The implantation of the non-self tissue into the body or the transfer of the living cells, tissues and organs from one part of the body to another or from one individual to another is known as transplantation. The individual who provides the graft is the donor and the individual who receives the graft is the receiver or the host. If we go back into the history, then the first experimental kidney transplantation took place in 1912 for which Alexis Carel got the Nobel Prize. In 1935, human kidney transplant was rejected in Russia. In this case the patient died due to the mistake in blood typing. in 1945, Mr. P.B. Medawar started the skin grafts. It is a kind of autograft. Mr. George Snell received the Nobel Prize in 1980 for the invention of Major HistoCompatibility genes (HLA). The successful kidney transplant between the identical twins in Boston took place in 1945 by Peter Bent Brigham Hospital.
The different types of transplant are as follows-
1) Autograft: In this case, the self tissue is transferred from one part of body to another in the same individual. Due to the genetic homology of the tissue, the immune system does not respond to it. for example, skin grafts, bone marrow transplantation, hair.
2) Isograft: The tissue is transferred between the genetically identical individuals.
3) Allograft: The tissue is transferred between the genetically different members of the same species. Most of the transplants are of this type. T cells plays a key role in the allograft rejection. In this case, both T- helper cells (CD4+) and cytotoxic T cells (CD8+) are present.
4) Xenograft: In this case, the tissue is transferred between different species. Xenotransplantation usually refers to the implantation of animal tissue in humans. It provides a new source of organs for humans. many different types of tissue can be transplanted, like, heart, kidney, liver or lung.
Some of the important factors which should be kept in mind for achieving the successful transplantation are as follows-
• proper knowledge of MHC haplotypes.
• Effective immunosuppression.
• Ability to identify and treat infections.
• Available donors.
Organ transplantation are illustrated here-
Liver transplantation- The end stage liver diseases (ESLD), Hepatic Disease, Congenital malformation, Congenital liver metabolic disorders, Acute liver failure, Chronic liver failure, Cirrhosis: Hepatitis B, Parasites: Hydatid disease of liver are the basic reasons for liver transplantation.
Renal transplantation- This is associated with as survival benefit for patients with end stage renal diseases (ESRD) when compared to dialysis. Even the marginal donor kidneys confer a significant survival advantage over maintenance dialysis. this is the preferred therapy for most of the patients with ESRD. The transplantation is cost- effective and improves the survival chances of the subject.
Major Histocompatibility Complex (MHC) is the gene complex whose alleles encode polymorphic cell surface glycoproteins involved in antigen recognition and presentation. MHC (HLA) matching between transplant donor and recipient greatly reduces the likelihood of rejection. The MHC loci are highly polymorphic with many alternative alleles at the locus. One haplotype is inherited from mother and another from father and the alleles are co-dominantly expressed. But we cannot match the MHC for most of the grafts as there is large polymorphism, less little time and merge donors. Therefore we require immunosuppression.
Generally, fetus is not rejected as a foreign agent from the mother's body as placenta acts as a barrier or filters which filters the anti-MHC antibodies. The outermost layer of the fetal tissue, Trophoblast is in direct contact with the maternal blood and it expresses either weak or no MHC. The hormone progesterone is immunosuppressive in nature. Sometimes, spontaneous abortions are triggered by the maternal immune response against the fetus.
The different phases of rejection are as follows-
a) Hyperacute rejection- the rejection occurs within minutes of transplantation. it occur due to the preexisting antibodies to the donor HLA antigens. the alloantigen, such as foreign MHC molecules, or alloantigen expressed on vascular endothelial cells.
b) Acute rejection - involves the cellular mechanism of CD4, CD8, Natural Killer cells and Macrophages. this rejection occurs within days or weeks after the transplantation. This is mediated by IgG antibodies against the endothelial cell.
c) Chronic rejection - this involve both humoral and cellular mechanism. this occurs over months or years. A form of chronic DTH (Delayed Type Hypersensitivity) or a response to chronic ischemia caused by injury to blood vessels. This results in the loss of normal organ structures.
Immunosuppression is a preventive measure. These are the drugs that inhibit or kill T lymphocytes. These anti-inflammatory agents reduce the immunogenicity of allografts. The immunosuppressants play a very important role in the organ transplantation. This increase the effect and the survival rate of organ transplantation by reducing their side effects like, organ toxicity, infection, tumors, etc.
After the transplantation, if the graft is rejected, the patient has to suffer through hypertension, fever, increase in the urine excretion, graft tenderness, increase in the graft size and myalgia or arthralgia.
The graft versus host disease (GVHD) occurs in the bone marrow of the recipients. It is initiated by the T cell recognition of the host alloantigens. These are characterized by skin rashes, jaundice and diarrhea.
Clinicians and medical experts claim that there are not enough organs. At least 150,000 patients in industrially developed countries badly need donor organs and tissues. Every 14 minutes another name is added to the national transplant waiting list and about 16 people die each day due to the lack of available organs for transplant. The tissues grafted are rejected by the immune system of the host organism as they detect it as the foreign graft tissue. at this stage, gene technology offers the possibility to breed the desired organs in animals. this technology makes it possible to humanize the bred organs and the immune system identifies the organ as its own tissue. thus, immune system rejection is prevented. For example, Chimpanzee whose DNA sequence differs from ours by only 2%, Baboon: their organs are too small for a large adult human and pigs has similar anatomy and physiology.
The various disadvantages of transplantation include:-
• Active invasive infection.
• Active malignancy.
• High probability of mortality rate.
• Unsuitable anatomic situation for technical success.
• Severe psychological or financial problem.
The gene which is responsible for the construction of a human organ makes the organism produce the organ additionally. This foreign gene can be inserted into an animal by DNA microinjection and retrovirus gene transfer. Thus, it is possible to humanize the bred organs by making certain genetic modifications. Transplantation provides us the means of restoring the function of a nonfunctional organ. Gene therapy is growing, and will definitely result into another revolution.
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