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    Autoimmunity Autoimmunity Presentation Transcript

    • • Introduction• Causes of Autoimmunity• Types of Autoimmunity• HLA & Disease• Autoimmune Diseases Linked To HLA Types• Immunosuppresive Drugs• Treatment• Mouse Models• Acknowledgement
    • Introduction• Autoimmune diseases is a group of disordersin which tissue injury is caused by humoral (byauto-antibodies) or cell mediated immuneresponse (by auto-reactive T cells) to selfantigens.• An autoimmune disorder may result in:–The destruction of one or more types ofbody tissue–Abnormal growth of an organ–Changes in organ function
    • Causes of Autoimmunity
    • Auto -immuneDiseasesHaemolyticautoimmunediseasesLocalisedautoimmunediseaseSystemicautoimmunediseases
    • 1. Haemolytic autoimmune diseases• Clinical disorder due to destructions of bloodcomponents. Auto Ab are formed against one’sown RBCs, Platelets or Leucocytes .• E.g. Haemolytic anaemia, Leucopenia,Thrombocytopenia, etc.
    • 2. Localised autoimmune disease• A particular organ is affected due to auto Abs.- For example:– Thyroiditis (attacks the thyroid)– Multiple sclerosis (attacks myelin coating ofnerve axons)– Myasthenia gravis (attacks nerve-musclejunction)– Juvenile diabetes or Type I DM (attacks insulin-producing cells)
    • Hashimoto’s thyroiditis• Hypothyroidism & destruction of thyroid cells.• Characterised by Goitre, enlarged thyroidgland.• Characterized by Type IV hypersensitivereactions.• It is a T-cell associated auto immune disease .
    • Myasthenia Gravis• Caused by auto antibody against muscleantigen & acetylcholine receptor antigen.• Characterized by ↑muscular weakness• Eventually death from respiratory failure .• Neuromuscular junction is severely affected.
    • Multiple Sclerosis• Degeneration of nerves CNS (brain andspinal cord).• Myelin disappear due inflammation.
    • Type I diabetes• β cells produce little or no insulin.• Heritable• Symptoms are like being very thirsty, hungry,tired or fatigued, urinating more often.
    • 3. Systemic autoimmune disease๏ Non organ-specific autoimmune diseases๏ Immune complexes accumulate in many tissuesand cause inflammation and damage.๏ For example: Systemic Lupus Erythematosus (anti-nuclearAb.): Harms kidneys, heart, brain, lungs, skin. Rheumatoid Arthritis (anti-IgG antibodies):Joints, hearts, lungs, nervous system. Rheumatic fever: cross-reaction betweenantibodies to streptococcus and auto-antibodies.
    • Systemic Lupus Erythematosus (SLE)• Skin disease due to the production ofantinuclear factor (ANF) .• In these patients, LE cell (a matureneutrophil) appears in blood & bonemarrow–Function – Phagocytosis in the presence ofANF.
    • Rheumatoid Arthritis• Disease of the joints.• Caused by the auto Antibody of IgM type,called as rheumatoid factors.• The synovial fluid of these patients containincreased no. of T-cells & macrophages.• Marked by inflammatory changes in thesynovial membrane.• In later stage, deformity develops.
    • Condition of RheumatoidArtheritis
    • HLA & Disease• Major histocompatibility complex (MHC) inhumans .• This group of genes resides on chromosome 6.• HLAs belongs to MHC class I present peptidefrom inside the cell which are degraded byproteasomes.
    • • HLAs corresponding to MHC class II presentantigens from outside of the cell to T-lymphocytes.• HLAs corresponding to MHC class III encodecomponents of the complement system.
    • Role of HLA1. In infectious disease2. In graft rejection3. In autoimmunity4. In cancer
    • Autoimmune diseases linked toHLA types• Diabetes• Graves disease• Hashimotos thyroiditis• Lupus• Multiple Sclerosis• Myasthenia gravis• Rheumatoid Arthritis
    • Immunosuppresive Drugs• Drugs that inhibit or prevent activityof the immune system.• They are used in immunosuppressivetherapy to:–Preventthe rejection of transplanted organsand tissues (e.g., bonemarrow, heart, kidney, liver)–Treat autoimmune diseases
    • • Immunosuppressive drugs can be classified intofour groups:o Glucocorticoids (suppress allergic, inflammatory andautoimmune disorders) .o Cytostatics (inhibit cell division) .o Antibodies (prevent the acute rejection and targetedtreatment of or autoimmune disorders) .o Drugs acting on immunophilins (Ciclosporin,Tacrolimus) .
    • Treatment• The key to treating autoimmunity is immunomodulation .• Some autoimmune diseases are treated with medicationsthat enhance specific symptoms.• Haemolytic anaemia: Treated with Vit B12• SLE : Treated with nonsteroidal anti-inflamatory drugs suchas ibuprofen or naproxen, antimalarial drugs, andcorticosteroids.– In more aggressive cases, immunosuppressive drugs maybe used.
    • Mouse ModelsHuman Disease Mouse ModelsRheumatoid Artheritis Collagen Induced Arthritis(CIA)Multiple Sclerosis Experimental AutoimmuneEncephalitis (EAE)Diabetes Non Obese Diabetic (NOD)Lupus MRLlpr