In this review, we follow the notion that autoimmune disease can have causes other than “stochastic mistakes of adaptive immunity”. The therapeutic ramifications of these two views are also distinct: a T or B cell-centric view calls for immunosuppressive or tolerizing approaches, while the concept of specific biological processes resulting in autoimmunity will look for specific modulation of such processes without the need for suppressing the normal function of the immune system. The two concepts are of course not mutually exclusive, but they shape our thinking in different ways: while the former focuses autoimmunity research on T or B cell antigen receptor repertoire and mechanisms of central and peripheral tolerance, the notion that autoimmunity may arise from specific biological processes broadens the search for disease triggers and attempts to understand the escalation towards disease. Rather, it seems that autoimmune diseases must be the result of distinct and unique pathophysiological processes that evolve over an extended period of time into a specific disease. This pattern of many distinct diseases does not readily mesh with the commonly accepted notion that autoimmunity starts with a simple stochastic loss-of-tolerance blunder by a T cell. Nevertheless, patients that deviate radically from the typical disease profiles are rare.
#Midas gen 2015 with medicine 4shared series
Granted, there is variability and heterogeneity within most such disease entities and some diagnoses may in fact represent more than one distinct disease or a series of mechanistically different molecular “endotypes” of the disease.
#Midas gen 2015 with medicine 4shared full
diagnoses), rather than spanning the full spectrum of autoimmunity against random antigens. Relevant Molecular Concepts of Human Autoimmune DiseasesĪn important feature of clinical autoimmunity is that patients tend to fall into a discrete number of reasonably well delineated and named disease entities (i.e. Here, we discuss the evidence and the proposed mechanisms, and assess the therapeutic options that emerge from the current understanding of this field. Hence, if not properly controlled, they may drive a frustrated and escalating chronic, or episodic, immune response to the point of a frank autoimmune disorder. Importantly, these endogenous proviruses cannot be eliminated by the immune system the way it can eliminate exogenous viruses. Many of these loci still encode for retroviral proteins that have retained some, or all, of their original functions. Here, we discuss a different, but perhaps mechanistically related possibility, namely that retrotransposons or retroviruses that infected us in the past and left a lasting copy of themselves in our genome still can provoke an escalating immune response that leads to autoimmune disease. However, no specific virus has yet been established as being truly causative. Viruses have topped the lists of suspects for decades, and it seems that many viruses, including those of the Herpesviridae family, indeed can influence disease initiation and/or promote exacerbations by a number of mechanisms that include prolonged anti-viral immunity, immune subverting factors, and mechanisms, and perhaps “molecular mimicry”. Numerous potential triggers of autoimmunity have been proposed over the years, but very few of them have been conclusively confirmed or firmly refuted. The molecular events that lead to these diseases are still incompletely understood and their causes remain largely unknown. More than 200 human disorders include various manifestations of autoimmunity.
0 kommentar(er)
