• 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
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
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.