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Type 1 Diabetes- - IDDM Insulin Dependent Diabetes Mellitus

Type 1 Diabetes- - IDDM Insulin Dependent Diabetes Mellitus. TEAM - 窦甍 李德全 李帅 刘惠君 刘晓云 罗黎希. Contents. Type 1 diabetes(T1D), also named IDDM, is one of the most common autoimmune disease, affecting almost 20 million people worldwide. What is IDDM . IDDM. ◇ Factors Inducing IDDM.

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Type 1 Diabetes- - IDDM Insulin Dependent Diabetes Mellitus

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  1. Type 1 Diabetes- - IDDMInsulin Dependent Diabetes Mellitus TEAM - 窦甍 李德全 李帅 刘惠君 刘晓云 罗黎希 www.themegallery.com

  2. Contents Type 1 diabetes(T1D), also named IDDM, is one of the most common autoimmune disease, affecting almost 20 million people worldwide. What is IDDM • IDDM ◇ Factors Inducing IDDM • Insulin ◇ Immune Mechanism • Dependent Manifestations & Complications • Diabetes Therapy • Mellitus www.themegallery.com

  3. What is IDDM Factors Self Ag changes Immune Response • Heredity • Virus Infection • Environmental • Factors • Recognition of • specific self islet • βantigens • Effects of • immune cells • & molecules Disease Breaking Type 1 Diabetes Or IDDM. NOD Children & Adolescent Insulin-dependent • Breaking of • Immune • tolerance • Autoimmune • disease www.themegallery.com

  4. Factors Inducing IDDM • HLA-DQ β57 • Asp • Neutral AA • HLA-DQ α52 • Arg • Coxsackie B virus • Rubella virus • Mumps virus • Cytomegalovirus • Epstein-Barr virus • Etc. • Chemicals • Medicament Heredity Virus Environment www.themegallery.com

  5. Virus Infection • Changes of self-Ag into non-self-Ag Host cells become target cells Initiate immune response • Changes of host cell immune system function Ab Cytokines Immune tolerance Th1/Th2 • Cross reaction Virus & host cell have common Ag www.themegallery.com

  6. HLA expression Abnormal expression of Class Ⅱ MHC molecules Class Ⅰ MHC molecule High expression of Class Ⅰ MHC molecules β cell β cell Virus infection Environmental influence www.themegallery.com

  7. Mechanism of IDDM ◇ CD4+ T cells Autoimmune response β cell apoptosis and death CD8 + T cell Humoral immunity www.themegallery.com

  8. CD4+ T cell response Th1/Th2 unbalance Th0 Th1 • MHC Ⅱ abnormal • expression • Host cell turns into • APC • MHC Ⅱ + Self-Ag • Activate CD4+ T cell Cytokine secretion Th1 IFN-γ TNF-α Macrophage IL-1β TNF-α Apoptosis Fas-FasL pathway www.themegallery.com

  9. CD4+ T cell related response • Th0 cells mainly differentiate into Th1 cells, causing Th1/Th2 unbalance. • Th1 cells produce IFN-γ& TNF-α, inducing expression of Fas protein on islet βcell, and FasL expression on CTL or macrophage(IL-1β , NO, RNIs). • IFN–γcan activate NK cell ,which then hurt the target cells (β cell) with specific Ag . • IL-2 IL-12 • Th2 antagonizes Th1 effects. • IL-4and IL-10 can strongly inhabit Th-1 to produce IFN-γ, which can decrease the level of isletitis and improve β cells to produce insulin, to decrease the morbidity of IDDM www.themegallery.com

  10. CD8+ T cell response Perforin - Osmotic lysis Granzymes - Apoptosis IFN-γ TNF-α - Direct hurt of βcell Fas-FasL pathway - Apoptosis www.themegallery.com

  11. Pancreatic lymph node Islet Tc Granzyme Co-stimu- latory signals Fas FasL Perforin • • • • APC • • • • • • • • • • •  • • • • APC • • • • IL-1β TNF RNIs Apoptosis O2 NO • •  • Th1 • • • • • • • • • MØ • • Fas FasL IFN T- and B-cell clonal ex- pansion Th1

  12. Humoral Immunity • Insulin – Insulin Ab (IA) • Insulin receptor – Anti-insulin receptor Ab • Islet cell surface Ag (ICA)- Islet cell surface Ab • Glutamate decarboxylase (GAD) – Anti-glutamic acid decarboxylase Ab (GADA) www.themegallery.com

  13. Relationship CD4+ T cell response CD8+ T cell response Humoral immunity www.themegallery.com

  14. More non-self-Ag - More HLA expression of residual β cells More T cells response - More destruction of β cells β cells destruction - HSP GM ICA Cell lysis Residual cells Further destroy www.themegallery.com

  15. Children Adolescent NOD Polyuria Polydipsia Polyphagia A B T1D Ketonuria Glycouria Emaciation Fatigue Malaise D C Manifestation www.themegallery.com

  16. Coma Acute infection Acute Complications Complications Hypoglycemia Lactic acidosis Non-ketotic hyperosmolar syndrome Ketoacidosis www.themegallery.com

  17. Complications Skin infection Mucosa infection Chronic Complications Alzheimer’s disease Diabetic neuropathy Numbness Foot infection Large blood vessels problem Small blood vessel problem Diabetic retinopathy (Blindness) Diabetic nephropathy (Albuminuria Kidney Failure ) Heart disease (Myocardial infarction) Stroke www.themegallery.com

  18. Therapy Insulin therapy Gene therapy Islet transplantation • Subcutaneous injection (Lifetime) • Intravenous injection (Emergency) • Gene vector • Insulin-like substance • Transgenic mice model • stem cell • Islet β cell transplantation • Islet-Kidney united transplantation www.themegallery.com

  19. Thank You ! Dec. 7th, 2007 www.themegallery.com

  20. www.themegallery.com

  21. Regeneration of β cells www.themegallery.com

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