Immune Synapses Between Lymphocytes and Target Cells in Autoimmune Thyroid Diseases

The immune synapse is the interface between an antigen-presenting cell and a lymphocyte [1-4] as well as the interface between different lymphocytes, Natural Killer cells, and target cells [5]. This intercellular connection serves as a focal point for exocytosis and endocytosis [6]. Numerous investigations have elucidated the structure of the immunological synapse. The synapse is composed of a central region: a central supramolecular activation complex SMAC [cSMAC], a T cell receptor (TCR) cluster and associated signaling proteins, and peripheral SMAC ( pSMAC) of a ring of tight adhesion between the reacting cells [7]. The separated space of SMAC is the place of exocytic and endocytic events in this site but the precise site of signaling is not known [8]. The early signaling process occurs in peripheral microclusters in the pSMAC and the cSMAC in T and B cell synapses [9-12]. CD4 T cells form long-lived synapses with APCs – the synapses live few hours. CD8 T cells form transient synapses, lasting only minutes, because the target cells are killed [13,14]. In this cytotoxic synapse, activated Src kinases were detected in the cSMAC [13]. The cSMACs play an important role not only in signaling but also in receptor recycling because endosomal compartments polarize to the point immediately beneath the cSMAC of the immunological synapse [15]. The endosome comes to lie underneath the cSMAC as polarization of the microtubule skeletons occurs during synapse formation. This polarization is antigen-dependent. The receptor activation leads to accumulation of actin across the synapse and formation of an outer ring around the synapse [16,17]. The cytotoxic reaction of lymphocytes CD8 is connected with release of specialized lysosomes containing the lytic pore-forming protein perforin, which enables gransymes to lead to rapid apoptosis of the target cell [17]; the centrosome in the lymphocytes is polarized right up to the plasma membrane containing the synapse cSMAC [18]. The lytic granules are delivered to a specialized secretory domain within the synapse by moving along the microtubules toward the centro‐