Diseases that tend to occur in clusters are grouped in single boxes. Clustering is defined as more than one disease affecting a single patient or different members of a family. Not all autoimmune diseases can be classified according to this scheme. For example, autoimmune hemolytic anemia can occur in isolation or in association with systemic lupus erythematosus.
as a solitary entity and could be classified as an organ-specific disease. In other circumstances it can occur in conjunction with SLE as part of a systemic autoimmune disease.
A prevalent variant of chronic inflammatory disease is inflammatory bowel disease (IBD), which includes two main clinical entities—Crohn’s disease (discussed later in this chapter) and ulcerative colitis. We discuss IBD in this chapter because it has many features of an autoimmune disease, even though it is not primarily targeted against self-tissue antigens. Instead, the targets of the dysregulated immune response in IBD are antigens derived from the commensal microbiota resident in the intestines. Strictly speaking, therefore, IBD is an outlier among autoimmune diseases in that the immune response is not directed against ‘self’ antigens; rather, it is directed against microbial antigens of the resident, or ‘self,’ microbiota. Nevertheless, features of immune tolerance breakdown are also seen in IBD, and, as with the organ-specific autoimmune diseases, the tissue destruction wrought by the aberrant immune response is primarily localized to a single organ—the intestines.
15-10 Multiple components of the immune system are typically recruited in autoimmune disease.
Immunologists have long been concerned with which parts of the immune system are important in different autoimmune syndromes, because this can be useful in understanding disease etiology and developing therapies. In myasthenia gravis, for example, autoantibodies produced against the acetylcholine receptor block receptor function at the neuromuscular junction, resulting in a syndrome of muscle weakness. In other autoimmune conditions, antibodies in the form of immune complexes are deposited in tissues and cause tissue damage as a consequence of the inflammation that results from complement activation and ligation of Fc receptors on inflammatory cells.
Relatively common autoimmune diseases in which effector T cells seem to be the main destructive agents include type 1 diabetes, psoriasis, IBD, and multiple sclerosis. In these diseases, T cells recognize self peptides or peptides derived from the commensal microbiota that are complexed with self MHC molecules. The damage in such diseases is caused by T cells recruiting and activating myeloid cells of the innate immune system to cause local inflammation, or by direct T-cell damage to tissue cells.
When disease can be transferred from a diseased individual to a healthy one by transferring autoantibodies and/or self-reactive T cells, this both confirms that the disease is autoimmune in nature and also proves the involvement of the transferred material in the pathological process. In myasthenia gravis, serum from affected patients can transfer symptoms to animal recipients, thus proving the pathogenic role of the anti-acetylcholine autoantibodies (Fig. 15.11). Similarly, in the animal model disease EAE, T cells from affected animals can transfer disease to normal animals (Fig. 15.12).