Immune tolerance and mechanisms of autoimmunity
Central and peripheral tolerance (AIRE, negative selection, anergy, Tregs, CTLA-4, PD-1, Fas), the monogenic diseases that prove each step, how genes and environment break tolerance, checkpoint inhibitor toxicity, and how to interpret autoantibodies.
Tier 1Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- Tolerance is the failure to respond to self. It is set in two places: central (thymus and marrow) and peripheral (tissues and lymph nodes).
- Autoimmunity happens when a genetically susceptible person meets an environmental trigger and tolerance fails at one or more checkpoints.
- Each checkpoint has a monogenic disease that proves its job: AIRE (APS-1), FOXP3 (IPEX), FAS (ALPS), CTLA-4 haploinsufficiency, C1q deficiency.
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Sources
- Abbas: Cellular and Molecular Immunology (10th ed.)Elsevier (Abbas, Lichtman and Pillai), 2022
- Janeway's Immunobiology (10th ed.)W. W. Norton (Murphy and Weaver), 2022
- Development of autoantibodies before the clinical onset of systemic lupus erythematosusNew England Journal of Medicine (Arbuckle et al), 2003
- Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosisScience (Bjornevik et al), 2022
- Dominant mutations in the autoimmune regulator AIRE are associated with common organ-specific autoimmune diseasesImmunity (Oftedal et al), 42:1185-96, 2015
- Range of antinuclear antibodies in 'healthy' individualsArthritis and Rheumatism (Tan et al), 1997
- Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline updateJournal of Clinical Oncology (Schneider et al), 2021
- eviQ: immune-related adverse eventsAU/NZCancer Institute NSW
- Australasian Society of Clinical Immunology and Allergy (ASCIA) information on autoimmune disease and antinuclear antibody testingAU/NZASCIA
- Last updated
- 14 November 2026
What changed
- 14 November 2026 Personal emails, About story and Australian-style copy