"Research is to see what everybody else has seen, and to think what nobody else has thought." — Albert Szentgyorgyi
Autoimmunity: Methods and Protocols is intended to serve as a ready-to-use guide to establish and interrogate human and animal models of autoimmune diseases. The first chapter, "Pathogenesis and Spectrum of Autoimmunity," discusses major hypotheses driving this most tantalizing area of research since Paul Ehrlich proposed the concept of autoimmunity in 1900. Considering the great diversity and ever-changing spectrum of autoimmunity, it has not been possible to include models and experimental protocols for each known disorder. Rather, several chapters have been devoted to the most prevalent and complex diseases, such as rheumatoid arthritis, systemic lupus erythematosus, insulin-dependent diabetes mellitus, and multiple sclerosis. The chapters are contributed by laboratories actively using the models presented. Each chapter contains an introductory section that discusses the relevance of the model for a particular disease and for autoimmunity in general.
Part I contains methods and protocols to assess immunological and biochemical pathways relevant for disease pathogenesis. Chapters in this section focus on methods to identify susceptibility genes, intercellular signaling via cytokines, intracellular signaling through the T-cell receptor and signal processing via protein kinases, identification and enumeration of autoantigen-specific T cells and autoantibodies, and the dysregulation of apoptosis and its role in modification of self-antigens. Part II contains protocols to establish and assess inflammatory arthritis, systemic lupus erythematosus, myocarditis, thyroiditis, experimental autoimmune encephalo-myelitis, insulin-dependent diabetes mellitus, scleroderma, uveitis, and vitiligo. The methods center on the assessment of genetic, immunological, and biochemical parameters underlying spontaneous or exogenous antigen-induced diseases. Although the individual protocols focus on a specific disease, they can be adapted to investigate additional signaling pathways or pathogenic autoantigens.
Autoimmunity: Methods and Protocols should supplement those laboratory manuals that contain recipes for standard cell and molecular biology and immunology techniques, such as cell culture, gene cloning, sequencing, and amplification by polymerase chain reaction, vector design for the generation of transgenic and knockout animals, flow cytometry, fluorescence microscopy, electrophoresis, and gene and protein microarray methods.
Although these general methods are not described in detail here, they are appropriately referenced in each section.
I am grateful to Professor John Walker for his invitation and help with organizing and formatting this book and to Dr. Paul Phillips for his continued encouragement and support. With both my colleagues in the field and newcomers in mind, step-by-step protocols and detailed troubleshooting guides supplement all chapters. I am grateful to the distinguished authors for the time, expertise, and devotion that made this book possible.
If the reader feels that a particularly relevant disease or model is missing, I should be held responsible. Refining and extracting new meaning from old models and developing new ones is a constantly ongoing process. Therefore, our readers are invited to approach the authors with questions and comments or offer new models and protocols for a future edition.
Andras Perl, md, PhD
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