transplantation immunity.

TRANSPLANTATION IMMUNITY • When, as a result of disease or injury, an organ or tissue becomes irreparably damaged, or when an organ is congenitally defective or absent, a transplantation or grafting becomes necessary for restoration of function. • The tissue or organ transplanted is known as the transplant or graft. • The individual from whom the transplant is obtained is known as the donor and the individual on whom it is applied, the recipient. • The earliest application of transplantation appears to have been skin grafting. CLASSIFICATION OF TRANSPLANTS 1. Based on the organ or tissue transplanted, they are classified as kidney, heart, skin transplant etc. Based on the anatomical site of origin of the transplant and the site of its placement, grafts are Orthotopic grafts which are applied in anatomically normal sites as in skin grafts. Heterotopic grafts are placed in anatomically abnormal sites, as when thyroid tissue is transplanted in a subcutaneous pocket. 2. 3. 4. Transplants may be of fresh tissues and organs or of stored ones Transplants may be of living or dead materials. • Live grafts such as kidney or heart are expected to survive and function physiologically in the recipient and are called vital grafts. Nonliving transplants like bone or artery merely provide a scaffolding on which new tissue is laid by the recipient. They are called static or structural grafts. • 5. Transplants may be classified based on the genetic and antigenic relationship b/w the donor and recipient. An organ or tissue taken from an individual and grafted on himself is an autograft. A graft taken from an individual and placed on another individual of the same constitution is called an isograft • • Grafts made b/w identical twins is an example of isograft. • Grafts b/w two genetically nonidentical members of the same species are called allografts or homograft • Grafts b/w members of different species are called xenografts previously called heterograft. • Autografts and isografts – not considered foreign – rejection not elicited • Allografts and xenografts – considered foreign - rejected THE ALLOGRAFT REACTION • When a skin graft from an animal such as rabbit is applied on a genetically unrelated animal of the same species, the graft appears to be accepted initially. The graft is vascularised and seems morphologically and functionally healthy during the first two or three days. By about the fourth day, inflammation becomes evident and the graft is invaded by lymphocytes and macrophages. The blood vessels are occluded by thrombi, the vascularity diminishes and the graft undergoes necrosis, the graft assumes a scab like appearance and sloughs off by the 10th day. This sequence of events resulting in the rejection of the allograft is known as the first set response. • • • • • If, in an animal which has rejected a graft by the first set response, another graft from the same donor is applied, it will be rejected in an accelerated fashion. • Vascularisation commences but is soon interrupted by the inflammatory response. • Necrosis sets in early and the graph sloughs off by the 6th day. • The accelerated allograft rejection is known as the second set response. MECHANISM OF ALLOGRAFT REJECTION • The immunological basis of graft rejection is evident from the specificity of the second set response. • Accelerated rejection is seen only if the second graft is from the same donor as the first. • Application of a skin graft from another donor will evoke only the first set response. • An allograft will be accepted if the animal is rendered immunologically tolerant. • If suitable living cells like splenic cells from one pure line strain of animal is injected into fetal or neonatal animals of another inbred strain, the latter, when they grow up, will accept grafts from the former animal. This is due to the induction of specific immunological tolerance, against the donor tissues as a result of contact with them during embryonic life. • Transplantation immunity is predominantly cell mediated. • The first set response is brought about almost by T lymphocytes. • Humoral antibodies are also produced during allograft rejection. • Antibodies are formed more rapidly and abundantly during a second set response along with cell mediated immunity. • White graft response: when a graft is applied to an animal possessing the specific antibodies in high titer, hyper acute rejection takes place. The graft remains pale and is rejected within hours even without an attempt to Vascularisation • Seen in human recipients of kidney transplants. • Humoral antibodies may sometimes act in opposition to CMI, by inhibiting graft rejection. This phenomenon is called immunological enhancement. Example: if the recipient is pretreated with one or more injections of killed donor tissue and the transplant applied, it survives much longer. HISTOCOMPATABILITY ANTIGENS • IMMUNE RESPONSE AGAINST TRANSPLANTS DEPENDS ON THE PRESENCE IN THE GRAFTED TISSUE OF ANTIGENS THAT ARE ABSENT IN THE RECIPIENT AND THEREFORE REGARDED AS FOREIGN. • Antigens that participate in graft rejection are the transplantation or histocompatibility antigens. • The blood group antigens are important in transplantation. • The term major histocompatibility system in man is the human leukocyte antigen (HL-A ) system. • If the 2 parental strains have genotypes AA and BB, the F1 hybrid will be of genotype AB. • So it can accept tissues with genotypes AA and BB as it has both alleles A and B. • But transplantation in the reverse direction (from F1 to parent )will not succeed as strain AA will react against antigen B and strain BB against antigen A. FACTORS AFFECTING ALLOGRAFT SURVIVAL 1. The most important factor in allograft survival is the HLA compatibility. HLA typing identifies the HLA antigens expressed on the surface of leucocytes. Once a set of HLA compatible donors is available the best donors among them can be chosen by tissue matching. This is done by MLR or mixed leucocyte culture (MLC). As allograft rejection is an immunological process, immunosuppression will inhibit it. Can be done by irradiation, corticosteroids, ALS and immunosuppressive drugs. 2. 3. 4. 5. 6. • There are certain sites where allografts are permitted to survive, free from immunological attack ("immunologically privileged" site). • These sites include cartilage, brain, testes. • These are the areas which can accept allografts without rejection. • Lack of vascularity at the site also prevents graft rejection. • This is the reason for the success of corneal transplants. • Fetus is considered an intrauterine allograft as it contains antigens foreign to the mother • Reasons not clear • Some explanations given are: • Placental hormones – locally immunosuppressive • The mother forms antibodies against the foreign paternal MHC proteins, but the trophoblast layer of the placenta does not allow maternal T cells to enter the fetus • High concentration of alpha feto- proteins (fetal blood) – act as immunosuppressive agents – fetus is protected from immunological damage due to maternal leucocytes entering fetal circulation GRAFT VERSUS HOST REACTION • GRAFT REJECTION IS DUE TO THE REACTION OF THE HOST TO THE GRAFTED TISSUE (host versus graft response ). The contrary situation, in which the GRAFT MOUNTS AN IMMUNE RESPONSE AGAINST THE ANTIGENS OF THE HOST, is known as graft versus host reaction (GVH ). The major clinical features of GVH reaction in animals are retardation of growth, emaciation, diarrhea, hepatosplenomegaly, lymphoid atrophy and anemia, terminating fatally. The syndrome has been called the runt disease. • • TEXTBOOKS REFFERED Text Book Of Microbiology By R.Ananthanarayanan and C.K. Jayaram Paniker