cell wall arthritis. unit 15.4 describes protocols for induction of adjuvant arthritis in the rat. It should be noted that, in contrast to many of the other protocols in the chapter, adjuvant arthritis is induced by oil-in-water emulsions that contain M. tuberculosis but do not contain tissue-specific antigens. In certain rat strains, disease can even be induced by certain oils in the absence of mycobacteria. Antibodies play no role in the pathogenesis of this disease, and it can be regarded as a model of purely T cell-mediated joint inflammation and destruction. The nature of the autoantigen recognized by the disease-initiating T cells in this model is completely unknown, although it has been proposed that the T cells may recognize mycobacterial or cartilage proteoglycans or mycobacterial or mammalian heat shock proteins. unit 15.5 describes protocols for the induction and assessment of collagen-induced arthritis (CIA) in both the rat and the mouse. Following immunization with heterologous collagen, animals develop a polyarthritis that in many respects resembles rheumatoid arthritis in humans. In contrast to adjuvant arthritis, both cellular and humoral immune responses have been shown to play important roles in the pathogenesis of CIA. unit 15.5 also contains detailed protocols for the preparation and purification of native type II collagen from chicken tissues, as commercial sources of this critical reagent are scarce. unit 15.10 describes another animal model for arthritis in rats, which uses peptodoglycan-polysaccharide polymers (PG-PS) derived from the cell walls of Streptococcus pyogenes. This model induces inflammatory responses with many of the features that characterize human rheumatoid arthritis. In addition to arthritis, injection of PG-PS can also induce hepatic, splenic, and peritoneal granulomas. Such responses are considered representative of several naturally occurring inflammatory disorders. unit 15.6 contains protocols for the induction of experimental autoimmune uveitis (EAU) in rodent model systems. This autoimmune disease in animals represents an excellent model for autoimmune inflammatory diseases of the posterior uvea in humans. Table 15.6.2 lists in detail the retinal antigens and peptides derived from them that can be used to induce EAU in Lewis rats. In the mouse, EAU can only readily be induced by immunization with peptide 161 to 180 of human interphotoreceptor retinoid-binding protein. Similarly, induction of experimental autoimmune thyroiditis (EAT), an excellent model for autoimmune (Hashimoto's) thyroiditis in humans, by immunization with mouse thyroglobin, is presented in unit 15.7.
Mouse and rat models for human myasthenia gravis, a T cell-dependent, antibody-mediated autoimmune disease, are presented in unit 15.8. This unit includes protocols for extraction and purification of Torpedo californica electric organ acetylcholine receptors (AChR), which are used as the immunogen to induce disease. In addition, detailed protocols for measuring anti-AChR antibody, clinical disease progression, and the effects of acetylcholinesterase inhibitors to reverse the disease are described.
unit 15.11 presents methods for inducing a form of immune complex glomerulonephritis known as IgA nephropathy in mice and rats. This disease is distinguished from other forms of immune-complex glomerulonephritis by virtue of the predominance of IgA as the major class of Ig within the aggregates. Protocols describe the induction of IgA nephropathy using one of several inciting antigens including inert proteins (e.g., ovalbumin) and Sendai virus. Methods used to evaluate disease are also presented.
unit 15.13 describes an adoptive transfer approach for inducing inflammatory bowel disease (IBD) in SCID mice. Reconstitution of such mice with CD45RBhigh CD4+ cells from BALB/c mice results in IBD with many of the gastrointestinal lesions and histological features present in human disease.
Was this article helpful?