Download - Mechanism of tissue graft rejection
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MECHANISM OF TISSUE GRAFT
REJECTION
-Dr. Nilesh Chandra
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OBJECTIVES
REVIEW OF:
First set rejection
Second set rejection
Hyperacute, acute & chronic rejection
Ways to diminsh rejection response
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TYPES OF GRAFT
Auto-graft
Iso-graft
Allo-graft
Xeno-graft
REJECTION
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AUTOGRAFT ACCEPTANCE
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FIRST SET REJECTION
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SECOND SET REJECTION
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MEMORY OF ALLOGRAFT REJECTION
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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.
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ROLE OF T-CELLS IN REJECTION
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ROLE OF T-CELLS IN REJECTION
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ROLE OF T-CELLS IN REJECTION
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EFFECT OF HLA MATCHING
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TIME COURSE OF GRAFT REJECTION
Hyperacute Rejection: within 1st 24 hours
Acute Rejection: within 1st few weeks
Chronic Rejection: months to years
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Steps in the
hyperacute
rejection of
kidney graft
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ACUTE REJECTION
Mediated by T-cells.
T-cell activation and proliferation
Massive infiltration of macrophages &
lymphocytes and tissue destruction
Graft Rejection
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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.
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IMMUNOSUPPRESSIVE THERAPY
General Immunosuppressive Therapy:
Mitotic Inhibitors: azathioprine, cyclophosphamide,
methotrexate.
Corticosteroids: prednisone, dexamethasone
Fungal immunosuppressant metabolites:
cyclosporin A, tacrolimus, rapamycin
Total Lymphoid Irradiation
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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.
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IMMUNOSUPPRESSIVE THERAPY
Specific Immunosuppressive Therapy:
Blocking co-stimulatory signals:
Blocking B7 by using CTLA-4 Ig.
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IMMUNOSUPPRESSIVE THERAPY
Specific Immunosuppressive Therapy:
Blocking co-stimulatory signals:
Blocking B7 by using CTLA-4 Ig.
Monoclonal antibody directed against CD40L.
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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 InduceSpecific Tolerance.
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SUMMARY
Types of graft
Physiology of graft rejection
Types of graft rejection
Clinical application
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THANK YOU