The immune system has been known to be capable of distinguishing self from non-self since the pioneering work of Paul Erhlich more than a century ago. Originally described in experiments studying blood transfusion comp- ibility, the principle of “horror autotoxicus” is still valid, although today the phenomenon is usually described in terms of tolerance or ignorance. A great deal has been learned about the various processes preventing self-reactivity normally. These include processes that operate during immune cell ontogeny and subsequently on reactivity of mature lymphocytes in the periphery. They encompass mechanisms that are intrinsic to potentially reactive lymphocytes and can result in central or peripheral deletion or the alteration of functional potential. In addition, there are in?uences that are extrinsic to potentially auto-reactive lymphocytes, including the function of regulatory cells, d- ferentiation state of antigen-presenting cells, availability of self-antigen, the cytokine and chemokine milieu, as well as the traf?cking patterns involved in generating productive immune interactions. It is clear that the immune system devotes a considerable effort to the avoidance of the development of potentially pathogenic self-reactivity. Despite this, the development of self-reactivity is relatively common. - though the development of autoimmune disease is less frequent, autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, systemic lupus e- thematosus, psoriasis, thyroiditis, and myasthenia gravis, are all too common, and can cause considerable morbidity and even mortality.
Table of ContentsThe pitfalls of tolerance.- Fritz Melchers and Antonius Rolink: B cell tolerance – how to make it and how to break it.- Hartmut Wekerle: Breaking ignorance – the case of the brain.- Shimon Sakaguchi, Ruka Setoguchi, Haruhiko Yagi, and Takashi Nomura: Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in self-tolerance and autoimmune disease.- Innate and autoimmunity.- Joel F.G. Cohen-Solal, Venkatesh Jeganathan, Christine M. Grimaldi, Elena Peeva and Betty Diamond: Sex hormones and SLE: influencing the fate of autoreactive B cells.- The link between infection and autommunity.- Mike Recher and Karl S. Lang: Innate (over)immunity and adaptive autoimmune disease.- D.J.B. Marks, Nicholas Avrion Mitchison, A.W. Segal, Jochen Sieper: Can unresolved infection precipitate autoimmune disease?.- Sustaining chronic inflammation.- Udo S. Gaipl, Ahmed Sheriff, Sandra Franz, Luis E. Munoz, Reinhard E. Voll, Joachim R. Kalden, and Martin Herrmann: Inefficient clearance of dying cells and autoreactivity.- Alla Skapenko, Peter E. Lipsky, and Hendrik Schulze-Koops: T cell activation as starter and motor of rheumatic inflammation.- Fionula Mary Brennan, Andrew David Foey and Marc Feldmann: The importance of T cell interactions with macrophages in rheumatoid cytokine production.- Thomas Dörner and Peter E Lipsky: Signalling pathways in B cells: Implications for autoimmunity.- Rudolf A. Manz, Katrin Moser, Gerd-Rüdiger Burmester, Andreas Radbruch, and Falk Hiepe: Immunological memory stabilizing autoreactivity.- Genetics and genes.- Martina Johannesson, Malin Hultqvist, Rikard Holmdahl: Genetics of autoimmune diseases – a multistep process.- Susannah Brydges and Daniel Kastner: the systemic autoinflammatory diseases: inborn errors of the innate immune system .- Subject Index