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

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

ce an immune reaction and subsequently be toxic to other organ cells or their own tissue cells, if released to the systemic circulation. 89, 90 Matzniger proposed an interesting hypothesis for this basic immunological concept, the danger model. Herein, antigen presenting cells (APCs) can be activated by danger/alarm signals (initiators of inflammation) from the injured cells that are caused by pathogens, toxins, mechanical damage, and so forth. The intracellular contents from necrotically died cells could potentially be a danger signal when released, but not that of healthy cells or by cells undergoing physiological deaths (apoptosis). 89 Complete recovery from a systemic infectious disease may be defined as the state in which not only etiologic agents and inflammatory mediators from pathogens but also the substances produced during immune reactions including cytokines and the debris from the injured cells have been completely removed by immune cells, if those substances could be toxic to other tissue cells. We define these toxic proteins as "pathogenic proteins", classifying external pathogenic proteins as those which are of the pathogen origin and internal pathogenic proteins as those which are of host origin, including prions. A strict protein control system controls the balance of proteins and removes the pathogenic proteins at a molecular level in humans. Serum proteins including albumin, immunoglobulins and various hormones are maintained at constant levels in a steady (healthy) state by unknown protein control systems, and we have named these systems as "protein homeostasis systems". Here, we postulated that the immune system of the host is one of the protein homeostasis systems in vivo. The main function of immune cells at a molecular level is to control of a variety of proteins by recognition of size. Innate immune cells (neutrophils and phagocytic monocytes) control larger proteins (microbes and injured cells as a whole), B cells control proteins via antibody production, and T cells control small proteins which cannot induce antibod-corresponding immune cells, including macrophages and T cells, may also be involved in the pathogenesis of keloids. 96 T cells can be activated by various stimuli such as mitogens and monoclonal antibodies for various receptors on T cells in vitro, thus the mechanisms of T cells activation in vivo may be different in various pathologic conditions. Although helper T cells can be divided into functional subtypes such as Th1, Th2, Th17 and regulatory T (Treg) cells according to the cytokines produced from the T cells, it is expected that more T cells subtypes, which produce different cytokines, may exist in different pathogenic lesions in vivo. 97 Therefore, the functions of T cells are more diverse and complex than we have previously known.