILE or GLY-LEU bonds in collagen, yielding smaller peptide fragments which are further degraded by elastase, cathepsin B, or metalloproteinase enzymes.30,268,324
Mitochondrial disruption in isolated human monocytes: An underlying mechanism for cadmium-induced immunotoxicity
Published in Journal of Immunotoxicology, 2022
Ulfat M. Omar, Ekramy M. Elmorsy, Ayat B. Al-Ghafari
The effect of CdCl2 on isolated cell ability to phagocytize 1-μm latex beads (fluorescent yellow-green carboxylate-modified polystyrene beads; Sigma) was evaluated using the method of Schroeder and Kinden (1983). In brief, the pooled monocytes were seeded at 106 cells/1 ml/well in 12-well plates and then exposed to 0, 0.1, or 1 µM CdCl2 for 6, 12, 24, and 48 hr. At the end of each timeframe, phagocytic activity of the treated cells was evaluated. For this, the cells were washed twice with PBS and then fresh culture medium containing beads (at a 10:1 bead:cell ratio) was added to each well. After 1 hr to allow the cells to phagocytize the beads (at 37 °C), the plates were gently centrifuged (225 × g, 5 min) to help separate the cells from any non-phagocytosed beads (which remain in medium supernatant). After decanting the non-ingested materials, cells were washed twice and bead-free medium was added to each well, and fluorescence in each well was measured at excitation and emission wavelengths of 440 and 485 nm (respectively) in a fluorescence microplate reader ‘TopCount’ (Perkin Elmer, Ueberlingen, Germany). All estimates for the phagocytic endpoints assessed here were normalized to the total number of remaining attached cells present in a well at the end of the given exposure to the CdCl2. All experiments were conducted in triplicate. Within each experiment, each studied treatment concentration at any timepoint was evaluated in triplicate wells in each plate.
The engineering challenges and opportunities when designing potent ionizable materials for the delivery of ribonucleic acids
Published in Expert Opinion on Drug Delivery, 2022
Yan Ming Anson Lau, Janice Pang, Grayson Tilstra, Julien Couture-Senécal, Omar F. Khan
Generally, LNPs can also be internalized via phagocytosis, a process used by cells to ingest large particles (Figure 3). The exact size cutoff for phagocytosis can be a point of debate [84], with some groups suggesting that it is ≥0.5 μm [85]. This pathway is commonly used by immune phagocytes such as macrophages, dendritic cells and neutrophils to clear pathogens, diseased cells, and foreign biologics and materials [85]. Other cell types such as epithelial cells and fibroblasts have also demonstrated their ability to phagocytose, albeit at a less efficient rate [86]. Phagocytosis is initiated by ligand binding of specific phagocytic receptors. These receptors include Fc, mannose, scavenger, and complement receptors [85]. Upon binding, a cascade of receptor signaling initiates localized changes in actin structure and the plasma membrane, forming a phagocytic cup that slowly extends to engulf the target [87]. The vesicle formed after internalization is termed a phagosome, which enters the classical endosomal pathway and eventually fuses with lysosomes to form a phagolysosome, a structure that biochemically and enzymatically breaks down the phagocytosed target [87].
Melanocortin 5 Receptor Expression and Recovery of Ocular Immune Privilege after Uveitis
Published in Ocular Immunology and Inflammation, 2022
Tat Fong Ng, Ambika Manhapra, David Cluckey, Yoona Choe, Srujan Vajram, Andrew W. Taylor
Our previous findings showed that RPE through its production of α-MSH regulates phagocytic maturation within APC that can change with disease.11 This regulation is important since phagocytic activity is linked to both the induction of inflammation and the processing and presentation of antigen, of the innate and adaptive immune interface.36 Phagocytes (macrophages, dendritic cells, and microglial cells) phagocytize proteins, dead cell material, and toxic molecules to prevent them from adversely affecting tissue structure and cell survival. As the phagosome matures it fuses with the lysosome. Within the acidic environment of the activated phagolysosome, there is an efficient degradation of proteins into peptides that can be shuttled into the MHC class II compartment. If the peptides have high affinity to the MHC class II molecule, they are loaded onto MHC class II and presented on the surface of the phagocyte that is now an antigen-presenting cell. Altering this pathway would prevent the activation of autoreactive effector T cells and be beneficial to maintaining a healthy ocular microenvironment. To suppress the phagosome maturation pathway in autoimmune disease would help to rob the autoreactive effector T cells their central driving mechanism of presented autoantigen. Since suppression of EAU by α-MSH-therapy may require MC5r-expression, we assayed whether MC5r expression is needed for α-MSH-therapy to restore RPE-regulation of phagosome maturation in EAU.