Transplantation immunology

Rinkesh JoshiM.Sc Sem : 3 Bioscience ( Micro)09924113838Surat, Gujarat.

ContentsHistoryIntroductionClassification of graftsThe Immunology of Allogeneic TransplantationGenetics of graft rejectionTypes of rejectionRecognition of AlloantigensEffector Mechanisms of Allograft RejectionPrevention of graft rejectionGraft versus host reaction

History1944 : Medawar showed that skin allograft rejection is a host versus graft response. 1954 : The first successful identical twin transplant of a human kidney was performed by Joseph E. Murray in Boston1967 : The first successful liver transplant was done by Dr. Thomas E. Starzl1967 : The first heart transplantation by Christian Barnard 1968 : The first successful bone marrow transplant was done by E. Donnall Thomas

Introduction

Transplantation is a act of transferring cells, tissue, or organ from one site to another

Graft : Implanted cell, tissue or organ

Donor : Individual who provides the graft

Recipient or host : Individual who receives the graft

Classification of grafts

1) AutograftSelf tissue is transferred from one body site to anotherAntigen present in autograft is same as that present in

bodySo immune system recognizes the autograft antigen as

a self antigenNo immune response is elicitedAutograft survive through out the lifeEg., - Transferring healthy skin to burned area, - Use of healthy blood vessels to replace blocked coronary arteries, - Plastic surgery of skin.

2) Isograft

It is also called syngraftTissue is transferred between

genetically identical individuals of same species

In isograft the histo compatibility antigens are identical hence the graft survives and not rejected.

Eg in human isograft can be performed between two twins.

3) Allograft

Tissue is transferred between two genetically different members of same species

In allograft histocompatibility antigens are dissimilar hence immune response is elicited and graft is rejected

Eg., In humans graft is transferred from one individual to another

4) Xenograft

Tissue is transferred between two different species

Eg., Graft of human transferred to animalIn xenografts histocompatibility complex

antigens are so different that the graft is more vigorously rejected

The Immunology of Allogeneic Transplantation

• Alloantigens elicit both cell-mediated and humoral immune responses.

• Recognition of transplanted cells that are self or foreign is determined by polymorphic genes that are inherited from both parents and are expressed co-dominantly.

Genetics of graft rejection

Allograft rejection display specificity and memory

Rate of allograft rejection varies according to tissue involved

Skin graft are rejected faster than other tissue organ kidney or heart

If inbred mouse of strain A is grafted with skin from strain B , Primary graft rejection occur called first set rejection

When again strain A is grafted with skin from strain B , Secondary graft rejection occur called second set rejection

First- and Second-set Allograft Rejection

Recognition of Alloantigens

Direct recognition of Alloantigens

host T cells recognize intact allo-MHC molecules on the surface of the donor cell.

host T cells see allo-MHC molecule + allo-peptide as being equivalent in shape to self-MHC + foreign peptide and hence recognize the donor tissue as foreign.

This pathway is the dominant pathway.

Indirect recognition of AlloantigensDonor MHC is processed and presented by

recipient APCBasically, donor MHC molecule is handled like any

other foreign antigen

Activation of Alloreactive T cells and Rejection of Allografts

Donor APCs migrate to regional lymph nodes and are recognized by the recipient’s T cells

Alloreactive T cells in the recipient may be activated and they migrate into the graft and cause graft rejection

Effector Mechanisms of Allograft Rejection

Used by immune system to reject allograftIt is based on histopathological features or time duration of rejection after transplantation

There are three type of patterns

1. Hyperacute Rejection2. Acute Rejection3. Chronic Rejection

Hyperacute RejectionGraft is rejected within minutes to hours because

vascularization is rapidly destroyed. It occurs because the recipient has pre-existing

antibodies in circulation against the graft.Which could be induced by prior blood transfusions,

multiple pregnancies, prior transplantation, or xenografts.

Antibodies bind with donor endothelial cell.The antigen-antibody complexes activate the

complement system, causing massive thrombosis in the capillaries, which prevents the vascularization of the graft.

The kidney is most susceptible to hyperacute rejection.

1) Preformed Ab, 2) complement activation, 3) Neutrophil margination, 4) Inflammation, 5) Thrombosis formation.

Acute RejectionVascular and parenchymal injury mediated by T cells and

antibodies that usually begin after the first week of transplantation if there is no immunosuppressant therapy

Antibodies from after transplantation may also contribute to vascular injury.

Chronic rejection

Occurs in most solid organ transplantso Hearto Kidneyo Lungo Liver

Characterized by fibrosis and vascular abnormalities with loss of graft function over a prolonged period

ArthrosclerosisCell proliferationOcclusion

Prevention of graft rejection

I. Blood groupingII. Cytotoxic antibody testingIII. Tissue matchingIV. Immunosuppressive drugs

(azathioprine,cyclosporine,rapamycin, corticosteroids)

Graft versus host reaction

In some instance the graft tissue elicits an immune response against host antigen and that immune response is called graft versus host reaction

Graft versus host reaction brings damage to host cells and host

When grafted tissue has mature T cells, they will attack host tissue leading to GVHR.

Mechanism of GVHRGraft lymphocytes aggregate in the host

lymphoid organsGraft lymphocytes are stimulated by the host

lymphocyteStimulated lymphocytes of graft produce

lymphokinesLymphokines activate host T- cell which produce

polyclonal b-cell activationActivated b-cell react with the self antigens and

cause damage to the host cell

Clinical symptoms of GVHR

Skin rashEmaciation ( becoming thin)Retarded growthDiarrhoeaHepatomegalySplenomegalyIncrease in bilirubin productionBileducts are damagedanaemia

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