Autoimmunity OPTM 2042 PDF

Summary

This presentation covers the topic of autoimmunity, including aspects like acute and chronic inflammation, mechanisms of immunological tolerance and pathogenesis. It also discusses various ocular autoimmune diseases, including their symptoms and how they affect the eye. The presentation offers a comprehensive overview of relevant medical concepts and their clinical implications for autoimmune diseases

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 This Ph oto by Unknown author is licensed und er CC BY. Autoimmunity  Acute inflammation ▪ Innate immune...

 This Ph oto by Unknown author is licensed und er CC BY. Autoimmunity  Acute inflammation ▪ Innate immune system usually controls or eliminates inflammatory stimulus This Ph oto by Unknown author is licensed und er CC BY-SA.  Chronic inflammation ▪ Failure of elimination of inflammatory stimulus ▪ Persisting microbes ▪ On-going accumulation of neutrophils, macrophages and activated T cells ▪ Local deposition of fibrous connective tissue, a granuloma, may form  Too vigorous or prolonged immune response may cause bystander tissue  damage Hypersensitivity response This Ph oto by Unknown author is licensed und er CC BY-SA-NC. TOLERANCE Immunological tolerance is a complex series  of mechanisms that impair the immune  system to mount responses against self antigens. 2006;1(3):187-96. doi: 10.1007/BF02934736. This Ph oto by Unknown author is licensed und er CC BY.   Failure of Tolerance Autoimmunity  ▪ Presence of immune responses against self- tissue ▪ Loss of self-tolerance ▪ May be harmless ▪ Low titre of autoantibodies Autoimmunity ▪ May cause significant organ damage ▪ Organ specific ▪ Myasthenia gravis ▪ Multi organ involvement ▪ Systemic lupus erythematosus  Polygenic and numerous susceptibility genes Predisposing contribute to AI factors Women > Men Certain human leukocyte antigens on T cells HLA B27 – Ankylosing spondylitis HLA DR2 - SLE Specific trigger? Infection Smoking Hormone levels e.g. pregnancy and SLE Drugs e.g. anti-TNF therapy and MS Environmental stimuli  ▪ Failure of immune tolerance ▪ The acceptance and recognition of self ▪ Failure of central tolerance ▪ Escape of “self-reactive” Pathophysiology lymphocytes ▪ Failure of peripheral tolerance ▪ Regulatory T cells fail to suppress “self-reactive” lymphocytes  Pathogenesis Molecular Mimicry Release of sequestered “hidden” antigens from damaged tissue Release of inflammatory cytokines that overwhelm local self-regulatory mechanisms  Pathophysiology ▪ Antibodies react with cell-surface antigens ▪ Graves disease ▪ Antibodies against the Thyroid Stimulating Hormone Receptor causes hyperthyroidism ▪ Myasthenia gravis ▪ Antibodies coat acetylcholine receptors preventing nerve signals from travelling to the muscles Pathophysiology  ▪ Immune complexes of antibodies and complement deposits ▪ Systemic lupus erythematosus ▪ Immune complexes deposits found in the kidney glomerular basement membrane ▪ Ocular manifestations ▪ Keratoconjunctivitis sicca, conjunctivitis, uveitis, episcleritis, scleritis, keratitis, retinal hemorrhages, retinal vasculitis, proliferative retinopathy, optic neuritis, ischemic optic neuropathy, hemianopia, amaurosis, internuclear ophthalmoplegia, pupillary abnormalities, oculomotor abnormalities, visual hallucinations https://www.aafp.org/afp/2002/0915/p991.html Pathophysiology  ▪ Immune complexes of antibodies and complement deposits ▪ Rheumatoid arthritis ▪ Immune complexes deposit in the joints. ▪ Rheumatoid factor (RF) is tested - found in ~10% healthy individuals ▪ Ocular manifestations ▪ Keratoconjunctivitis sicca, scleritis, episcleritis, keratitis, ulcerative keratitis, choroiditis, retinal vasculitis, episcleral nodules, retinal detachments, macular edema https://www.aafp.org/afp/2002/0915/p991.html  Pathophysiology ▪ Destruction by T cells ▪ Type 1 diabetes ▪ T cell destruction of pancreatic beta cells   THE EYE & AUTOIMMUNITY This Ph oto by Unknown author is licensed und er CC BY-NC-ND.  The eye and autoimmunity ▪ As sole organ ▪ As part of a multisystem disorder ▪ Connective tissue disorders ▪ Vasculitis ▪ Neurological  Ocular Autoimmune Diseases ▪ Keratoconjunctivitis sicca ▪ Dry eye syndrome ▪ keratoconjunctivitis associated with decreased tears ▪ Caused by lymphocytic infiltration and fibrosis of lacrimal glands ▪ Primarily CD4 along with B and plasma cells ▪ Lack of tears can lead to recurrent corneal erosion, keratitis and corneal opacification  Ocular Autoimmune Diseases ▪ Autoimmune Uveoretinitis ▪ An inflammatory autoimmune disease of the neural retina of the eye ▪ T cells (particularly Th1 cells) and monocytes ▪ Break through the blood-retina barrier ▪ Damage the photoreceptor cell layer of the retina ▪ Impaired vision or blindness ▪ Antibodies to retinal antigens also present ▪ Expression of HLA-DR3, -DR4, DQ6 or DQ8 have been found to be associated with it  Sympathetic ophthalmia ▪ Caused by prior trauma or intraocular surgery - perforating wound of the uvea followed by a similar severe reaction in the other eye that may lead to bilateral blindness ▪ Bilateral, granulomatous uveitis Ocular ▪ Exposure of immune privileged antigens Autoimmune leads to a bilateral immune response Diseases ▪ Primary inflammatory mediators: T cells (both CD4 and CD8+) ▪ Dalen-Fuchs nodules - Collections of epithelial cells lying between Bruch membrane and the retinal pigment epithelium - are seen in this disease

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