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  1. 1. Autoimmunity •Introduction •Immune tolerance •Pathogenesis of Autoimmunity •Classification of autoimmune diseases
  2. 2. Introduction • Autoimmunity is the failure of the body’s defence system in recognizing its own constituent parts as self, as a result of which an immune response is generated against its own cells and tissues. • Any disease that results from such an aberrant immune response is termed an autoimmune disease
  3. 3. Immunological Tolerance It is the ability of the immune system to identify the antigen as “self” and to protect it from an immunological response Tolerance occurs in 3 forms: • Central Tolerance • Peripheral Tolerance • Induced Tolerance
  4. 4. Central Tolerance • It refers to deletion of self reactive T and B lymphocytes during their maturation in central lymphoid organ (Thymus and Bone Marrow) • During the thymic maturation many self antigen are processed and presented to the developing T cells , and developing T cell that expresses a receptor for such a self antigen is negatively selected and depleted by apoptosis
  5. 5. Peripheral Tolerance • However, many of the T cells cannot be presented in the thymus hence T cell bearing receptors for such antigen escape into the periphery. • In the periphery these T lymphocytes are agained deactivated by 3 processes: – Anergy – Supression by regulatory T cells – Apoptosis
  6. 6. Development of Autoimmunity The failure to recognise the antigen as self will lead to development of immunological response The possible Etiology are: Genetic Suseptibility Microbial influnce
  7. 7. • Genetic susceptibility: Following evidence support the genetic factors for the development of autoimmunity – Familial predisposition: greater incidence in monozygotic twins – Role of HLA: Several autoimmune diseases are linked to HLA, the relative risk of association of HLA B27 and Ankylosing spondylitis is as high as 90 to 100
  8. 8. • Tissue Injury: A large variety of microbes have been implicated for triggering the autoimmunity due to following mechanism – Molecular mimicry: Viruses and microbes such as streptococci and klebsiella share a cross reacting epitope with the self antigen, the responses to such microbial antigen may attack self tissue ex: Rheumatic heart Disease
  9. 9. • Microbial infection with tissue necrosis and inflammation may lead to up regulation of resting APC’s in the tissue and subsequent breakage of anergy • The display of tissue antigens may be altered by infections , local tissue injury may lead to release of self antigen autoimmune response
  10. 10. Autoimmune Diseases • Organ Specific – Hashimato’s thyroiditis – Antoimmune Haemolytic Anaemia – Multiple Sclerosis – Goodpasture Syndrome – Autoimmune Thrombocytopenia – Autoimmune Orchitis – Type 1 Diabetes Mellitus – Myasthenia Gravis – Grave’s Disease – Autoimmune Hepatitis – Ulcerative Colitis
  11. 11. • Systemic – Systemic Lupus erythematosus – Rheumatoid Arthritis – Sjogren syndrome – Reiter’s syndrome – Systemic Sclerosis – Polyarthritis nodosa – Inflammatory myopathies