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Idiotypes and T Cell Selection
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Bjarne Bogen, Zlatko Dembić, Siegfried Weiss
The high concentration of Ig (50–270 μg/ml) needed for deletion is surprising, especially since the transgenic TCR is expressed in higher than normal amounts on double positive thymocytes which therefore should be more sensitive to deletion than normal thymocytes. Most likely, the high concentration requirement could be due to resistance of complete Ig to processing by thymic APC, as previously observed in vitro for splenic APC [19,29,30]. Alternatively, those isotypes already investigated (IgG2b, IgG3, IgA) require a high concentration for deletion, while isotypes not yet tested (i.e., IgM, IgD, IgG1, IgG2a, IgE) may be more efficient at inducing deletion. Finally, TCRs may differ in their concentration requirement for deletion: Perhaps the transgenic TCR used in the present experiments requires a particularly high Igλ2315 concentration for deletion to occur. In another model, in which the transgenic TCR recognizes an IgG2ab allotype, <0.003 μg/ml failed to induce thymocyte deletion (higher serum concentrations were not tested [80]). IgG may have a peculiar high concentration requirement for inducing deletion [51,80] because in a C5-specific TCR-transgenic model, 50/ıg/ml of C5 sufficed for deletion of single positive (but not double positive) thymocytes (lower concentrations of C5 were not tested [81]).
Paracoccidioidomycosis
Published in Rebecca A. Cox, Immunology of the Fungal Diseases, 2020
Beatriz Jimenez-Finkel, Angela Restrepo-Moreno
A correlation between isotype-specific antibodies and clinical forms of the disease has recently been established in untreated, newly diagnosed patients.79 Serum IgG levels were significantly higher in all patients, especially in those with the acute progressive form of paracoccidioidomycosis. IgM levels were always normal but, contrary to other studies, IgA levels were found to be elevated. Anti-P. brasiliensis IgG, IgA, and IgM antibodies were detected in 97%, 32%, and 45% of all patients, respectively. There was a sharp tendency towards higher levels of specific anti-P. brasiliensis IgG antibodies among those patients with the acute progressive form (i.e., 83% of patients) when compared to patients with localized, chronic disease involving a single or multiple organ systems (i.e., 60% and 55%, respectively). These data demonstrate that there is a polyclonal activation of the humoral immune system in this mycosis. The more severe the disease, the higher the antibody response, especially of the IgG isotype.
Primary Immunodeficiencies
Published in Gérard Chaouat, The Immunology of the Fetus, 2020
Alain Fischer, Durandy Anne, Claude Griscelli
This disease is marked by an extremely high concentration of serum IgE associated with bacterial infections that do not induce expected inflammatory reactions. The disease is supposed to be due to a diverted Ig isotype response following antigen stimulation. The presence mainly of antibodies of the IgE isotype may lead to the activation of mastocytes and basophils, leading to immediate hypersensitivity-type reaction. The release of substances such as histamine could impair PMN Chemotaxis and inflammatory response. This postulated physiopathological scheme remains, however, to be demonstrated.
How do nuclear factor kappa B (NF-κB)1 and NF-κB2 defects lead to the incidence of clinical and immunological manifestations of inborn errors of immunity?
Published in Expert Review of Clinical Immunology, 2023
Nazanin Fathi, Hanieh Mojtahedi, Marzieh Nasiri, Hassan Abolhassani, Mahsa Yousefpour Marzbali, Marzie Esmaeili, Fereshte Salami, Furozan Biglari, Nima Rezaei
Antibody CSR is critical for more effective responses of the humoral immune. Although mature naive B cells make IgM antibodies or exhibit IgM as a surface BCR, IgM’s effector capabilities are very constrained. IgG and IgA are isotype-switched antibodies that can neutralize toxins and restrict infectious considerably more effectively than IgM. Current vaccines frequently develop isotype-switched antibodies, which have protective effects. The BCR cannot produce CSR without co-stimulation, according to the prevalent theory of Class-switch recombination (CSR) induction. For T-cell dependent (TD) antigens, CD40 ligand (CD40L) provides co-stimulatory signals, which are forwarded by activated T cells, or TLR ligands, which are either expressed by pathogens or adjuvants for antigens that are T-cell independent (TI). Stimulation of the BCR results in the activation of the transcription factor NF-κB1. NF-κB1 p50/RelA also stimulates the transcription of NF-κB2 p100. The p50/RelA and p52/RelB complex, together with other factors, induce activation-induced deaminase (AID) transcription. Notably, activation of NF-κB2 is required for the BCR signaling that induces CSR but not necessarily for TLR4 or CD40 [54]. So, the collaboration of both NF-κB1 and NF-κB2 leads to AID expressions. Defects in the components of these pathways, such as NF-κBs, could lead to hypogammaglobulinemia, as the experimental model showed that p50−/− primary mouse showed defects in B cells in AID expression and CSR [55].
Immunological Role of IgG Subclasses
Published in Immunological Investigations, 2021
Cecilia Napodano, MariaPaola Marino, Annunziata Stefanile, Krizia Pocino, Roberto Scatena, Francesca Gulli, Gian Lodovico Rapaccini, Stefano Delli Noci, Giovanna Capozio, Donato Rigante, Umberto Basile
Aimed to elucidate IgG subclass involvement in the immune-pathogenesis of diseases, this manuscript reviews the current literature data related to IgG subclasses distribution in a number of disorders. Different reports have shown a different distribution in patients with autoimmune diseases (Basile et al. 2018; Bijl et al. 2002; Engelhart et al. 2017; Gulli et al. 2020; Hamano et al. 2001; Niks et al. 2008; Zhang et al. 2015). Many reports suggest that the nature of antigens may drive and regulate the production of each IgG subclass (Valenzuela and Schaub 2018; Zhang et al. 2015). Each IgG isotype displays different biological and functional properties: the subclass distribution may therefore regulate the outcome of immune-mediated and autoimmune diseases (abolhassani H, 2015). However, it should be noted that serum levels of IgG subclasses do not necessarily correlate with the amount of antibody deposition in the tissues.
B cells and upper airway disease: allergic rhinitis and chronic rhinosinusitis with nasal polyps evaluated
Published in Expert Review of Clinical Immunology, 2021
Harsha H Kariyawasam, Louisa K James
Although not typically associated with mucosal immunity, IgG plays an important role in immune defense in the airways. IgG makes up a significant proportion of the switched B cells in SLOs including the tonsils and makes up around half of all serum antibodies. IgGs are monomeric and through interactions with IgG receptors have diverse effector functions [63]. IgG1 and IgG3 bind to IgG receptors with high affinity and can effectively activate the complement. In contrast, IgG2 and IgG4 bind less effectively to IgG receptors and poorly activate complement. IgG2, which comprises around 16% of serum antibodies, is the main subclass of antibody induced in response to bacterial polysaccharides, whereas IgG4 which comprises just 3% of serum antibodies is typically associated with T2 inflammation and is induced following chronic antigen exposure [64]. IgE is the least abundant isotype in humans making up less than 0.01% of serum antibody in non-atopic individuals. This is partly attributed to the poor survival of IgE switched B cells in the environment of the germinal center. IgE-switched B cells are prone to rapid apoptosis [65] and those that do not undergo this fate rapidly differentiate to plasma cells [66]. As this limits the ability of IgE switched cells to undergo somatic hypermutation, it has been suggested that IgG-switched cells can serve as a ‘memory compartment’ for IgE, generated through sequential class switching [67]. As discussed in more detail below, IgE may be considered a mucosal antibody by virtue of its localized expression at barrier sites, particularly in the context of allergic airway disease.