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Hyperactive immune resistance brings blindness in old age
July 25, 2008
Recent discoveries regarding the origins of senile blindness Age-dependent macular degeneration (AMD) is the commonest cause of blindness in the western industrialised nations. Hereditary changes in the regulation of the immune system influence the risk of contracting AMD. Opthalmologists at the University Clinic in Bonn, working in co-operation with researchers from Göttingen, Regensburg and Great Britain, have now, for the first time, demonstrated that in cases of senile blindness the patient's immune resistance is hyperactive throughout his entire body. An Anglo-German research team embracing immunologists from Göttingen University has added a further important aspect to our current knowledge of the processes leading to senile blindness. For the first time, they have been able to show that in the case of patients with AMD their entire immune system is hyperactive. It had not previously been known whether such an immune reaction affecting the entire body played any role in this eye disease. The investigation was conducted by scientists from Bonn, Göttingen, Regensburg and Oxford under the leadership of Privatdozent Dr. Hendrik Scholl of Bonn University's Eye Clinic. The results achieved by this research team have now been published in the current edition of the PLoS ONE: http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002593Faults in the (immune) System The Anglo-German research team worked on the hypothesis that one cause of the appearance of senile blindness, AMD, might be faulty regulation of the so-called complement system. This system is an important element in our hereditary immune resistance, and is involved where inflammatory reactions occur. Previously, it had only been known that changes in genes containing the hereditary information for proteins in the complement system increase the risk of contracting AMD. Some of these proteins activate, others inhibit, the complement system. The team examined the blood of a total of 112 AMD-patients and 67 healthy control persons for signs of faults in the regulation of their complement systems. They sought out changes in protein concentration which would indicate activation of the complement system. The experiments were conducted in Göttingen University's Department for Cellular and Molecular Immunology under the leadership of Professor Dr. Martin Oppermann. The investigations of the patients' blood did, indeed, reveal clear changes in the concentrations of a number of complement proteins which, moreover, correlated closely to the previously identified hereditary factors. Dormant inflammatory Situation of the Body "Our study has revealed for the first time that in the case of AMD patients the complement system is hyperactive over the entire body", Dr. Hendrik Scholl declares. The typical substances indicating a permanent inflammatory reaction circulate in the blood. "These results infer that senile blindness may arise from a permanent state of inflammation in the body. This can obviously lie dormant for decades, then in advanced old age can lead to the appearance of symptoms of the disease. According to Dr. Scholl, the point of most acute vision, at the centre of the retina, appears to be the susceptible point. In Germany, an estimated 4.5 million people suffer from age-dependent macular degeneration (AMD). With this disease, the point of most acute vision on the retina (macula) becomes subject to progressive deterioration. The patient can no longer read, and he or she loses the ability to lead an independent existence. Opthalmologists had hitherto known comparatively little about the causes of this disease, except that hereditary factors were involved, and also other easily influenced factors, such as smoking. University of Bonn

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The Complement System: Novel Roles in Health and Disease
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The Complement System: Novel Roles in Health and Disease surveys the advances in basic and applied research on the complement system over the past few years. Complement is a major protein network in blood that has been traditionally conceived as part of the immune system, a proinflammatory cascade engaged in nonspecific antimicrobial defence. However, it became clear recently that this system also plays an essential role in specific, adaptive immune responses, as well as in many basic physiological processes including cardiovascular regulation, pregnancy and tissue regeneration, just to mention a few. Complement proteins are widely involved in the immune evasion tactics of infectious microbes and cancer cells, and derangement of complement function contributes to numerous autoimmune,...
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The complement system plays a key role in host defense functions and inflammatory reactions. This book provides the present state-of-the-art of the theoretical fundamentals and basic biochemical features of the complement system, its activation and regulation. The biological functions are also discussed in the context of more complex conditions, e.g. host defense, chronic inflammation and graft rejection. This is a thorough revision of the 1988 edition, with additional chapters addressing the progress made in the understanding of the interconnection of the complement system and other mediator systems, especially with cellular receptors. The immunopathology section has been expanded, and a chapter on diagnostic procedures and their interpretation has been added.
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Current Topics in Complement (Advances in Experimental Medicine and Biology)
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The Third Aegean Conferences Workshop on Complement-Associated Diseases, Animal Models, and Therapeutics convened to discuss progress in complement research as it pertains to human disease pathogenesis and therapeutics. The rapid pace of research and new experimental approaches allow an integrated view of the in vivo biology of the complement system. This book collects writings on the functions of complement, pathophysiology, protein structures, design of complement inhibitors, and complement assays discussed at the conference.
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Structural Biology of the Complement System
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Of recent, the structure of the complement system has received considerable attention, including the publication of several three-dimensional structures of complement proteins. This has led to the need for an authoritative resource to provide a complete overview of the basics, as well as an explanation of the cutting-edge work being accomplished in this emerging science.
Structural Biology of the Complement System is devoted to the full exploration of structural aspects of the complement system, with special consideration of the links between molecular structure and function.
Containing the work of leading authorities across the disciplines of immunology and structural biology, the book serves both as an introductory volume for newcomers to the field and as a comprehensive...
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The understanding how complement relates to glomerular diseases has evolved considerably during the last years. Substantial evidence has accumulated that explain how a defective or deregulated complement system results in kidney diseases. The combination and close interaction of basic research with clinical medicine has demonstrated an important role of complement effector and regulatory proteins in pathological settings of the kidney. A large panel of distinct human kidney diseases such as hemolytic uremic syndrome (HUS), membrano proliferative glomerulonephritis (MPGN), systemic lupus erythematosus (SLE) and in ischemic reperfusions injury and transplantation are caused by defective complement control. Genetic analyses have identified mutations in complement regulators that are...
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The Complement System
by K. Rother (Author), G.O. Till (Editor)
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This authoritative, single-source reference provides comprehensive examinations of the complement system-offering recent findings in basic science on the structure, biology, physiology, and pathophysiology of complement proteins and the latest therapeutic approaches towards the control of complement-mediated diseases. Written by over 40 international experts from North America, Europe, and Asia, The Human Complement System in Health and Disease · describes the molecular architecture of the complement system · details the structure of complement genes · discusses gene organization as well as the topology and chemistry of ligand-binding sites and catalytic centers of complement proteins · analyzes complement organization and activation, including phylogeny and the newly discovered...
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A team of expert investigators and clinical researchers comprehensively review complement's basic biology, its role in disease, methods to measure its activity, and strategies for its inhibition in patients. Each chapter focuses on a specific area of basic and applied complement biology, spelling out the activation pathways and complement receptors. Informative animal models are discussed in detail, including the relative values of each model and the important interspecies differences that can distort the interpretation of preclinical studies. The emphasis throughout is on the pros and cons of the therapeutic use of recombinant complement inhibitors in specific diseases. Cutting-edge and innovative, Therapeutic Interventions in the Complement System highlights for today's researcher and...
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Immunobiology of the Complement System: An Introduction for Research and Clinical Medicine
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