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AUTOIMMUNITY

AUTOIMMUNITY. II MBBS Dr Ekta Chourasia Microbiology, GMCA. AUTOIMMUNITY. A condition in which structural or functional damage is produced by the action of immunologically competent cells or Abs against the normal components of the body. Features Of Autoimmune Diseases.

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AUTOIMMUNITY

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  1. AUTOIMMUNITY II MBBS Dr Ekta Chourasia Microbiology, GMCA

  2. AUTOIMMUNITY • A condition in which structural or functional damage is produced by the action of • immunologically competent cells or • Abs against the normal components of the body. Dr Ekta, Microbiology

  3. Features Of Autoimmune Diseases • An elevated level of Igs. • Deposition of Igs or their derivatives at particular sites like glomeruli. • Accumulation of lymphocytes & plasma cells at the site of lesion. • Benefit from corticosteroidor other immunosuppressive therapy. • Genetic predisposition. Dr Ekta, Microbiology

  4. Features Of Autoimmune Diseases • Occurrence of more than one type of autoimmune disorders in an individual. • Higher incidence among females. • Usually non-reversible (chronic) Predisposing factors • Familiar history. • Certain HLA haplotypes - Rheumatoid Arthritis - HLA DR4 Dr Ekta, Microbiology

  5. Mechanisms Of Autoimmunisation • Molecular mimicry - Cross reacting foreign Ags • Polyclonal B cell activation • Breakdown of immunological homeostasis (tolerance) • Sequestered Ags Dr Ekta, Microbiology

  6. 1 .Molecular Mimicry • Due to the presence of cross reacting Ags - Presence of epitopes withidentical peptidesequences in some infecting micro-organisms & self Ags. e.g * Following Anti-Rabies immunisation in humans with the neural vaccine of infected sheep brain - due to the presence of organ specific Ags. * Following streptococcal infection – Streptococcal M proteins and the heart muscle. Dr Ekta, Microbiology

  7. Dr Ekta, Microbiology

  8. 2. Polyclonal B-cell Activation • Non-specific activation of multiple B cellclones by certain stimuli like * Chemicals - 2-mercaptoethanol * Bacterial products - PPD, LPS * Enzymes - trypsin * Antibiotics - nystatin * Micro-organisms - Mycoplasma, EBV, malaria • Multiple non-specific Abs are formed during such conditions. Dr Ekta, Microbiology

  9. 3. Breakdown Of Immunological Homeostasis • Cessation of tolerance to self Ag. • Enhanced helper T-cell and decreased suppressor T-cell functions Dr Ekta, Microbiology

  10. tolerance to self Ag. Dr Ekta, Microbiology

  11. 4. Release of Sequestered Ags • Sequestered Ags - Certain Ags are present in closed systems (compartments) and are not accessible to the immune apparatus. e.g * Lens protein of the eye is enclosed in its capsule & does not circulate. * Sperm Ags - spermatozoa develop at puberty; no tolerance during fetal life. Dr Ekta, Microbiology

  12. Classification Of Autoimmune Diseases • Based on the site of involvement and nature of lesions, autoimmune diseases can be classified as * Haemocytolytic * Localised (or organ-specific) * Systemic (or non-organ specific) * Transitory diseases Dr Ekta, Microbiology

  13. Dr Ekta, Microbiology

  14. Hemolytic Autoimmune Diseases • AUTOIMMUNE HAEMOLYTIC ANAEMIAS * Antibodies against RBCs. * 2 groups – cold & warm autoantibodies Cold autoAbs : - complete Abs, IgM class - agglutinate RBCs at 4C, not at 37C - seen in atypical pneumonia, trypanosomiasis, black water fever. Dr Ekta, Microbiology

  15. Warm autoAbs: - incomplete Abs, IgG class - detected by direct Coombs test (coat RBCs) - seen in pts. taking drugs like sulphonamides, antibiotics, alpha methyl dopa etc *such RBCs coated with Abs are prematurely destroyed in the spleen & liver. Dr Ekta, Microbiology

  16. Hemolytic Autoimmune Diseases 2. AUTOIMMUNE THROMBOCYTOPENIA * Auto-Abs against platelets : idiopathic thrombocytopenic purpura 3. AUTOIMMUNE LEUCOPENIA * Anti-leucocyte Abs seen in the serum of patients with SLE & RA. Dr Ekta, Microbiology

  17. Localised Autoimmune Diseases • Insulin dependent DM – autoimmunity against islets of Langerhans in Pancreas. • AUTOIMMUNE DISEASES OF THE THYROID GLAND A. Hashimoto’s thyroiditis. Dr Ekta, Microbiology

  18. Localised Autoimmune Diseases • AUTOIMMUNE DISEASES OF THE THYROID GLAND B. Thyrotoxicosis (Grave’s disease) - Abs against thyroglobulin Dr Ekta, Microbiology

  19. Localised Autoimmune Diseases • ADDISONS’S DISEASE * antibodies to the cells of Zona Glomerulosa layer of adrenal glands Dr Ekta, Microbiology

  20. Localised Autoimmune Diseases • MYASTHENIA GRAVIS * Abs against ACh receptor on myoneural junctions of striated muscle – prevents binding of Ach to its receptor – impaired muscle contraction. * seen in infants born to myasthenic mother but recovery takes place by 2 months of age Dr Ekta, Microbiology

  21. Localised Autoimmune Diseases • PERNICIOUS ANAEMIA 2 types of auto-antibodies are present - * against the parietal cells of the gastric mucosa - Atrophic gastritis, Achlorhydria. * Ab against the intrinsic factor – prevents Vit.B12 absorption. Dr Ekta, Microbiology

  22. Dr Ekta, Microbiology

  23. Localised Autoimmune Diseases • AUTOIMMUNE DISEASES OF THE EYE 1. Phacoanaphylaxis * Autoimmune response to the lens protein following cataract surgery 2. Sympathetic Ophthalmia in opposite eye following perforating injuries of the eye, involving ciliary body & iris. Dr Ekta, Microbiology

  24. Localised Autoimmune Diseases • AUTOIMMUNE DISEASES OF THE SKIN * Pemphigus vulgaris – blistering disease of the skin - Abs to desmosomes, results in breakdown of epithelial cells • AUTOIMMUNE ORCHITIS * Lymphocytic infiltration of testes and circulating Abs to the sperms & germinal cells * Follows mumps orchitis Dr Ekta, Microbiology

  25. Systemic Autoimmune Diseases • Immune response to a variety of self-Ags • Damage to several organs & tissuesystems. • Includes – SLE (systemic lupus erythematosus) RA (rheumatoid arthritis) Polyarteritis nodosa Sjogren’s syndrome Dr Ekta, Microbiology

  26. SLE • Chronic , multisystem disease • Auto-antibodies against cell nuclei, intra-cytoplamic constituents, Igs & other organ-specific Ags. • Extensive immune complex-mediated inflammatory lesions affecting Kidneys, Joints, Skin, Serous membrane and Lungs • Women are more affected (80%), usually those of childbearing age • HLA-DR2 or DR3 are predisposed to SLE Diagnosis: Antinuclear Ab - immunofluorescence Anti-DNA Ab (RIA/ ELISA) Dr Ekta, Microbiology

  27. Rheumatoid Arthritis (RA) • Symmetric polyarthritis with muscle wasting and subcutaneous nodules. • Associated with myocarditis, vasculitis & other disseminated lesions. • Presence of a circulating auto Ab called Rheumatoid Factor(RF) • RF- IgM directed against one’s own IgG Diagnosis : Latex agglutination test Dr Ekta, Microbiology

  28. Polyarteritis Nodosa • Necrotizing angiitis involving medium-sized arteries. Sjogren’s Syndrome • Triad of conjunctivitis sicca, dryness of the mouth with or without salivary gland enlargement, and RA. • May occur along with other collagen diseases. Dr Ekta, Microbiology

  29. Transitory Autoimmune Diseases • Follow certain infections or drug therapy. • Infecting agent or drug induces antigenicalteration in some self Ags. • Transient. • Undergo spontaneous cure when the infection is controlled or the drug is withdrawn. • Includes anemia, thrombocytopenia or nephritis. Dr Ekta, Microbiology

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