MECHANISM OF TISSUE GRAFT

REJECTION

-Dr. Nilesh Chandra

OBJECTIVES

REVIEW OF:

First set rejection

Second set rejection

Hyperacute, acute & chronic rejection

Ways to diminsh rejection response

TYPES OF GRAFT

Auto-graft

Iso-graft

Allo-graft

Xeno-graft

REJECTION

AUTOGRAFT ACCEPTANCE

FIRST SET REJECTION

SECOND SET REJECTION

MEMORY OF ALLOGRAFT REJECTION

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.

ROLE OF T-CELLS IN REJECTION

ROLE OF T-CELLS IN REJECTION

ROLE OF T-CELLS IN REJECTION

EFFECT OF HLA MATCHING

TIME COURSE OF GRAFT REJECTION

Hyperacute Rejection: within 1st 24 hours

Acute Rejection: within 1st few weeks

Chronic Rejection: months to years

Steps in the

hyperacute

rejection of

kidney graft

ACUTE REJECTION

Mediated by T-cells.

T-cell activation and proliferation

Massive infiltration of macrophages &

lymphocytes and tissue destruction

Graft Rejection

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.

IMMUNOSUPPRESSIVE THERAPY

General Immunosuppressive Therapy:

Mitotic Inhibitors: azathioprine, cyclophosphamide,

methotrexate.

Corticosteroids: prednisone, dexamethasone

Fungal immunosuppressant metabolites:

cyclosporin A, tacrolimus, rapamycin

Total Lymphoid Irradiation

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.

IMMUNOSUPPRESSIVE THERAPY

Specific Immunosuppressive Therapy:

Blocking co-stimulatory signals:

Blocking B7 by using CTLA-4 Ig.

IMMUNOSUPPRESSIVE THERAPY

Specific Immunosuppressive Therapy:

Blocking co-stimulatory signals:

Blocking B7 by using CTLA-4 Ig.

Monoclonal antibody directed against CD40L.

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.

SUMMARY

Types of graft

Physiology of graft rejection

Types of graft rejection

Clinical application

THANK YOU