China
Africa
Explore chapters and articles related to this topic
Immunologic responses to various forms of allergen immunotherapy
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Umit Murat Sahiner, Mohamed H. Shamji, Sakura Sato, Ozge Soyer, Stephen J. Till, Motohiro Ebisawa, Mübeccel Akdis, Stephen R. Durham
Several studies elucidate the possible functional relevance of these inhibitory/blocking allergen-specific IgG1 and IgG4 antibodies. Bet v1-specific IgG1 and IgG4 antibodies from SCIT-treated patients inhibited basophil histamine release in an antigen-specific fashion [93–97]. Bet v1–specific IgG1 and IgG4 antibodies could compete with Bet v1–specific IgE and prevent its interaction with Bet v1 allergen. In a murine model of allergy, the inhibitory activities of IgG were mediated via the FcγRIIb receptor. Incubation of IgE, allergen, and IgG immune complexes with mouse mast cells resulted in juxtaposition or coaggregation of the FcγRIIb and FcεRI resulting in suppression of mast cell degranulation [98]. Additionally, inhibition of basophil histamine release occurred using a recombinant chimeric Fcγ-Fcε construct that potentiates FcγRIIb and FcεRI coaggregation on human basophils in vitro [99]. This inhibitory effect was dependent on immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation, resulting in the activation of intracellular phosphatases that counterbalance the influence of immunoreceptor-based activation motifs (ITAMs) within the intracellular tail of the FcεRIγ [100]. In contrast, in a human model [101,102], blockade of downstream signaling of FcγRIIb with monoclonal antibody directed against CD32 (FcγRIIb) did not block IgG-mediated inhibitory activity following birch pollen SCIT, which supports the mechanism of direct competition with IgE for allergen rather than a mechanism involving downstream inhibition of the IgE receptor signaling pathway as observed in the murine model.
Immunological Responses to Subcutaneous Allergen Immunotherapy
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2014
Mohamed H. Shamji, Stephen J. Till, Stephen R. Durham
Several studies elucidate the possible functional relevance of these inhibitory/blocking allergen-specific IgG1 and IgG4 antibodies. Bet v1-specific IgG1 and IgG4 antibodies from SCIT-treated patients inhibited basophil histamine release in an antigen-specific fashion [68–71]. Bet v1-specific IgG1 and IgG4 antibodies could compete with Bet v1-specific IgE and prevent its interaction with Bet v1 allergen. In a murine model of allergy, the inhibitory activities of IgG were mediated via the FcγRIIb receptor. Incubation of IgE, allergen, and IgG immune complexes with mouse mast cells resulted in the juxtaposition or co-aggregation of the FcγRIIb and FcεRI, resulting in the suppression of mast cell degranulation [71]. Additionally, inhibition of basophil histamine release occurred using recombinant chimeric Fcγ-Fcε construct that potentiates FcγRIIb and FcεRI co-aggregation on human basophils in vitro [72]. This inhibitory effect depended on immunoreceptor tyrosine-based inhibitory motif phosphorylation, resulting in the activation of intracellu-lar phosphatases that counterbalance the influence of immuno-receptor-based activation motifs within the intracellular tail of the FcεRIγ [73]. In contrast, in a human model [74], blockade of downstream signaling of FcγRIIb with monoclonal antibody directed against CD32 (FcγRIIb) did not block IgG-mediated inhibitory activity following birch pollen-SCIT, which supports the mechanism of direct competition with IgE for allergen rather than a mechanism involving downstream inhibition of IgE receptor signaling pathway as observed in the murine model.
Analyzing Complex Polygenic Traits
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Bernard R. Lauwerys, Edward K. Wakeland
Finally, dysregulation of pathways controlling lymphocyte activation might induce various levels of autoantibody production due to polyclonal activation of the T or B cell compartment. BAFF (B cell activation factor from the TNF family), zTNF4 or BlyS, is a novel cytokine from the TNF family that induces the activation and proliferation of B cells. Mice transgenic for BlyS have elevated levels of B-la lymphocytes, hypergammaglobulinaemia, and production of nephritogenic anti-dsDNA antibodies, presumably due to up-regulation of bcl-2 expression in B cells.85-87 Of note, serum levels of BlyS are increased in human SLE patients and correlate with autoantibody titers.88-89 Similar increases in the B-1 cell population and serum autoantibody titers were found in osteopontin transgenic mice.90 In IFN-γ transgenic mice, the production of autoantibodies is T cell dependant via apoptotic keratinocytes acting as a potential source of autoantigens.91,92 Lyn, CD22 and the thyrosine phosphatase SHP-1 are all downstream regulators of signaling through the B cell receptor. Mice deficient in these molecules display various levels of autoimmunity linked to overt polyclonal B cell activation.93 B cell hyperactivity is also expressed by mice transgenic for an anti-CD1 TCR that activates CD 1-restricted B cells or in mice expressing a CD40-ligand transgene on B cells.94 Finally, PD-1, a cell-surface receptor belonging to the immunoglobulin superfamily and containing an immunoreceptor tyrosine-based inhibitory motif, has been shown to inhibit the proliferation of activated T cells. Mice deficient in PD-1 develop a lupus-like arthritis and glomerulonephritis with predominant IgG3 deposition.95
Lessons from transmissible cancers for immunotherapy and transplant
Published in Immunological Medicine, 2022
Rafael Cardoso Maciel Costa Silva, Carolina Panis, Bruno Ricardo Barreto Pires
PD-L1 is expressed by a range of innate immune cells, like monocytes and neutrophils, endothelial cells [69], and some cancerous cells [70]. PD-L1 is an important negative regulator of T cell-mediated immune response [70] and binds to the inhibitory PD-1 receptor expressed by T cells. Upon binding, PD-L1 promotes inhibitory signaling pathways from the PD-1 ITIM motif (immunoreceptor tyrosine-based inhibitory motif). Thus, cancer immunotherapies based on anti-PD-1 are currently being used in different human clinical trials [71]. Anti-PD1 therapy contributes to tolerance break against tumor antigens, enabling T cell activation. In this sense, PD-L1 expression by DFTDs can be an essential mechanism to circumvent IFN-γ induced MHC-I expression, as both are induced by this cytokine and may explain the ability of DFTDs to keep immune response silenced in some animals, even in the presence of IFN-γ [72].
Increased frequency of TIGIT+CD73-CD8+ T cells with a TOX+ TCF-1low profile in patients with newly diagnosed and relapsed AML
Published in OncoImmunology, 2021
F. Brauneck, F Haag, R. Woost, N. Wildner, E. Tolosa, A. Rissiek, G. Vohwinkel, J. Wellbrock, C. Bokemeyer, J. Schulze zur Wiesch, C. Ackermann, W. Fiedler
Inhibitory receptors and their ligands such as programmed cell death protein 1/programmed cell death 1 ligand (PD-1/PD-L1) play a crucial role in the regulation of inflammatory responses by inhibiting T-cell effector activity. During chronic infection and cancer T cells are exposed to persistent antigen stimulation, which are often associated with loss of T-cell function and upregulation of multiple inhibitory receptors, a state called T-cell exhaustion.4 We and others have recently identified the coinhibitory receptor T-cell immunoglobulin and immunoreceptor tyrosine–based inhibitory motif (ITIM) domain (TIGIT) as a potential target for immunotherapeutic strategies in AML.5 TIGIT is expressed on (virus-specific) CD8+ and both conventional CD4+ (conCD4+) and regulatory CD4+ (regCD4+) T cells, as well as natural killer (NK) cells in chronic infections and cancer.6,7
Mucosal IgG in inflammatory bowel disease – a question of (sub)class?
Published in Gut Microbes, 2020
Tomas Castro-Dopico, Menna R. Clatworthy
The potential involvement of IgG and FcγRs in IBD pathogenesis was highlighted by the consistent identification of an activating Fcγ receptor gene variant, FCGR2A-R/H131, among associated risk loci in UC across genome wide association (GWA) studies in multiple populations.20,23 Specifically, the FCGR2A variant rs1801274 encoding a receptor with low affinity for IgG (R131) is associated with protection from UC,23 suggesting a pathogenic role for IgG. FcγRs are cell surface receptors widely expressed by innate immune cells and B cells that bind to the Fc domain of IgG antibodies.24 There are several activating FcγRs in both humans (FcγRI, FcγRIIA, FcγRIIIA, and FcγRIIIB) and mice (FcγRI, FcγRIII, and FcγRIV), whose crosslinking by IgG immune complexes or opsonized cells leads to phosphorylation of immunoreceptor tyrosine based activating motifs (ITAMs) located on the intracellular domain or on the associated common γ-chain, leading to cellular activation.25 There is also a single inhibitory receptor in both humans and mice, FcγRIIB, that contains an intracellular immunoreceptor tyrosine-based inhibitory motif (ITIM) that can recruit phosphatases to signalling synapses to dampen IgG-mediated activation signalling.