types of transplant; how grafts are rejected; how to increase graft life

1. MECHANISM OF TISSUE GRAFT
REJECTION
-Dr. Nilesh Chandra

2. OBJECTIVES
REVIEW OF:
 First set rejection
 Second set rejection
 Hyperacute, acute & chronic rejection
 Ways to diminsh rejection response

3. TYPES OF GRAFT
 Auto-graft
 Iso-graft
 Allo-graft
 Xeno-graft
REJECTION

4. AUTOGRAFT ACCEPTANCE

5. FIRST SET REJECTION

6. SECOND SET REJECTION

7. MEMORY OF ALLOGRAFT REJECTION

8. SPECIFICITY OF GRAFT REJECTION
 The specificity of second-set rejection can be
demonstrated:
 Graft an unrelated strain-C graft at the same time
as the second strain-B graft.
 Rejection of the strain-C graft proceeds according
to first-set rejection kinetics.
 The strain-B graft is rejected in an accelerated
second-set fashion.

9. ROLE OF T-CELLS IN REJECTION

10. ROLE OF T-CELLS IN REJECTION

11. ROLE OF T-CELLS IN REJECTION

12. EFFECT OF HLA MATCHING

13. TIME COURSE OF GRAFT REJECTION
 Hyperacute Rejection: within 1st 24 hours
 Acute Rejection: within 1st few weeks
 Chronic Rejection: months to years

14. Steps in the
hyperacute
rejection of
kidney graft

15. ACUTE REJECTION
 Mediated by T-cells.
T-cell activation and proliferation
Massive infiltration of macrophages &
lymphocytes and tissue destruction
Graft Rejection

17. CHRONIC REJECTION
 The mechanisms of chronic rejection include:
 Humoral response by the recipient.
 Cell-mediated response by the recipient.
 The use of immunosuppressive drugs greatly
increases the short-term survival of the
transplant, but chronic rejection is not
prevented in most cases.
 May necessitate another transplantation.

21. IMMUNOSUPPRESSIVE THERAPY
 General Immunosuppressive Therapy:
 Mitotic Inhibitors: azathioprine, cyclophosphamide,
methotrexate.
 Corticosteroids: prednisone, dexamethasone
 Fungal immunosuppressant metabolites:
cyclosporin A, tacrolimus, rapamycin
 Total Lymphoid Irradiation

22. IMMUNOSUPPRESSIVE THERAPY
 Specific Immunosuppressive Therapy:
 Monoclonal Antibodies against various surface
molecules:
 CD3 molecule of the TCR complex: otelixizumab
 High affinity IL-2 receptor : basiliximab, daclizumab
 CD4
 ICAM-1
 LFA-1
 TNF-α, IFN-γ, and IL-2.

23. IMMUNOSUPPRESSIVE THERAPY
 Specific Immunosuppressive Therapy:
 Blocking co-stimulatory signals:
 Blocking B7 by using CTLA-4 Ig.

25. IMMUNOSUPPRESSIVE THERAPY
 Specific Immunosuppressive Therapy:
 Blocking co-stimulatory signals:
 Blocking B7 by using CTLA-4 Ig.
 Monoclonal antibody directed against CD40L.

26. IMMUNE TOLERANCE TO ALLOGRAFTS
 Privileged sites accept antigenic mismatches.
These sites include:
 Anterior chamber of the eye
 Cornea
 Uterus
 Testes
 Brain
 Early Exposure to Alloantigens Can Induce
Specific Tolerance.

27. SUMMARY
 Types of graft
 Physiology of graft rejection
 Types of graft rejection
 Clinical application

28. THANK YOU