Allergy: Basic Mechanisms and Tests
John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie in Basic Sciences Endocrine Surgery Rhinology, 2018
Mast cells are haemopoietic stem cell derivatives and mature locally. They reside near the surface where our body is exposed to pathogens and allergens. Based on the distribution they are known as either mucosal mast cells or tissue mast cells. They are often found in close proximity to blood vessels. FcεRI is capable of being tightly bound to sIgE even in the presence of a very low serum concentration. On exposure to their specific allergens, cross-linking of the receptor and signalling follow to produce clinical phenomena (Figure 14.1). FcεRII is a low affinity IgE receptor (CD23). It is present in many cells including B cells, activated T cells, monocytes, eosinophils, platelet and follicular dendritic cells. The role of FcεRII in an allergic reaction is not fully understood.
Immunoglobulin E: Pathogenic Relevance in Urticaria and Eczema
Ana M. Giménez-Arnau, Howard I. Maibach in Contact Urticaria Syndrome, 2014
FcεRII, also named CD23, is considered the low-affinity receptor (Figure 11.2b). It structurally corresponds to the C-type (calcium-dependent) lectin superfamily and is characterized by a three-lectin “head” domain that binds to IgE and a helical coiled-coil “stalk” region that binds to cytoplasmic membranes through the intracellular N-terminal portion. It is misnamed as a low-affinity receptor because its affinity with a single lectin domain is low; however, when IgE binds to the trimer, its affinity approaches that of the high-affinity receptor.[11] The N-terminal intracellular sequence can differ in their first seven (CD23a) or six (CD23b) amino acids, which determines in which cells will be expressed. CD23a is basically restricted to B cells and corresponds to the major regulator of IgE levels. Thereby, IgE levels become stabilized by binding IgE to CD23 on B cells as it induces negative feedback signals for IgE synthesis. Consequently, when IgE levels are high, the CD23 molecules are occupied by the IgEs decreasing the IgE synthesis. On the other hand, when IgE levels are low, CD23 molecules are mostly unoccupied and therefore enhance IgE synthesis.[11,32,33]
Immunoglobulins
Constantin A. Bona, Francisco A. Bonilla in Textbook of Immunology, 2019
The low-affinity IgE receptor, FcɛRII (or CD23), is the only well-characterized Fc receptor which is not a member of the immunoglobulin gene superfamily. FcɛRII is encoded by a gene on chromosome 19. Two transcripts have been identified, designated A and B. FcɛRIIA is found only on B cells in the developmental stage when they express both surface IgM and IgD. They cease to express CD23 when they become antibody-secreting cells. B cell FcɛRIIA is associated with major histocompatibility complex class II molecules. FcɛRIIB is found on T cells and thymic epithelial cells, monocytes, eosinophils, platelets, dendritic cells, and Langerhans cells. FcɛRIIB is not known to be part of a complex.
Targeting interleukin 4 and interleukin 13: a novel therapeutic approach in bullous pemphigoid
Published in Annals of Medicine, 2023
Fangyuan Chen, Yiman Wang, Xinyi Chen, Nan Yang, Li Li
IgE has two receptors, FcεRI and FcεRII (CD23). FcεRI is a high-affinity receptor, primarily distributed on mast cells and basophils; CD23 is a low-affinity receptor, found mainly on mature B cells and eosinophils. Both receptors are involved in stimulating the Th2 response [44]. The binding of IgE autoantibodies to mast cells and basophils induces degranulation, which is responsible for eosinophil infiltration in the BP lesions [45]. Mast cells express high levels of FcεRI for eosinophils recruitment and can produce major regulating cytokines for eosinophils like IL-5 [46]. Consistent with the distribution of receptors, Freire et al. reported that IgE autoantibodies could not only be detected in the serum of patients with BP but also in the basement membrane zone and on the surface of mast cells and eosinophils, which indicates the interaction between IgE and cells with high-affinity receptors [45]. Furthermore, there is evidence that both FcεR-dependent and -independent immune reactions promote blister development in BP, and that IgE is involved in the onset of BP [40,47–50]. For in vivo studies, Lin et al. found that the severity of the disease depends on IgE dose and is related to the degree of eosinophil infiltration in lesions [51]. In addition to inducing blister formation, the administration of IgE autoantibodies can also recapitulate similar symptoms, such as pruritus, erythema, and eosinophilia, which are absent in sole IgG-based mouse models [40,47]. This finding may explain why patients with BP often exhibit pruritic erythema and eosinophilic infiltration.
Dynamic Aspects of the Immunoglobulin Structure
Published in Immunological Investigations, 2019
Immunoglobulin E is an important participant in allergic reactions. The Fcε fragment reacts with the FcεRI receptor on mast cells, and with CD23 on B cells. The Fcε is composed of dimers from the Cε2, Cε3, and Cε4 domains, and is, by nature, flexible (Wurzburg and Jardetzky, 2009). According to crystallographic studies (Drinkwater et al., 2014), the Cε2 domains fold back on the Cε3 and Cε4 domains. The Cε3 domains react with the both cell receptors and thus play a central role in IgE’s biological activity. Isolated Cε3 have a ”molten globule” structure, retaining their flexibility within the IgE molecule (Borthakur et al., 2011; Harwood and McDonnell, 2007; Henry et al., 2000; Price et al., 2005), but is well-structured, following formation of complexes with the FcεRI receptor. The detailed structure of Fcε and its domains was elucidated at the highest resolutions by means of X-ray crystallography and by differential scanning fluorimetric analysis (Doré et al., 2017). It was found that the Cε3 domain displays intrinsic flexibility and quaternary structural variation especially in regions distant from Cε4. The reaction with the cell receptors or corresponding antibodies stabilizes the Cε3 structure. The high-mannose carbohydrate unit of Cε3 is well-ordered and makes contact with Cε4, which is not essential for cell receptor binding.
Uncommon retroperitoneal tumour: follicular dendritic cell sarcoma
Published in Acta Chirurgica Belgica, 2021
Fabio Carboni, Renato Covello, Luca Bertini, Mario Valle
FDCS is a rare malignant tumour caused by proliferation of antigen-presenting follicular dendritic cells localized within lymphoid follicles. It arises most commonly in lymph nodes of the cervical, mediastinal or axillary areas but also in extranodal sites. Pathogenesis is still unknown but association with EBV, Castlemann and autoimmune disease has been reported [1–4]. Histologically two major subtypes have been described: the common type with sarcomatoid appearance and the rare inflammatory pseudotumour like variant [4]. In the former subtype, spindle to ovoid tumour cells are arranged in storiform, fascicular or whorled patterns. The cell borders are generally indistinct and abundant eosinophilic cytoplasm is observed. They have elongated or ovoid nuclei with a thin membrane and small nucleoli. Lymphoplasmacytic infiltration is present in most cases. Beyond morphological characteristics, immunohistochemistry is commonly positive for CD21, CD35 and CD23. Clusterin and podoplanin are additional markers often positive [1,3–6]. Because of the scarcity of identified cases this tumor is probably under recognized, especially in presence of extranodal tumours.