Monday, January 30, 2012

ORGAN TRANSPLANTATION


Transfer of tissue or organ from one place to another is called organ transplantation.
Types of graft
·       Autograft – one site to another site in the same body.
·       Allograft – From one person to another person in same species.
·       Isograft – Transplantation between identical twin.
·       Xenograft – Graft performed between different species.
 Graft rejection-
        Occur due to immune response. Later study demonstrated that T-lymphocyte play an essential role in orchestrating the graft rejection response. Cyto-toxic T- cells in the delayed type hypersensitivity and antibody dependent effector mechanisms all play a role.
Allograft rejection response is directed against a group of cell surface molecule called human leukocyte antigen (HLA). HLA is highly polymorphic and play a special role in immune response.
Two types of HLA molecules-
·       HLA class-1
·       HLA class-2
HLA class-1 antigen present on all nucleated cells while HLA class-2 antigen have a more restricted distribution and are expressed strongly on antigen presenting cell such as dendritic cell, macrophage, and  B – lymphocyte.
T- lymphocyte recognize peptide antigen bound to HLA molecule through their T-cell receptor and T-cell expresses a unique TCR that bind to a particular HLA peptide complex.
Types of graft rejection
·       Hyper acute graft rejection- occurs immediately.
·       Acute graft rejection- occurs within o6 months.
·       Chronic graft rejection- occurs within months or years after transplantation.
    


Hyper acute graft rejection
Occur due to presence of pre-formed antibody against HLA class-1 antigen expressed by the donar. They may occur from blood transfusion, failed transplant or previous pregnancy. This typeof rejection also occur if an ABO group incompatible organ graft is performed. Kidney transplants are particularly vulnerable to hyper acute graft rejection.

Acute graft rejection
It is mediated predominantly by T-lymphocyte but allo-antibody also play an important role. It is characterized by infiltration of mononuclear cells of the graft and includes cyto-toxic T cell, B cell, NK cell and macrophages. All types of grafts are susceptible to this form of rejection is about 25-50% cases.
Chronic graft rejection
Occur due to antibody mediated effector mechanism. All types of grafts are susceptible to chronic rejection and it is the major cause of allograft failure.
Risk factors of chronic graft rejection
·       Previous episodes of acute graft rejection
·       Degree of HLA mismatch
·       Long cold ischaemia time
·       Cyto megalo-virus infection
·       Raised blood lipid
·       Inadequate immuno suppression.
Immuno suppression agents
Commonly used agents are-
·       Azathioprine
·       Cyclosporine
·       Tacrolimus
·       Rapamycin
·       Cortico-steroids
·       Anti CD-25 monoclonal antibody.
Complications of immuno-suppression
·       Infection 
Bacterial
    Viral
    Protozoal
    Fungal.
·       Malignancy
Skin malignancy
NHL
Squamous cell carcinoma
Basal cell 
Malignant melanoma.

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