# Immunological Aspects of EBV and Oral Mucosa Interactions in Oral Lichen Planus
## 8 Possible Autoimmune Pathway in Oral Lichen Planus
Expression of viral or self-antigens and facilitation of the development of autoreactive B and T cells as well as proliferation are facilitated due to the high expression of human leukocyte antigens (HLA) on type III latency cells and APCs function [133]. The process is reinforced by III-latency cell-mediated cytokine production. However, [PERSON] [124] notes that it is obvious that the onset of a particular autoimmune disorder is not determined by one unified EBV action model. Figure 1 demonstrates the hypothetical pathway of EBV infection in the pathogenesis of OLP:  
1. After primary infection, infected B cells migrate through the bloodstream to the regional lymph nodes, where they stimulate the activation of CD8+ and CD4+ cells. As a result of the activation of CD4+ cells, B cells become active, which in turn become plasma cells. The lytic cycle is switched on by releasing a large number of EBV particles, which are able to directly infect oral epithelial cells. The spread of the newly produced virions to other cells and intercellular communication are probably provided by exosomes and microvesicles present in tissues and saliva;
2. Under certain conditions of the oral microenvironment and simultaneously with virus reactivation, the virus or virus-derived peptides present in saliva can be detected with the help of toll-like receptors (TLRs) and major histocompatibility complex I (MHC I) located on parakeartinized epithelium. If _str. spinosum_ superficial cell layers become infected, then the information, possibly also with the help of exosomes and microvesicles, is transferred to LCs belonging to antigen-presenting cells (APCs) and containing TLRs as well as major histocompatibility complex II (MHC II);
3. Activation of TLRs causes LC maturation and migration to the regional lymph node, with subsequent interaction with T and B cells and the release of antigen-specific T cell clones. The release of cytokines and chemokines under the epithelial basal membrane begins;
4. If the basal keratinocyte becomes infected, the viral epitope peptide binds to the extracellular portion of the MHC class I molecule, presented to antigen-specific cytotoxic CD8+ T cells, with the following apoptosis of the antigen-specific keratinocyte. This process is accompanied by the abundant release of cytokines and chemokines;
5. The proinflammatory status activates and then degrades mast cells. Chymase, the product of mast cells, damages the epithelial basement membrane through direct or indirect activation of T cells secreting and activating matrix metalloproteinase 9. This opens the way for CD8+ T lymphocytes to enter the epithelium. LCs can perceive epithelial antigens from apoptotic cells;
6. EBV is able to latently infect LC precursors in the circulation during their migration from the blood to the epithelium, where they differentiate into oral LCs. Infected LCs can present antigen to CD4+ T ly and CD8+ T ly and trigger an immunological response. Functionally altered LC functions can take over neighboring cells through the cross presentation of antigen;
7. Intensely damaged tissue can produce self-antigens that are recognized by LCs while activating autoreactive T cells. Enhanced development and formation of autoreactive B and T cells deepen tissue destruction, promoting the formation of autoimmune processes.