The Danger Model Approach to the Pathogenesis of the Rheumatic Diseases

Figure 1

Basic comparison of the postulates between the self-non-self- (SNS-) model and the danger model (DM). In the SNS-mode, the triggering stimulus is the antigen which is by definition foreign, or, if endogenous, it is mistaken as foreign; once the antigen specific cells have been primed, the persistence of the immune response depends on the perpetual presence of an antigen and for the case of an autoantigen on its expression where it can be detected and processed by antigen presenting cells to T-cells; the severity of the immune reactions depends on the nature and amount of the antigen and the type of immune response it settles on. In the case of the DM the initial step is a scenario of disturbance within the tissues which can be explained by both biological or physical aggressions, the disturbed tissular cell signals to the local antigen presenting cells, and, as the aggression becomes more chronic the tissular cell communicates directly to T- or B-cells; the perpetuating cycle for the case of chronic autoimmune diseases relies on the repeated disturbance of the tissular cells by the annoying stimuli and self-proteins are recognized eventually as antigens due to the enhanced antigenic presentation costimulation upregulated by the soluble factors released by the stressed tissular cells. The severity of the immune reaction depends on the intensity and frequency of the disturbance that the stimuli infringe in the tissular cells.