The first step in the immune pathogenic cascade of psoriasis is the capture and processing of auto-antigen by Langerhans cells or dendritic cells ("antigen-presenting cells" [APCs]) in the epidermis or dermis, respectively. The nature of the antigen is still unknown. There is, however, some evidence that in genetically predispo sed subjects, keratinocyte-derived peptides may be involved.
The APC-antigen complex migrates to a skin-draining lymph node, where the antigen is presented via major histocompatibility complex II (MHC II) on the surface of the APC to the T-cell receptor (TCR) of the specific naive CD4+ cell, or via MHCI to the TCR of CD8+ T cells respectively. Interaction of the APC-MHC-II/antigen-TCR complex is, however, not sufficient for T-cell activation.
The initial binding of T cells and APCs, as well as stabilization of the cell pair, is mediated by LFA-1 on T cell and ICAM-1 on the APC. This stabilized structure has been referred to as the "immunological synapse" (Fig. 5.1a), formation of which is followed by delivery of the antigen-specific signal (signal 1) and a costimu-latory signal (signal 2), which are also mediated by LFA-1 and ICAM-1. Delivery of signal 1 and signal 2 is followed by binding of cytokines that induce T cells to proliferate (i.e. undergo clonal expansion) and differentiate. Proliferation is thought to be largely mediated by the cytokine interleukin-2 (IL-2).
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Do You Suffer From the Itching and Scaling of Psoriasis? Or the Chronic Agony of Psoriatic Arthritis? If so you are not ALONE! A whopping three percent of the world’s populations suffer from either condition! An incredible 56 million working hours are lost every year by psoriasis sufferers according to the National Psoriasis Foundation.