Organ Transplantation and Immunity
Rejection is the Big Issue
Every one of us is different. The most important difference between us is in the way each of us presents antigens of foreign invaders to our T cells. Throughout time this difference has been essential for the evolution and survival of the human race, but it is one of the biggest obstacles for doctors to overcome when they are carrying out organ transplants.
A person's immune system reacts to a transplanted organ as if it were an infectious disease. The molecules of the organ's tissues are foreign to the recipient's and so his body mounts an immune response, producing T cells and antibodies that will kill the transplanted organ.
As medical research finds out more about the immune system and the potential of new drugs, ways of overcoming organ rejection are being developed.
Transplant Genes Are the Barrier
The HLA gene is responsible for making us different and therefore for fighting off foreign molecules, be they from an infectious disease or another person's tissues. The gene makes transplantation more difficult. It is also so complex it almost defies description! There are many millions of different HLA types.
Before a transplant, doctors select an organ with an HLA type matching that of the patient most closely. It is easier to find a well-matched organ amongst the patient's relatives than amongst unrelated people.
Drugs That Stop Rejection
Drugs have been developed to suppress the immune response and prevent the transplant from being rejected.
Corticosteroid, the natural hormone made in the adrenal glands, reduces transplant rejection. In 1960 it was found to be safer than radiation treatment to reduce kidney transplant rejection, but on its own it was not good enough.
Immuran is a drug that blocks the growth of lymphocytes, the type of cell that causes rejection.
Cyclosporin is a drug extracted from a fungus (Tolypocladium inflatum) discovered in soil in Norway. Jean-Francois Borel found that it stopped lymphocytes from causing transplant rejection. It is safer than other drugs because it paralyses lymphocytes rather than killing them. Since 1976 cyclosporin has dramatically improved the results of organ and bone marrow transplantation.
The Most Common Transplants Carried Out Today
Transplants differ in the strength of the immune response that they cause. Corneas are much better tolerated than livers, hearts or kidneys. Bone marrow, although technically the simplest transplant to perform, is the most difficult to control because it stimulates very strong immune reactions and requires very careful matching for HLA.
Corneal Transplants
• cures blindness due to diseases of the cornea
• the most successful type of transplant
• no shortage of cadaver donors
• rejection is uncommon and can be suppressed by corticosteroid eyedrops
Liver Transplants
• can cure liver failure, for example liver cirrhosis
• least likely of all organs to be rejected
• live donors can donate a lobe which will grow into a whole liver
• powerful immunosuppressive drugs are needed for the first five years
Heart Transplants
• can cure serious heart conditions, for example coronary artery disease
• rejection is the biggest problem
• severe shortage of donor organs
• drugs need to be taken for life
Kidney Transplants
• cures kidney failure
• rejection is the main problem
• shortage of dead donors but living relatives can safely give one kidney
• drugs must be taken for life
Lung Transplants
• can cure serious lung disease, for example cystic fibrosis
• currently at the experimental stage
• rejection is the main problem
• lung transplants are usually from dead donors
• a lobe from a living relative can be used
Pancreas Transplants
• may cure diabetes
• currently in the experimental stage
• leakage of pancreatic enzymes is the major problem
• living relatives can safely donate a bit of the pancreas
Bone Marrow Transplants
• cures leukaemia and some other blood diseases
• can lead to serious complications
• brothers and sisters are the best donors, but unrelated donors can be used
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Berkeley, Gloucestershire, England.
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