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Basics of Allergy
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
Rafeul Alam, Dipa K Sheth, Magdalena M Gorska
Mature DC present antigenic epitopes to a specific T cell through the formation of the ‘immunological synapse’ (Dustin 2002). TCR and co-stimulatory molecules (e.g., CD4/CD8, CD28) engage with their counter ligands on APCs in the immunological synapse. The TCR is associated with the CD3 complex (composed of a, b, g, d, e and two z subunits). Proper assembly of this receptor complex is important for TCR signaling. The lack of the CD3g subunit causes severe immunodeficiency whereas that of the CD3e subunit induces a milder form of immunodeficiency. The binding of the TCR to the peptide-MHC complex results in the activation of CD4- and CD3-associated tyrosine kinases—Lck: lymphocyte specific kinase and Src: Rouse sarcoma. These kinases phosphorylate CD3-associated z chains at ITAM (immunoreceptor tyrosine-based activation motif) sites, which allow docking of multiple signaling molecules and transduction of signals through downstream pathways (Hermiston et al. 2002).
Neuropathogenesis of viral infections
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Avindra Nath, Joseph R. Berger
Cytotoxic immune responses play an important role in viral clearance from the brain. This may be established through several different mechanisms. Interactions of T-cell receptors with antigenic peptide bound to major histocompatibility complex (MHC) on the surface of antigen presenting cells (APCs) occurs in a protected environment called the immunological synapse. The immunological synapse contains at least two functional domains: A central cluster of engaged antigen receptors and a surrounding ring of adhesion molecules [35]. This is critical for the initiation of the cell-mediated immune responses. Thus, the lack of MHC antigen expression in neurons means that viruses that infect neurons may escape cytotoxic immune responses [36]. However, neurons may trigger the apoptotic pathways in an effort to eliminate the virus [37].
Active Specific Immunization by the Use of Leukemic Dendritic Cell Vaccines
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
Ilse Houtenbos, Gert J. Ossenkoppele, Arjan A. van de Loosdrecht
When T cells and APC encounter, a defined sequence of cellular and molecular interactions follow. After the initial scanning of the APC by filopodial projections of the T cell, antigen recognition by the TCR and development of TCR-derived signals, such as calcium influx, the T cell stops crawling (23). Interaction of T cells with APC results in the formation of a contact zone called the immunological synapse (IS) (24). Assembly of the IS occurs in several stages. MHC molecules interacting with TCR are first seen to accumulate in a ring surrounding a central cluster of adhesion molecules with LFA-1 and ICAM-1 interactions, forming the immature synapse. This synapse later inverts in a way that a central zone of TCR termed the central-supramolecular activating complex (c-SMAC) is surrounded by a peripheral ring of adhesion molecules (25). The function of this highly organized structure remains controversial. Initially, the synapse was thought to represent a structure necessary for initiating signals, but more recent data have demonstrated that calcium signaling, for example, already occurs before formation of the c-SMAC, when the IS is immature (26). Several other functions have been ascribed to the IS, such as directing secretion of cytokines, enhanced signaling and the balancing of enhancing, and terminating signals to maintain agonist-triggered signals in T cells (27).
F11R/JAM-A: why do platelets express a molecule which is also present in tight junctions?
Published in Platelets, 2023
Piotr Kamola, Anna Babinska, Tomasz Przygodzki
The involvement of platelets in the regulation of immunological processes is well known and was profoundly reviewed.71,72 Until today, there are no data regarding platelet F11R/JAM-A involvement in such regulation. There are however certain indications suggesting such a possibility. It has been recently shown that F11R/JAM-A present on dendritic cells is involved in regulation of T cells differentiation.73 The site of contact of these two types of cells where the interaction of the molecules crucial for the process occurs is called immunological synapse. This structure is known to contain LFA-174 which, as mentioned above, is the only known protein interacting with F11R/JAM-A other than F11R/JAM-A itself. Taking this into account, it could be assumed that platelet F11R/JAM-A may be involved in immunomodulatory processes.
Primary Immunodeficiency and Thrombocytopenia
Published in International Reviews of Immunology, 2022
Maryam Mohtashami, Azadehsadat Razavi, Hassan Abolhassani, Asghar Aghamohammadi, Reza Yazdani
In other T-cell defects, the congenital thrombocytopenia category has been reported and explained in detail in the following section. The Wiskott-Aldrich syndrome (WAS), which is traditionally known as X-linked thrombocytopenia is a syndromic CID characterized by a mutation in the WAS gene. Autoimmune diseases have increased in these patients because of the high percentage of self-reactive T- cell [90].. Another defect in these patients is related to impairment in polymerize and reorganize actin, as the development of immunological synapse does not form completely [91]. Also, mutations in the WAS gene influence platelets and these patients experience bleeding related to small platelet size and thrombocytopenia. It has been suggested that impaired platelets in WAS patients are due to cytoskeletal changes occurring in platelets circulation [92, 93].
Role of platelets and megakaryocytes in adaptive immunity
Published in Platelets, 2021
Genevieve Marcoux, Audrée Laroche, Jenifer Espinoza Romero, Eric Boilard
While most molecules were identified in the intracellular compartment, surface expression by platelets is necessary for the formation of immunological synapse with T cells. Confocal microscopy analysis revealed that MHC I, B2-MG, TAP1 and TAP2 could localize on the surface of thrombin-activated platelets, pointing to their secretion upon activation [63]. Moreover, young murine platelets displayed higher levels of MHC I molecules on their plasma membrane than older platelets, suggesting that MHC I surface expression is modulated throughout the platelet lifespan [65]. Platelet activation during infection can also lead to the expression of MHC I on the plasma membrane: both murine and human platelets increase expression of MHC I molecules in response to infection by Plasmodium berghei [64] and dengue virus [66].