Tolerance and autoimmunity

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Ian R Mackay, honorary professorial fellow (ian.mackay@med.monash.edu.au)

Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3168, Australia

Immune tolerance and autoimmunity are important clinically. Firstly, there are at least 40 known or suspected autoimmune diseases, and many are common (see box). Overall, 1 person in 31 is affected.1 Moreover, autoimmune type 1 diabetes is the most common of all chronic diseases of children. Secondly, autoimmune disease is poorly diagnosed because the onset can be stealthy, and initial symptoms are often non-specific—tiredness, fatigue, or fever. Thirdly, patients with autoimmune disease will expect an interpretation of their illness from their doctor. Fourthly, new insights are set to revolutionise management, by replacement of blanket immunosuppression with new selective immunotherapies

Prevalence of autoimmune diseases

Thyroid diseases (includes Hashimoto's thyroiditis and Graves' disease): >3% of adult women
Rheumatoid arthritis: 1% of general population, but female excess
Primary Sjögren's syndrome: 0.6-3% of adult women
Systemic lupus erythematosus: 0.12% of general population, but female excess
Multiple sclerosis: 0.1% of general population, but female excess
Type 1 diabetes: 0.1% of children
Primary biliary cirrhosis: 0.05-0.1% of middle aged and elderly women
Myasthenia gravis: 0.01% of general population, but female excess

Immune tolerance and the immune response

Figure 1 illustrates how tolerance is established and maintained and how it fails with ensuing autoimmunity. Specific immune and autoimmune responses involve the same elements. These include (a) an antigen (or autoantigen); (b) a response by interacting families and subsets of cells that include antigen presenting cells, T lymphocytes, and B lymphocytes; (c) messenger molecules, cytokines, chemokines, and their receptors; and (d) signalling and costimulatory molecules on cell surfaces (fig 2). Many of the functionally important cell surface molecules and their receptors are described by the cluster of differentiation (CD) nomenclature, based on their identification by characterised monoclonal antibodies.