AUTOIMMUNITY PART 1 BASICS

AUTOIMMUNITY PART 1 BASICS

• 1.
  PA9.4 DEFINE AUTOIMMUNITY. ENUMERATE AUTOIMMUNE DISORDERS DrIRA BHARADWAJ MCI TEACHER ID: PAT 2300569 KUHS FACULTY ID: M21512
• 2.
  TEXT BOOK REFRENCES •ROBBINS BASIC PATHOLOGY • HARSH MOHAN TEXTBOOK OF PATHOLOGY • DAVIDSON’S PRINCIPLES AND PRACTISE OF MEDICINE • OTHER STANDARD REFRENCES
• 3.
  SLO • DEFINITON OFAUTOIMMUNITY • BASIC MECHANISM OF AUTOIMMUNITY • ENUMERATE AUTOIMMUNE DISORDERS MEDIATED BY B LYMPHOCYTES • ENUMERATE AUTOIMMUNE DISORDERS MEDIATED BY T LYMPHOCYTES • QUESTIONS AT END OF SECTION 9.7
• 4.
  AUTOIMMUNE DISEASES DEFINITION A GROUPOF DISEASE CHARACTERIZED BY IMMUNE RESPONSE TO SELF ANTIGENS DUE TO LOSS OF SELF TOLERANCE
• 5.
  MECHANISM OF AUTOIMMUNITY BASICS Breakdownof self tolerance due to: • Genetic factors • Environmental factors
• 6.
  MECHANISM OF AUTOIMMUNITY BASICS:GENETIC FACTORS • Mutations in genes controlling tolerance • Familial predisposition • Females > males • Association with certain HLA types • Associated with other genes, which control response to immune regulation & microbes • Before proceeding further, I would like to remind you that each gene may have multiple roles & here we are focusing only on their functions as related to our topic of discussion
• 7.
  MECHANISM OF AUTOIMMUNITY GENETICFACTORS: HLA & SOME COMMON AUTOIMMUNE DISEASES HLA AUTOIMMUNE DISEASE ASSOCIATION HLA-B27 ANKYLOSING SPONDYLITIS, REACTIVE ARTHRITIS, UVEITIS HLA-DR2 SYSTEMIC LUPUS ERYTHEMATOSUS [SLE] HLA-DR3 SLE, AUTOIMMUNE HEPATITIS, SJOGREN SYNDROME, TYPE 1 DIABETES MELLITUS [DM] HLA-DR4 DM TYPE 1 HLA- DQ2&DQ8 COELIAC DISEASE
• 8.
  MECHANISM OF AUTOIMMUNITY GENETICFACTORS: NON HLA GENES INVOVED IN IMMUNE REGULATION & AUTOIMMUNE DISEASES GENES IN IMMUNE REGULATION FUNCTION IN IMMUNE REGULATION AUTOIMMUNE DISEASE ASSOCIATION PTNP22 PROTEIN TYROSINE PHOSPHATASE AFFECTS SIGNALING IN LYMPHOCYTES, ACTIVATING SELF REACTIVE T CELLS RHEUMATOID ARTHRITIS [RA], TYPE 1 DM, INFLAMMATORY BOWEL DISEASE [IBD] IL23R INTERLEUKIN 23 RECEPTOR INDUCES DIFFERENTIATION OF CD4+T CELLS INTO PATHOGENIC TH17 CELLS IBD, PSORIASIS, ANKYLOSING SPONDITLITIS CTLA4 AFFECTS REGULATORY T CELLS & SELF TOLERANCE RA, TYPE 1 DM IL2RA ALPHA CHAIN RECEPTOR FOR INTERLEUKIN 2, AFFECTS REGULATORY T CELLS & IMMUNE RESPONSE MULTIPLE SCLEROSIS, TYPE 1 DM
• 9.
  MECHANISM OF AUTOIMMUNITY GENETICFACTORS: NON HLA GENES INVOVED IN IMMUNE RESPONSE TO MICROBES & AUTOIMMUNE DISEASES GENES FUNCTION IN IMMUNE REGULATION OF MICROBIAL INFECTION AUTOIMMUNE DISEASE ASSOCIATION NOD2 expressed in Paneth & intestinal epithelial cells, controls resistance to gut commensal microbes INFLAMMATORY BOWEL DISEASE [IBD] ATG16 affects autophagy, role in maintaining epithelial barrier & defense against microbes IBD IRF5 interferon regulatory factor 5, has role in production of type 1 interferon SYSTEMIC LUPUS ERYTHEMATOSUS
• 10.
  MECHANISM OF AUTOIMMUNITY BASICS:ENVIRONMENTAL FACTORS • Molecular mimicry – cross reaction b/w antimicrobial Ab & self Ag due to certain similarities in molecular structure • Release of sequestered Ags, which normally do not come in contact with immune system during development hence the lymphocytes specific for such antigens are not deleted eg , sperm, lens, myelin
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  MECHANISM OF AUTOIMMUNITY BASICS:OTHER FACTORS • Infection associated with necrosis & inflammation, leading to activation of costimulatory molecules & loss of anergy (peripheral tolerance) • Altered display of self Ags (epitope spreading) due to chronic cell injury caused by UV, smoking, autoimmunity • Polyclonal lymphocyte activation due to any cause • Failure of apoptosis & clearance of apoptotic bodies • Failure of T suppressor cell function
• 13.
  AUTOIMMUNE DISEASES MEDIATEDBY B CELLS TYPE II HYPERSENSTIVITY • Autoimmune hemolytic anemia • Autoimmune thrombocytopenia • Autoimmune atrophic gastritis (intrinsic factor) • Myasthenia gravis • Graves disease • Goodpasture syndrome TYPE II & III HYPERSENSTIVITY • Systemic lupus erythematosus [SLE]
• 14.
  AUTOIMMUNE DISEASES MEDIATEDBY T CELLS TYPE IV HYPERSENSTIVITY Type I diabetes Multiple sclerosis Hashimoto’s thyroiditis Crohn’s disease [IBD] Rheumatoid arthritis Systemic sclerosis Sjogren’s syndrome