# Immunological Aspects of EBV and Oral Mucosa Interactions in Oral Lichen Planus
## 3 Currently Existing Pathogenesis of OLP  
The exact pathogenesis of OLP remains unclear, although it is currently understood to be a chronic inflammatory process mediated by T cells. This process is initiated by an antigen or antigens that transform basal keratinocytes, rendering them vulnerable to cytotoxic immune responses from cells [45]. It has been established that OLP involves both innate and adaptive immune mechanisms [46; 47]. The trigger factor can be an unknown endogenous or exogenous antigen. The first cells involved in antigen recognition are keratinocytes, which can perceive small molecular elements expressed by microorganisms known as pathogen-associated molecular patterns (PAMPs). Typical PAMPs are bacterial lipopolysaccharidesaccharides (LPS), endotoxins, and viral-derived nucleic acids, which are identified by pattern-recognition receptors (PRRs) [45; 48]. On the keratinocyte surface are located PRRs, to which belong toll-like receptors (TLRs), C-type lectin receptors, cytoplasmatic nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), and retinoic-acid-inducible gene I (RIG-I)-like receptors [49]. Keratinocytes have the capability to produce various pro-inflammatory cytokines and chemokines, such as interleukin (IL)-I, IL-6, IL-8, and tumor necrosis factor (TNF)-\(\alpha\)[50], which promote the recruitment of immune cells such as neutrophils and T lymphocytes to the infection site. PRRs are recognized as endogenous factors, which are substances that are released due to damage to cells or tissues and are named danger-associated molecular patterns (DAMPs) [51]. TLRs are also expressed on the membranes of leucocytes, macrophages, dendritic cells, natural killer cells, T cells, and B cells and located on intracellular vesicles. In the literature review of [PERSON] et al. [47], the authors focused on the interrelationship between toll-like receptors (TLRs) and OLP, with a focus on the molecular behavior of oral keratinocytes following the activation of TLR signals. Therefore, it can be assumed that if a foreign protein molecule acts as an antigen by reaching the physical barrier of the oral mucosa and coming into contact with oral keratinocytes, it will be recognized by TLRs and the immune cells will become activated. In the pathogenesis of OLP, both antigen-specific and non-specific mechanisms may be involved [52; 53]. In the case of an antigen-specific mechanism, an antigen-peptide-loaded MHC I complex, located on basal keratinocytes, activates antigen-specific cytotoxic CD8+ T cells (CTL) with the following apoptosis of antigen-specific keratinocytes. This process is accompanied by the release by activated CD8+ T cells of cytokines such as granzymes, perforins, tumor necrosis factor alpha (TNF-a), Fas ligand (FAS-L), INF-gamma, IL-1, and IL-17 from other cells. This all promotes further inflammation [52; 53]. The secretion of several pro-inflammatory cytokines activates epithelial Langerhans cells (LCs), also known as antigen-presenting cells (APCs), and the TLRs-dependent activation is required to induce dendritic cell maturation and migration to regional lymph nodes and naive T cell activation [54]. From APCs or an active T helper cell, requires co-stimulation on CD4+ T and CD8+ T cells located T cell receptor (TCR) complex activation. The TCR recognizes the antigen and the relevant antigen-presenting MHC complex [55]. The specific adaptive immune response is controlled by the T follicular helper (Tfh), cytotoxic T lymphocytes (CTLs), T cell subtypes Th1, Th2, T17, and regulatory T cell (Treg), which are distinguished by the types of cytokines they secrete [56]. According to [PERSON] et al. [56], TLRs are also involved in T cell development and give a signal to reprogram Treg cells into helper cells [56]. T cell subtypes Th1 and Th2 participate in the CD8+ T lymphocytes activation, thus helping the apoptosis of the keratinocytes [57]. Since all these processes activate TLRs, then through DAMPs or PAMPs, other keratinocytes may also be affected [58].