Host Defense II: Acquired Immunity
Constantin A. Bona, Francisco A. Bonilla in Textbook of Immunology, 2019
Early investigators of anti-bacterial humoral immunity identified several functional properties of antibodies: Opsonins are antibodies which enhance the ingestion of bacteria via phagocytic cell receptors for IgG (FcγR, Chapters 4 and 10).Agglutinins cause the agglutination of bacteria in suspension, and enhance clearance from tissues and the circulation (Chapter 4).Bacteriolysins activate complement and cause bacterial cell lysis (Chapter 10). In some cases antibody and complement are sufficient to cause lysis, in other instances, they render cell wall components accessible to the destructive activity of lysozyme which delivers the coup de grace.Precipitins cause the precipitation and neutralization of bacterial exotoxins (Chapter 4).Immobilizing antibodies bind to flagellae and prevent bacterial movement and spread of infection.IgG antibodies may also activate antibody-dependent cell-mediated cytotoxicity (ADCC, Chapter 10), which may kill cells harboring bacteria replicating intracellularly.
Engineered Nanoparticles for Drug Delivery in Cancer Therapy *
Valerio Voliani in Nanomaterials and Neoplasms, 2021
When nanoparticles enter the plasma, opsonization (i.e., the adsorption of serum proteins) will occur immediately on their surfaces [5, 160a]. Through opsonization, foreign organisms or particles will be coated with nonspecific proteins known as opsonins to generate a corona and make the particles more visible to the phagocytic cells in the MPS. Opsonins typically contain complement proteins and immunoglobins (usually IgG) along with albumins, fibronectins, fibrinogens, and apolipoproteins [194]. Studies have shown that the corona has a layered architecture. It starts with an inner layer of proteins that strongly adsorb onto the surface, with Kd 10−6 to 10−8 m, to form the hard corona, which is then surrounded by a layer of soft corona formed by weak interactions [169, 195]. The primary driving forces for opsonization are based on hydrophobic and electrostatic interactions, together with entropic and conformational changes for the adsorbed proteins [196]. Depending on the charge and hydrophobicity of the nanoparticles, opsonization can occur within minutes. Experimental results suggest that a charged surface tends to be covered by proteins more rapidly than their counterparts with a neutral surface [160a].
Inherited Defects in Immune Defenses Leading to Pulmonary Disease
Stephen D. Litwin in Genetic Determinants of Pulmonary Disease, 2020
Phagocytes, including alveolar macrophages, circulating monocytes, and PMN leukocytes, possess bactericidal mechanisms. Interaction between microbes, opsonizing humeral factors, and the phagocytic surface membrane results in phagocytosis. The term opsonin includes specific antibacterial antibodies, complement components, and other cofactors. As would be expected, hypogammaglobulinemia and complement deficiencies seriously impair the opsonizing capacity of serum. Opsonized bacteria are ingested within a phagocytic vacuole and then killed intracellularly. The microbicidal mechanism involves an increase in oxygen consumption and glucose consumption by the phagocytic cell, and participation of the hexose monophosphate shunt. Mechanisms of phagocytosis and bacterial killing are covered in other monographs of this series.
Transferrin decorated PLGA encumbered moxifloxacin nanoparticles and in vitro cellular studies
Published in Drug Development and Industrial Pharmacy, 2023
Gayathri Aparnasai Reddy, Mayank Handa, Debapriya Garabadu, Ravindra Kumar, Pramod Kumar Kushawaha, Rahul Shukla
Polymeric NPs like PLGA, polycaprolactone, and poly lactic acid, when administered via the intravenous (IV) route, are rapidly uptake by the mononuclear phagocytic system (MPS). Furthermore, opsonin attachment on the surface of the NPs results in recognition by phagocytosis. It results in the elimination of NPs from the body due to the reticuloendothelial system (RES) when administered IV [16,19]. Hence, to prevent the rapid uptake by RES, PEGylation helps the NPs to escape from the RES system. Masking with PEG provides hydrophobicity to polymeric NPs by its adsorption on the surface of NPs. Moreover, delivering the drugs to the targeted site is desirable rather than the nonselective delivery of these cargos [20]. However, size of NPs plays a prominent role in RES uptake and inhibition. The size below 200 nm bypasses the RES and inhibits the need of PEGylation. To impart targeting to NPs, effective coating with ligands can be done.
Lung macrophages: current understanding of their roles in Ozone-induced lung diseases
Published in Critical Reviews in Toxicology, 2020
Sonika Patial, Yogesh Saini
The mechanisms by which O3 compromises phagocytosis are, however, not understood. Interestingly, S. zooepidemicus was found to develop a virulence factor, antiphagocytic capsulation, within 3 h of O3 exposure at 0.4–0.8 ppm that resisted phagocytosis by AM (Gilmour et al. 1993). O3 is known to impair the structure and function of SPA, an opsonin that is important for the phagocytic ability of macrophages (Stringer and Kobzik 1996; Benne et al. 1997; Tenner 1998; Schagat et al. 2001), thus compromising opsonin-mediated phagocytosis in the alveolar spaces (Oosting et al. 1991; Su and Gordon 1996). In fact, O3-exposed SPA-deficient mice exhibit severely compromised clearance of K. pneumonia (Mikerov, Gan, et al. 2008; Mikerov, Haque, et al. 2008) suggesting that SPA acts as a critical modulator of host defense against bacterial infections. Haque and colleagues reported that SPA plays a critical role in scavenging O3-induced reactive oxidants, thus mitigating oxidative stress, a protective response that was found to be absent in SPA knockout mice (Haque, Umstead, Ahn, et al. 2009). However, the effects of O3 on other opsonins and phagocytosis-related receptors remain largely unknown.
Tf ligand-receptor-mediated exenatide-Zn2+ complex oral-delivery system for penetration enhancement of exenatide
Published in Journal of Drug Targeting, 2018
Liping Zhang, Yanan Shi, Yina Song, Dongyu Duan, Xuemei Zhang, Kaoxiang Sun, Youxin Li
After NPs enter the circulation, they are adsorbed by plasma opsonins. The latter can adsorb foreign substances and accelerate the phagocytosis of these substances via the reticuloendothelial system (RES). The most important opsonins are complement and immunoglobulins. The RES can recognise opsonins specifically. Hence, most NPs adsorbed onto opsonins are recognised by the RES and are ‘swallowed up’ by phagocytic cells to reach the target organ. Targeted protein modification can selectively guide NPs to the target organ, reduce the phagocytosis of NPs by the RES, and prolong the circulation time in vivo. In our study, Dir-labelled Tf-NPs uptake by the liver and spleen was reduced, and prolongation in the circulation of Tf-NPs was obvious. Biodistribution studies revealed Dir-labelled NPs to be distributed in the heart, liver, spleen, lungs, kidneys, stomach and intestine after oral administration for 6 h, whereas Dir-labelled Tf-NPs were distributed mainly in the small intestine. Tfs targeted the small intestine; the TfR reduced NPs phagocytosis by the RES and prolonged the circulation time in the body.
Related Knowledge Centers
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