Home | | Medical Immunology | Interaction of IgE with Cell Surface Receptors

Chapter: Medical Immunology: IgE-Mediated (Immediate) Hypersensitivity

Interaction of IgE with Cell Surface Receptors

Two types of Fc receptors reacting with IgE molecules have been characterized.

Interaction of IgE with Cell Surface Receptors

Two types of Fc receptors reacting with IgE molecules have been characterized.

A unique high-affinity receptor designated as Fcε -RI, expressed on the surface of ba-sophils and mast cells. Most IgE antibodies interact with this receptor and become cell-as-sociated soon after secretion from plasma cells.

The structure of the Fcε -RI is unique among the well-characterized lymphoid cell re-ceptors. It is composed of three subunits: a heterodimer formed by the interaction of two chains (α and β), and a homodimer of a third type of chain (γ chain). The whole molecule is therefore designated as αβγ 2 (Fig. 21.5). The external domain of the α chain binds the Fc portion of IgE. The β and γchains function as signal transduction units. Both of them contain ITAM motifs . Cross-linking of the Fcε -RI results in activation of the protein kinase Lyn, which phosphorylates ITAM tyrosines, leading then to the activa-tion of other protein kinases, such as Syk, as well as of the integral membrane linker molecule LAT . The phosphorylation of Syk and LAT is followed by ac-tivation of signaling cascades, which eventually lead to the release of performed granules and to the expression of a variety of genes coding for cytokines, enzymes, etc.

The interaction between the Fcε -RI and IgE is consistent with a simple bimolecular forward reaction and a first-order reverse reaction:

The affinity constant of the interaction, KA=k1/k-1 ranges from 108 to 1010 M/L -1. Because of the high affinity of the interaction between IgE and this Fcε -RI, IgE binds rapidly and very strongly to cells expressing it and is released from these cells very slowly. Passively transferred IgE remains cell-bound for several weeks in the skin of normal hu-mans. Because the mast cells and basophils do not produce IgE molecules, there is no clonal restriction at the mast cell/basophil level. Therefore, if the patient produces IgE an-tibodies to more than one allergen, each basophil or mast cell may bind IgE antibodies of different specificities.

The interaction between IgE and Fcε -RI does not result in cell activation. IgE serves as an antigen-receptor for mast cells and basophils. Receptor-bound IgE discriminates among antigens, binding exclusively those to which the patient has become sensitized. Re-ceptor-bound IgE must be cross-linked in order for basophils and mast cells to release their intracellular mediators (Fig. 21.6). The physiological cross-linking agent is the allergen, which is multivalent. Cross-linking of receptor bound IgE can also be induced with anti-IgE antibodies or with their divalent F(ab')2 fragments. Unoccupied receptors may be cross-linked with aggregated Fc fragments of IgE. In contrast, mast cells and basophils with IgE-antihapten antibodies on their membranes, cannot be stimulated by soluble, univalent, haptens, because those are unable to cross-link membrane IgE molecules. Stimulation is only possible when carrier-bound haptens are used, because those can cross-link many IgE molecules.

All the types of cross-linking listed above are equally efficient in activating IgE-car-rying mast cells and basophils. The details concerning the sequence of events in the ensu-ing activation cascade are still under investigation. The consequences of activation, how-ever, are well known: release of granule contents into the extracellular space and activation of the synthesis of additional mediators.

Cross-linking of receptor-bound IgE is not the only signal leading to the liberation of mediators from basophils and mast cells; these cells also respond to C3a, C5a, basic lyso-somal proteins, kinins, and autoantibodies of the IgG isotype directed against the subunit of the Fcε -RI (these autoantibodies are detected in 40% of the patients with chronic idio-pathic urticaria). It is apparent that there are multiple pathways for mast cell activation and that the participation of cell-bound IgE is not always needed.

Fcε -RII (CD23) is expressed on the membrane of lymphocytes, platelets, eosinophils, and dendritic cells and binds IgE with lower affinity than Fcε -RI. The role of Fcε -RII on dendritic cells has been previously discussed, and it is supposed to be involved in targeting eosinophils to parasites in one of the different variations of ADCC; its effect on platelets and lymphocytes is unclear.

Study Material, Lecturing Notes, Assignment, Reference, Wiki description explanation, brief detail
Medical Immunology: IgE-Mediated (Immediate) Hypersensitivity : Interaction of IgE with Cell Surface Receptors |

Privacy Policy, Terms and Conditions, DMCA Policy and Compliant

Copyright © 2018-2024 BrainKart.com; All Rights Reserved. Developed by Therithal info, Chennai.