Immune system and Innate Immunity
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
The functions of the components of complement include: Anti-infective functions. (i) Opsonization (coating the walls of bacteria so that they can attract and bind to phagocytic cells and be easily ingested; (ii) chemotaxis; (iii) activation of neutrophils and mononuclear phagocytes and (iv) lysis of bacteria or foreign cells (Figure 55.1).Interplay between innate and adaptive immune systems. Immunomodulation of B-cell responses to specific antigen by binding to complement receptors on the B-cell surface, resulting in enhancement of antibody responses and immunological memory.Clearance. Clearance of (i) immune complexes and (ii) apoptotic cells via C1q, C3 and C4.
The Immune System in Cutaneous Disease: the Search for a Mouse Model of the Immunopathology of Psoriasis
John P. Sundberg in Handbook of Mouse Mutations with Skin and Hair Abnormalities, 2020
Humoral mechanisms are affected by soluble mediators either specifically (antibodies) or nonspecifically (antibody complexes, cytokines). Several antibody-dependent effector mechanisms have been described: activation, cytotoxic, toxic immune complex, and anaphylactic.26 Pemphigus antibody probably contributes to pathology by stimulating production of plasminogen activators from human KC. Cytotoxic mechanisms, in which antibody reacts with surface molecules on cells or structural antigens, causing subsequent activation of complement and complement-mediated lysis and/or phagocytosis, probably contributes to the pathology of pemphigus, bullous pemphigoid, vitiligo, and some skin tumors (melanoma). Immune complexes can be deposited in the tissue through which they circulate and cause inflammation. Examples of skin diseases in which toxic complexes have been implicated are leukocytoclastic vasculitis, erythema multiforme, pemphigus, dermatitis herpetiformis, and systemic lupus erythematosus. Anaphylactic (atopic) reactions, such as atopic dermatitis, are initiated by soluble mediators, such as histamine and serotonin, released by mast cells after activation by IgE molecules reacting with antigen. These reactions can also be initiated by heat, cold, and sunlight.
Overview of hypersensitivity
Gabriel Virella in Medical Immunology, 2019
The deposition of immune complexes can take place in different organs, such as the myocardium (causing myocardial inflammation), skin (causing erythematous rashes), joints (causing arthritis), and kidney (causing glomerulonephritis). Soluble immune complexes can also be absorbed by formed elements of the blood, particularly erythrocytes, neutrophils, and platelets. Although red blood cell (RBC) absorption is usually a protective mechanism, if the amounts and characteristics of RBC-absorbed ICs are such that the regulatory function of CR1 is overridden, hemolysis may take place. Thrombocytopenia and neutropenia can also result from the activation of the complement system by cell-associated ICs. Purpuric rashes due to thrombocytopenia are frequently seen in serum sickness.
Elimination of plasma soluble antigen in cynomolgus monkeys by combining pH-dependent antigen binding and novel Fc engineering
Published in mAbs, 2022
Yuji Hori, Ken Ohmine, Hitoshi Katada, Yuki Noguchi, Kazuki Sato, Takeru Nambu, Lam Runyi Adeline, Gan Siok Wan, Kenta Haraya, Kazuhisa Ozeki, Masahiko Nanami, Tatsuhiko Tachibana, Zenjiro Sampei, Taichi Kuramochi, Junichi Nezu, Kunihiro Hattori, Tomoyuki Igawa
The composition of the antigen–antibody immune complex is likely to contribute to the strong antigen sweeping. Since the latent myostatin forms a dimer in plasma, the administration of the antibody can produce an immune complex that is composed of a few antigens and a few antibodies. Therefore, when the immune complex of pH-V3-pI(A)-N434A is formed, it can exhibit avidity binding to FcγRIIb and contain a few-fold more positive-charge residues than the antigen-free antibody. The effect of positive-charge substitutions on the immune complex is much stronger than that of the antigen-free antibody, leading to the strong antigen sweeping with a minimal effect on antibody pharmacokinetics. Based on this evidence, our novel Fc engineering seems to be advantageous for sweeping antibodies that can form immune complexes containing multiple antibodies and sweeping efficiency may be reduced in the case of monomer antigen.
Enhanced immunogenic potential of cancer immunotherapy antibodies in human IgG1 transgenic mice
Published in mAbs, 2022
Jerome Egli, Stefan Heiler, Felix Weber, Guido Steiner, Timo Schwandt, Katharine Bray-French, Christian Klein, Sebastian Fenn, Gregor P. Lotz, Eugenia Opolka-Hoffmann, Thomas E. Kraft, Laetitia Petersen, Rebecca Moser, Jonathan DeGeer, Michel Siegel, Daniela Finke, Juliana Bessa, Antonio Iglesias
Immune complexes were prepared and characterized as described previously.41 In short, a mixture containing 2 mg/ml CEA-IgG and 3 mg/ml monoclonal mIgG2a anti-idiotype antibody was prepared in histidine buffer (20 mM histidine, 140 mM NaCl, pH 6.0) and incubated for 1 h at room temperature on a shaker at 500 rpm. The ICs were characterized as previously described.41 In brief, a Waters XBridge Protein BEH SEC Guard Column, 450 Å, 3.5 μm, 7.8 mm × 30 mm and a XBridge Protein BEH SEC Column, 450 Å, 3.5 μm, 7.8 mm × 300 mm were used in a Dionax UltiMate 3000 system from Thermo Fisher Scientific GmbH (ultraviolet (UV) detector MWD-3000, auto sampler, automated fraction collector). 20 μl of centrifuged dosing solutions were injected for analysis. Phosphate-buffered saline (PBS) with 5% ethanol (v/v) was used as running buffer with a flow rate of 0.5 ml/min. Online UV detection was performed at 280 nm.
Evaluation of citrinin-induced toxic effects on mouse Sertoli cells
Published in Drug and Chemical Toxicology, 2021
Yasemin Aydin, Banu Orta Yilmaz, Nebahat Yildizbayrak, Ahu Korkut, Merve Arabul Kursun, Tulay Irez, Melike Erkan
The Cell Proliferation ELISA, 5-bromo-2′-deoxy-uridine (BrdU) kit, is a colorimetric immunoassay for the quantification of cell proliferation, based on the measurement of BrdU incorporation during DNA synthesis (Roche, Mannheim, Germany). BrdU assay was performed according to the manufacturer's protocol. Cells were seeded in 96-well plates (5 × 103 cells/well) and were treated for 24 h with CTN (25–50–75–100–125–150–175–200 µmol L–1). After exposure, the proliferating cells were labeled with BrdU for 24 h at 37 °C. After removing the experiment medium, the cells were fixed, and DNA was denatured in one step by adding FixDenat (200 μL/well) for 30 min at room temperature. Then, FixDenat was removed and cells were incubated with anti-BrdU-POD solution for 90 min at room temperature. The anti-BrdU-POD binds to the BrdU incorporated in the newly synthesized, cellular DNA. At the end of incubation, the cells were washed three times with 200 μL washing solution before adding the substrate (100 μL). The immune complexes were detected by subsequent substrate reaction. Reaction product was quantified by measuring the absorbance at 450 nm wavelength with a spectrophotometer (Thermo Scientific, Waltham, MA). The cell proliferation was calculated using the following formula:
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