1. Autoimmune Diseases 20141

2. How Do the Immune Cells of the Body Know What to Attack and What Not To Attack ? 2014 2

3. All immune and blood cells develop from multipotent hematopoietic stem cells that originate in the bone marrow. Exit from BM, immature T cells undergo final maturation process in the Thymus that "educates" them to distinguish between self and non-self antigens. In normal persons, the autoreactive T- cells are deleted or inactivated. 20143 Immune Tolerance T lymphocytes are capable of recognizing an unlimited number of antigens.

4. Immune Tolerance 20144 The process of education of T-lymphocytes to not attack the "autoantigens" in addition to deletion or inactivation of autoreactive cells is called “Tolerance”

5. Autoimmune Diseases 20145 Autoimmune diseases arise when the induction and maintenance of immune tolerance fails. So here our immune system will attack self antigens.

6. These diseases result in cell and tissue destruction by: 1.antigen-specific CD8 cytotoxic T cells 2.or autoantibodies (antibodies to self-proteins) and the accompanying inflammatory process. 20146 Autoimmune Diseases

7. Exact reasons are unclear. However Genetics along with environmental factors (like hormonal influences, chemical, physical, and certain infections) may contribute to the tolerance failure & development of autoimmune diseases 2014 7 Causes of Autoimmune Diseases

8. Examples of autoimmune D Rheumatoid arthritis Hashimoto’s thyroiditis Graves disease Autoimmune hemolytic anemia SLE Inflammatory bowel disease Multiple sclerosis Type 1 DM Good Pasture S Others 20148

9. Any organ in the body can be affected & the result is inflammation of the skin, joints, kidneys, lung, heart, serosal surfaces…. 20149 SLE Like other autoimmune diseases, SLE has a familial tendency and affects women more than men, especially those in the 2 nd or 3 rd decades of life.

10. Tissue Transplantation 2014 10

11. Pancreas transplantation 201411

12. Grafts are divided into 4 types Auto graft: from one part of the body into another, and this graft usually survives without the need for immunosuppression providing that the tissue is healthy, well vascularized and there is no infection (e.g. transplantation of the skin from one part of the body into another). Isograft: From one individual to another who is genetically identical like the identical twin and here survival of the graft is the role. Allograft: Between two genetically non identical individuals from the same species and here rejection of the graft is the role if immunosuppression is not done. Xenograft: transplantation from another species and here rejection is very severe and it is unlikely for the graft to survive. 2014 12

13. HLA system & major histocompatibility complex (MHC) Human leukocyte antigen (HLA) or MHC molecules, present on the surface of cells. HLA system is genetically determined and this is the reason why donor organs from relatives of the recipient are preferred over unrelated donors. MHC molecules are divided into three groups:  MHC I and II – surface glycoproteins involved in transplantation reaction.  MHC III – encode complement components system. 2014 13

14. Class I HLA- antigens Expressed on all nucleated cells and platelets. CD8+ cytotoxic T-cells recognize virus or antigen only when having HLA-I (or MHC-I) Class II Antigens Largely restricted to antigen presenting cells (macrophages, dendritic cells and B- lymphocytes) 201414

15. Problems of Transplantation 1- Graft rejection (Host versus graft) 2- Graft versus host reaction (GVH) 201415

16. Graft Rejection It is a complex immunologic phenomenon as responses of the host directed against MHC on the donor graft. The rejection happens because the MHC (HLA) system of the donor is different from that of the recipient so that both cell mediated immunity and antibody response will be mounted against the transplanted tissue. The major types of hypersensitivity reactions involved are types II, III and IV. 201416

17. Kidney is the most common transplanted organ 201417

18. In renal transplantation there are (3) patterns of graft rejection: 1-Hyperacute rejection: The recipient have antibodies to the donors HLA Ag before transplantation. This occurs due to previous sensitization by previous transplantation, blood transfusion, multiple pregnancies and infections. In the transplanted kidney the surgeon will notice, just after vascular anastomosis, that the kidney will become cyanosed and secretes only few drops of bloody urine. 201418

19. 2-Acute rejection: This occurs few days after transplantation or after stoppage of the immunosuppressive therapy. The rejection will lead to endothelial injury, inflammation, thrombosis and necrosis of the transplanted tissue or organ. 201419

20. 3-Chronic rejection: Occurs after months- years The main lesion here is blood vessel intimal fibrosis that leads to ischemic glomerular injury, tubular atrophy, and shrinkage of the renal parenchyma together with mononuclear cellular infiltration. 201420

21. Methods of increasing graft survival 201421

22. 1- The best results will be obtained from finding of HLA compatible donor but unfortunately this is not available except from an identical twin and 1:4 of brothers or sisters. 2- When the donor is not compatible we should use immunosuppression like high doses of prednisolone or cytotoxic therapy. Both cause non- specific immunosuppression and the patient may suffer from opportunistic infections. 3- Now a days, antithymocytes antibodies are used. 4- Repeated blood transfusion in small doses from the same donor before transplantation increases the success of kidney transplantation. 201422

23. Before transplantation, we should destroy all the recipient marrow by total body irradiation and cytotoxic drugs, and this will make the patient (recipient) immunodeficient. After that the new bone marrow is transplanted, its cytotoxic T- lymphocytes will attack the recipient tissues. 201423 Graft Versus Host Disease (GVHD) Mainly occurs in bone marrow transplantation

24. The donor cells will attack the actively proliferating cells of the recipient resulting in gastroenteritis (nausea & vomiting), skin rash, jaundice, etc… 201424 The main cells involved in GVHD are CD8+ T-lymphocytes