Kawasaki Disease: Laboratory Findings and an Immunopathogenesis on the Premise of a ""Protein Homeostasis System

Lee, Kyung-Yil; Rhim, Jung-Woo; Kang, Jin-Han

At this point, we can deduce that the immunopathogene-ies, via cytokine production, using T cell receptors (TCR) or via their effect on cell-bound proteins. Macrophages may play the most crucial role in the immune/repair system of the host. Also, they synchronize the communications between innate immune cells and adaptive immune cells in inflammatory reactions, and between immune cells and regenerating tissue cells in repair reactions, via a complex of cytokine (protein) networks. Although the immune system of the mammals have been divided into the separate categories of innate immune system and adaptive immune system, the two immune systems work together against any internal or external insults in vivo. It is now accepted that the mediators (proteins) from innate immune reactions affect adaptive immune reactions. 91, 92 In infections of various pathogens, pathogen recognition receptors including Toll-like receptors (TLRs) and intracellular sensors which recognize components of pathogens (pathogen-associated molecular pattern) of infected cells and macrophages, induce the production of anti-agent proteins (in case of viruses and interferons) and other proteins including pro-inflammatory cytokines. These proteins may affect the function of adaptive immune reactions such as control of expression of co-stimulatory receptors or activation of specific immune cells. 91, 92 B cells (plasma cells) can produce antibodies for any proteins which are recognized by B cell receptors (BCRs). Theoretically, gene recombination of BCR genes can match all internal or external proteins. However, B cells cannot induce antibodies against small foreign proteins and a majority of self serum proteins. Similarly, TCRs of T cells also comprise recombination of variable TCR genes, matching nearly all peptides (proteins) that are constructed with 12-27 amino acids. Despite the more crucial role of T cells than B cells on host defense against invading pathogens (T cell deficiency is more severe compared to B cell deficiency), the role of TCRs is nearly unevaluated except for antigen presentation between T cells and APCs compared to B cell function. Lots of small peptides may exist in inflammatory lesions; however, the metabolism and role of these proteins remain to be evaluated. Indeed, small peptide hormones such as gonadotrophin releasing hormone (GnRH, decapeptide), vasopressin (9 peptide) and oxytocin (9 peptide) exist in vivo, and they have crucial roles on systemic hormonal homeostasis. 93 Furthermore in the nucleus of the cells, replication of DNA for cell proliferation and small microsomal RNAs, which regulate gene expression, may also be controlled by proteins, including DNA polymerases and nucleases, suggesting complex mechanisms of protein homeostasis at a cell level. 94 struggled with external insults in nature. The compositions of various pathogens and animal toxins, such as snake venom and insect venom are mainly proteins of various sizes, shapes and lethal doses. These toxic proteins may have their own affinity to different organ-tissue cells and bind to the receptors on the cells of the host. This toxic protein-receptor binding may induce direct cell injury and/or may produce new proteins through signal transduction pathways in the affected cells. The substances (proteins) from injured cells can be released to systemic circulation and signal other immune cells. Now, it is believed that substances from injured cells of a specific organ tissue can indu