1. Let's Begin!

2. Autoimmune Hemolytic Anemia (AIHA) 05 级临六三班 曲玉娟 杨亭亭 叶 青 丁 盛 刘 扬 王占奎

3. 1. Introduction of AIHA 2. Mechanism and pathogenesis 3. Treatment

4. What is AIHA? Autoimmune hemolytic anemia (AIHA) is a disease in which the body attacks its own red blood cells (RBC). Abnormal RBC

5. AIHA/IMHA is a life threatening immune disease because ： Causing Hypoxia Result in blood clotting disorders and systemic inflammation syndrome

6. Clinical Manifestations Acrocyanosis( 手足发绀 ),fever, shivering, hemoglobinuria, pallor and jaundice dark red/ black urine etc

7. MECHANISM Abnormal of T cell immunological tolerance Immunological regulation disturbance After-Abs regulation disturbance

8. Abnormal of T cell immunological tolerance І T cell alternation activation pathway Ⅱ DC mediated T cell immunological tolerance disturbance Ⅲ Inhibition of activated T cell abnormal

9. Abnormal of T cell immunological tolerance І Normally, there are little soluable self-antigens in the organism.they can induce T cell immunological tolerance but the B call immunological tolerance. little dose soluble self- antigens B cell autoim mune B cell lack of Th cell self- tolerance T cell T cell B cell Inactivated B cell

10. T cell alternation activation pathway Self antigens abnormal virus infection. Drugs effection etc. Cross Reaction molecular mimicry: some microbe antigens have the similarities with self antigens,the microbe antigens activate T cells,then autoimmunity occur. Abnormal of T cell immunological tolerance

11. Ⅱ DC mediated T cell immunological tolerance disturbance In normal condition,there is an equilibrium between DC and T cell in lymph nodes Abnormal of T cell immunological tolerance T cell CTL Th cell Apoptosis AICD DC Bystander killing Apoptosis AICD

12. Under pathogenic condition,this equilibrium is disturbed,amount of autoimmune Th cells and CTL released into blood,then autoimmune dieases ocuur--AIHA Abnormal of T cell immunological tolerance

13. Fas gene absence CTLA-4 gene mutant Abnormal of T cell immunological tolerance Ⅲ Inhibition of activated T cell abnorma l AICD effect doesn't work

14. Immunological Regulation Disturbance Th1/Th2 disequilibrium and CKs network Treg abnormal

15. Th1/Th2 disequilibrium and CKs network ThP Th1 Th2 APC IL-12 IL-4 IL-2 、 IFN-γ 、 TNF-γ IL-4 、 5 、 6 、 7 、 8 、 9 、 10 Th0

16. AIHA Th2 Th1 DC subgroup disequilibrium, Treg abnormal etc.

17. Immune surveillance Th1 Cellular immunity Anti-virusAnti-mutationEliminate the decrepit and dead cells Antibodies Th2 Humoral immunity Anti-infection immunity

18. Th2 production increased IL-4 、 5 、 6 、 7 、 8 、 9 、 10 secretion increased Improve humoral immunity, B cells are activated excessively

19. IL-10 IL-10 is secreted by many kinds cells: activated thymocytes, B cell, CD45RA+ naive T cell, macrophages etc. IL-10 bcl-2telomeraseLifespan of B cell IL-10Proliferation of B cell IL-2,IL-4 IL-10 + Differentiation of B cell and type switching from IgG1 to IgG3

20. T reg abnormal CD4+CD25+T cells are 10% ～ 15% of all the T cells, they have higher affinity to self-peptide in thymus than the common T cells, and their function is not affected by APC

21. Ag CD25-CD25+ IL-10 TGF-β Co-stimulate factors on APC

22. After-Abs regulation disturbance CONCEPT: After-Abs regulation refers to the regulation of other regulators, such as Fc, complements and co-stimulators followed by the effects of Abs. including: Fc and Fc-receptor regulation Complement regulation

23. Fc and Fc-receptor regulation FcγR Ⅱ is a inhibiting receptor on the surface of MΦ. While FcγR Ⅰ and FcγR Ⅲ are activating receptors on the surface of MΦ

24. Fc and Fc-receptor regulation Ca²+ Fcγ R ⅱ Tyr residues FcγRi FcγRiii immunity-FcR.html

25. Fc and Fc-receptor regulation Ca²+ Fcγ R ⅱ Tyr residues FcγRi Fcγ Riii hemolytic RBC

26. Complement regulation Complement receptor type1(CR1) DAF Inhibit the activation of the complements by deactivating the C3/C5convertase in the classic pathway and alternate pathway

27. The classical pathway C3 C2 C4C4b C2a C3 convertase C3b C5 convertase C5C5b MAC CR1 DAF No homelysis of RBC

28. Complement regulation Genes of CR1 or DAF are lost or deficiency, the excessive activation of complements may attack self-RBC, and AIHA probably occurs.

29. The classical pathway C3 C2 C4C4b C2a C3 convertase C3b C5 convertase C5C5b MAC CR1 DAF The homelysis of RBC

30. Treatment Hematopoietic stem cells transplantion Monoclonal Ab treatment Peptide segment binding self-Ab competitively CKs treatment New immune inhibitor Liposome clodronat

31. The mechanism of AIHA is rather complicated, immune tolerance 、 immune regulation and after-Ab regulation etc are abnormal. Clearance of the relationship between these disturbance and development of AIHA, will provide new methods for diagnosis and treatment.

32. THANK YOU! HAVE A GOOD LUNCH!