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Monoclonal Antibodies Against Murine Ia Antigens: Studies On Structure, Function, Epitopes, And Idiotypes
Published in Soldano Ferrone, Chella S. David, Ia Antigens, 2019
G. J. Hämmerling, N. Koch, R. Grützmann, N. Ade
It should be mentioned in this context that all individual mc anti-H-2 are very effective in target inhibition of CTL-mediated cytotoxicity.32–34 However, when target inhibition of individual CTL clones was investigated, it was observed that only a fraction of CTL, usually in the range of 10 to 50%, would recognize determinants defined by particular mc anti-H-2 antibodies. Hence it might be of interest to determine whether individual antigen-specific T cell clones would display different sensitivity to inhibition by mc anti-Ia or, in other words, if different restriction sites can be detected on an la molecule.
Fc Receptors
Published in Maurizio Zanetti, J. Donald Capra, The Antibodies, 1999
Killer Cell Inhibitory Receptors (KIRs) are receptors for MHC class I molecules [282]. They are expressed by NK cells [283–285] and by a subset of T lymphocytes [286]. When they recognize MHC class I molecules on the surface of target cells, KIRs inhibit cell-mediated cytotoxicity of the three types — NK cytotoxicity, ADCC and CTL-mediated cytotoxicity — triggered by NK cell receptors, FcγRIIIA and TCR respectively [287]. The intracytoplasmic domain of KIRs contains two YxxL/V motifs. When expressed in RBL cells and coaggregated with FcɛRI or with chimeric molecules having the intracytoplasmic domain of TCRζ, KIRs inhibited serotonin release as FcγRIIB did [288]. Like FcR, KIRs belong to two distinct superfamilies of molecules. Human KIRs that are members of the IgSF, and murine KIRs (Ly49) that are C-type lectins [289] were described first. The intracytoplasmic domain of murine KIRs contains one YxxL motif. Recently, lectin-like KIRs were described on human NK cells. They are heterodimers made of CD94, a transmembrane molecule whose extracellular domains bind to MHC class I molecules but which has no IC domain, associated with a molecule of the NKG2 family which may function as a signal transduction subunit [290]. NKG2A and NKG2B have two YxxL motifs in their intracytoplasmic domain.
Cancer immunotherapy using a polysaccharide from Codium fragile in a murine model
Published in OncoImmunology, 2020
Hae-Bin Park, Seong-Min Lim, Juyoung Hwang, Wei Zhang, SangGuan You, Jun-O Jin
Efficient treatment of cancer demands preferential activation of CTL-mediated cytotoxicity against cancer cells.26,27 LPS, an endotoxin produced by gram-negative bacteria, is a well-known agonist of TLR4, which induces activation of DCs in humans and mice. Although LPS promotes strong immune activation, it may cause sepsis as humans are highly susceptible to endotoxins.45 Novel adjuvants that promote cancer Ag-specific CTL activation, while having low cytotoxicity to healthy somatic cells, are desirable for effective cancer immunotherapy. LPS treatment with OVA promotes OVA-specific immune responses, as indicated by IFN-γ production and induction of cytotoxic activity against OVA-coated splenocytes. However, LPS is not suitable for use in humans, as human sensitivity to endotoxins is much higher than animals.17 CFP is a natural polysaccharide that has low cytotoxicity in humans and mice. CFP promotes activation of cancer Ag-specific T-cell immunity and exerts anti-cancer effects. Therefore, CFP may be useful in enhancing immune responses against foreign Ags in humans.
A review of the immunopathogenesis of Brucellosis
Published in Infectious Diseases, 2019
Omolbanin Amjadi, Alireza Rafiei, Masoud Mardani, Parisa Zafari, Ahmadreza Zarifian
Adaptive immunity is an antigen-specific response developing after innate immunity to eliminate Brucella and protect the host. After phagocytosis, MHC-I- and II-associated bacterial peptides are presented to T lymphocytes and peptide-MHC complex is recognized by T-cell receptors. Phagocytized bacteria activate antigen-presenting cells (APCs) to secrete IL-12 [58], which is required for differentiation of naïve T cells into T helper type 1 (Th1) cells [63]. Th1 cells produce IL-2 and IFN-γ [64] and are critical for clearance of Brucella infection [65]. Rafiei et al. showed that a high level of Th1 cells in the early stage of Brucella infection is followed in later stages by Th2 cells, producing IL-4, 5, 10 and 13 [66]. In addition to CD4+ T cells, IFN-γ is produced by CD8+, γδ T and NK cells [65]. IFN-γ is responsible for the activation of antimicrobial effects in macrophages, increasing the expression of antigen-presenting and co-stimulating molecules on APCs, mobilising cytotoxic T lymphocytes (CTL)-mediated cytotoxicity and apoptosis [67]. Thus, IFN-γ is a key cytokine in initiating the immune response against Brucella. Any disturbances of Th1 responses may lead to development of chronic brucellosis and to poor outcome. On the other hand, diminished IFN-γ production with increased in IL-5 and TGF-β production is a pathognomonic picture of development of chronic disease [68]. IFN-γ gene polymorphisms may be effective in determining the severity of, and the protection against brucellosis.
Cell encapsulation potential of chitosan-alginate electrostatic complex in preventing natural killer and CD8+ cell-mediated cytotoxicity: an in vitro experimental study
Published in Journal of Microencapsulation, 2018
Vikas Chander, Ajay K. Singh, Gurudutta Gangenahalli
Cell encapsulation by the LbL technique is widely employed nowadays in various fields of science. The objective of the present study was to reduce the NK and CTL mediated cytotoxicity which can lead to transplantation failure in clinical settings by causing the lysis of donor cells or recipient cells itself. Practical difficulties associated with finding genetically identical donors necessitate the selection of individuals through an optimum HLA matching despite the differences in genetic makeup. In the latter type of allogeneic transplantation procedure, even a minuscule difference in HLA may trigger massive immune responses towards the donor or the recipient itself. Transplant rejections are usually handled with the administration of immunosuppressive agents, such as glucocorticoid, cyclosporine, tacrolimus, etc.; however, these immunosuppressive therapies leave the immune system weakened to an extent that the cells in the graft (mainly T cells) turn offensive and lead to GvHD. We evaluated the possibility of using cell encapsulation as a measure of impeding the direct contact between the two cells. The polymers chitosan and alginate were used for cell encapsulation in a manner that did not interfere with cellular integrity and viability. FDA/PI staining and PrestoBlue assay revealed a high cell viability after encapsulation. Specifically, the PrestoBlue assay that was conducted for 72 h confirmed that the cells were metabolically active even three days after the encapsulation and that the polymers were non-toxic. Fluorochrome-conjugated polymers were used to encapsulate the K-562 cells and the shielding was confirmed through CLSM imaging. SEM images revealed that the polymers were adsorbed on the anionic plasma membrane without disturbing the morphology of the encapsulated cells. Zeta potential measurements proved that the alternate deposition of chitosan and alginate was accompanied with the change in the surface charge. Surface receptor antibody binding assay confirmed the proper encapsulation and further established that the coating effectively prevents antibody binding. However, 100% reduction in fluorescence could not be achieved in comparison with the non-encapsulated cells, probably because a few cells might have escaped the shielding process.