Immunology Lecture Notes 11-16 Type II Autoimmune disease Myasthenia gravis Autoantibodies to acetylcholine receptors Prevents Neurotransmission at synapse Blocking antibody (antagonist) causes receptor turn over Pemphigus vugaris ? antibodies to epidermis ? blistering of skin Type 2 diabetes ? insulin resistant ? can be agonistic or antagonistic abs to insulin receptor Insulin from the pancreas binds to its receptor and stimulates uptake of glucose from blood Type III Autoimmune disease Systemic lupus erythematosus (systemic autoimmune disease) Also called SLE or lupus Many IgG autoantibodies DNA, RNA polymerase, snRNPs, PolyA polymerase, myelin, platelets, blood clotting factors, mitochondria Extensive tissue damage, all these autoantiboides build up and form deposits of immune complexes Particularly damage kidneys ? glomerulonephritis and joints with arthritis. Highly variable course of disease Highest occurrence in African or Asian women, 1 in 500 Type IV Autoimmune disease T Cell mediated Not passed from mother to child (t cell mediated) Hashimoto?s thyroiditis CD4 TH1 cells become autoreactive and cause tissue damage in thyroid May involve autoantiboides Tissue is destroyed until it loses function Causes hypothyroidism Treat by giving the missing hormones IDDM ? type I or juvenile-onset diabetes Pancreas makes insulin to regulate blood glucose after meals Destruction of islet of Langerhans cells Usually present in children Abs and T cells attack Beta cells ? fatal if untreated Treatment ? inject insulin (may also lead to serum sickness) Study ? NOD mice Rheumatoid arthritis Abs against antibodies called rheumatoid factors ? 80% Complexes deposit in joints, activate C? Infiltration by CD4/CD8/plasma cells ? tissue damage ensues Treatment ? anti-inflammatory, immunosupprestion (anti-TNF alpha) ? infliximab Anti-CD20 depletes B cells, but a T cell disease?? Multiple sclerosis Attack of myelin sheath of nerve cells Disrupts signal transmission Motor weakness, vision, coordination diminishes Highly variable ? acute, slow or relapsing/remitting TH1 cells ? IFN gamma Also find plasma cells making IgG in CSF Study ? EAE experimental allergic encephalomyelitis Immunize mouse with MBP Transfer of T cells Current therapies Immunosuppresive drugs Corticosteroids ? general immune system but leaves open to infection Cyclosporine A blocks activated T cells Specifically Myestenia Gravis ? removal of thymus Plasma Pherisis for abs (type II or III) T cell vaccination Give ag specific T cells Induces regulatory T cells Or nject regulatory T cells for cell therapy Peptide blockage Have to know what peptide is Design blocking peptide Difficult with polymorphisms Monoclonal antibodies Anti-CD4 ? depletes all helper cells Anti-TCR ? delete specific T cellpopulations Anti-TNFalpha ? RA, crohn?s disease Anti-MHCII ? prevents T cell activation Oral Tolerance Feed mice MBP ? get no disease Not correlated in human
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