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Autoimmunity
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- 2. AUTOIMMUNITY Paul Ehrlich -Immune system could go awry and instead of reacting against foreign antigens, could focus its attack on Self Ag – named it “HORROR INTOXICUS” Mechanism of self tolerance normally protect an individual from potentially self reactive lymphocytes – failure –Autoimmunity
- 3. AUTOIMMUNITY ORGAN SPECIFIC AUTOIMMUNEDISEASE SYSTEMIC AUTOIMMUNE DISEASES 1. Immune Response against target antigen unique to single organ or gland 2. Manifestation is limited to that organ 3. Damage is caused either a. Directly by humoral or cell mediated effector mechanisms b. Antibodies overstimulate or block the normal function of the target organ 1. Immune Response directed toward a broad range of target Antigen 2. Involves a number of organs & tissues 3. Tissue damage is widespread a. Both from cell mediated Immune Response b. Direct cellular damage caused by auto-antibodies c. Accumulation of Immune Complex
- 4. ORGAN SPECIFIC AUTOIMMUNEDISEASE Diseases mediated by Direct Cellular Damage Diseases mediated by Stimulating / Blocking - Autoantibodies Lymphocytes and Auto-antibodies bind to cell membrane Antigens Cause Cellular lysis and / or Inflammatory response in the affected organs Damaged Cellular Structures will be replaced by connective tissues Function of organ declines In some Autoimmune Diseases, Antibodies act as Agonist – binding to hormone receptor – stimulating inappropriate activity – lead to an over production of mediators Conversely, Auto-antibodies may act as antagonists – bind to hormone receptor – but block the receptor function
- 5. ORGAN SPECIFIC AUTOIMMUNEDISEASE Diseases mediated by Direct Cellular Damage Hashimoto’s Thyroiditis Patient Middle Aged Women Target Thyroid gland Immune Cells involved Auto-antibodies & Sensitized Th1 cells specific for Thyroid Antigens Immune Response Auto Ab against number of thyroid proteins – Thyroglobulin & Thyroperoxidase – involved in the uptake of Iodine- binding interferes with Iodine uptake – decreased production of Thyroid hormone Th response – characterized by intense infiltration of Thyroid gland by Lymphocytes, Macrophages & Plasma cells – inflammation – Goiter – enlargement of Thyroid gland – physiological response - Hypothyroidism
- 6. ORGAN SPECIFIC AUTOIMMUNEDISEASE Diseases mediated by Direct Cellular Damage Auto Immune Anaemia Pernicious Anaemia Hemolytic Anaemia Drug Induced Anaemia Target Intrinsic Factor (Membrane bound intestinal protein on gastric parietal cells) RBC Antigen RBC Antigen Immune Cells involved Auto-antibody Auto-antibody Auto-antibody Immune Response •Intrinsic Factor facilitates uptake of Vit B12 from small intestine •Binding of Auto-Ab blocks Vit B12 uptake and absorption – necessary for Haemagtopoiesis – Number of functional mature RBC decreases below normal •Auto-ab binding with Ag on RBC triggers complement mediated Hemolysis •Ab mediated opsonization & phagocytosis of RBC Drugs – •Penicillin & Antihypertensive agent Methyl dopa – interact with RBC – make them antigenic •Opsonization, Phagocytosis & Complement meidated hemolysis
- 7. ORGAN SPECIFIC AUTOIMMUNEDISEASE Diseases mediated by Direct Cellular Damage Good Pasteur’s Syndrome Insulin – dependent Diabetes mellitus Target Basement membrane of Kidney Glomeruli & Alveoli of lungs Cells of Islets of Langerhans scattered throughout Pancreas Immune Cells involved Auto-antibodies Auto-antibodies & Cytotoxic T Lymphocytes (CTL) Immune Response •Antibody binding – Complement activation – Direct Cellular Damage – inflammation •Damage to glomerular & alveolar basement membrane – progressive kidney damage & pulmonary haemorrhage •Death in several months of the onset of symptoms Cells destruction mediated by cytokines released during DTH response , lytic enzyme release by activated M CTL infiltration – activation of M (Insulitis) followed by cytokine release Auto-Ab – contribute through complement & ADCC
- 8. ORGAN SPECIFIC AUTOIMMUNEDISEASE Diseases mediated by Stimulating / Blocking Antibodies Grave’s Disease Myasthenia gravis Target Thyroid gland Motor endplates of muscles Immune Cells involved Auto-antibodies Auto-antibodies Immune Response Auto-Ab binds to the receptors of TSH & mimic the normal action of TSH, activating adenylate cyclase – resulting in the production of thyroid hormones Unlike TSH, Auto-Ab are not regulated, consequently they overstimulate the thyroid. Auto-Ab binds to Acetylcholine Receptors on the motor endplates of muscles – blocking the normal binding of Ach Induces complement mediated lysis. Results in Progressive weakening of the skeletal muscles – ultimately destry the cells bearing the receptors
- 9. SYSTEMIC AUTOIMMUNE DISEASE SYSTEMICLUPUS ETHRYTHEMATOSUS MULTIPLE SCLEROSIS RHEUMATOID ARTHRITIS Patient Women – 20-40 of age Women – 40-60 of age Target Tissue Antigens such as DNA, Histones, RBCs, Platelets, Leucocytes & Clotting factors Myelin Sheath of nerve fibers Rhematoid Factor (Ig M) Immune Cells involved Auto-Antibodies Autoreactive T cells Auto-Antibodies Immune Response •Auto-Ab against RBC and Platelets – Complement Mediated Hemolytic anaemia and Thrombocytopenia •Immune complex with nuclear Ag – deposit on the walls of small blood vessels – complement mediated lysis – vasculitis & glomerulonephritis •Autoreactive T cells cause inflammatory lesions on Myelin Sheath of nerve fibers – infiltrate the brain tissue – cause inflammatory lesions – neurological disorders Auto-Ab (Rheumatoid Factor) – interact with determinants on the Fc region of Ig G Forming Ig M – Ig G complex – deposit in the joints – complement mediated Type III Hypersensitivity reaction
- 10. REFERENCES • Immunology –C V Rao, Alpha Science International Limited, 2016 • Kuby immunology –Judith A. Owen, Jenni Punt, Sharon A. Stranford; with contributions by Patricia P. Jones. New York : W.H. Freeman, 2013