• Most RBC antigens that cause transfusion reactions are also present in other body cells.
• Each tissue also has its own additional antigens.
• Therefore, transplanted foreign cells can produce an immune reaction in the recipient.
• The recipient’s immune system can resist foreign tissue cells just as it resists:
  • Foreign bacteria
  • Viruses
  • Foreign RBCs
• A transplant from one part of the same person (or animal) to another part is called an autograft.
• A transplant between identical twins is called an isograft.
• A transplant from one person to another or between animals of the same species is called an allograft.
• A transplant from a nonhuman animal to a human or between different animal species is called a xenograft.

Key Concept

• Foreign tissues contain antigens that can trigger an immune reaction in the recipient.
• Types of transplantation:
  • Autograft: Same individual
  • Isograft: Identical twins
  • Allograft: Different individuals of the same species
  • Xenograft: Different species

Transplantation of Cellular Tissues

• In autografts and isografts, the transplanted cells have almost the same antigens as the recipient’s tissues.
• Therefore, these transplanted cells usually survive normally and indefinitely if they receive an adequate blood supply.
• In xenografts, severe immune reactions almost always occur.
• These immune reactions cause the death of graft cells.
• The graft cells usually die within 1 day to 5 weeks after transplantation unless specific therapy is used to prevent the immune reaction.
• Different tissues and organs have been transplanted as allografts for experimental or therapeutic purposes.
• These include:
  • Skin
  • Kidney
  • Heart
  • Liver
  • Glandular tissue
  • Bone marrow
  • Lung
• With proper tissue matching, many kidney allografts have remained successful for 5 to 15 years.
• Liver and heart allografts have remained successful for 1 to 15 years.
• With improved tissue typing and immunosuppressive therapy, many transplanted organs survive for 20 years or more.

Key Concept

• Autografts and isografts usually survive because their antigens are almost identical to the recipient’s tissues.
• Xenografts usually undergo severe immune rejection within 1 day to 5 weeks unless treated.
• Successful allografts depend on proper tissue matching and immunosuppressive therapy.
• Modern transplanted organs can survive for 20 years or more.

ATTEMPTS TO OVERCOME IMMUNE REACTIONS IN TRANSPLANTED TISSUE

• Because transplantation of certain tissues and organs is very important, many attempts have been made to prevent antigen–antibody reactions.
• Some of these methods have shown clinical or experimental success.
• The most important antigens responsible for graft rejection are called human leukocyte antigens (HLAs).
• Each person has six HLA antigens on the tissue cell membranes.
• There are about 150 different HLAs.
• These produce more than 1 trillion possible HLA combinations.
• Therefore, it is almost impossible for two people, except identical twins, to have the same six HLAs.
• Development of immunity against any of these HLAs can cause graft rejection.
• HLAs are present on white blood cells as well as tissue cells.
• Therefore, tissue typing is performed using lymphocytes separated from the person’s blood.
• The lymphocytes are mixed with appropriate antisera and complement.
• After incubation, the cells are tested for membrane damage.
• Membrane damage is usually detected by measuring the uptake of a special dye through the lymphocyte membrane.
• Some HLAs are not highly antigenic.
• Therefore, an exact match of all HLAs between the donor and recipient is not always necessary for successful allograft acceptance.
• More advanced genetic testing helps achieve the best possible donor–recipient match.
• This has made grafting procedures less hazardous.
• The best transplant success occurs between siblings.
• Good success is also achieved between parent and child.
• Identical twins have an exact HLA match.
• Therefore, transplants between identical twins are almost never rejected because of an immune reaction.

Key Concept

• Human leukocyte antigens (HLAs) are the main antigens responsible for graft rejection.
• Each person has six HLAs, selected from about 150 different HLAs, creating more than 1 trillion possible combinations.
• Tissue typing is performed using lymphocytes.
• Genetic matching between donor and recipient reduces the risk of graft rejection.
• Identical twins have an exact HLA match, so their transplants are rarely rejected.

Prevention of Graft Rejection By Suppressing the Immune System

• If the immune system is completely suppressed, graft rejection does not occur.
• People with severely depressed immune systems may accept grafts without significant anti-rejection therapy.
• In people with a healthy immune system, allografts are usually rejected within a few days or weeks unless specific immunosuppressive therapy is used.
• T cells are the main immune cells responsible for destroying grafted tissue.
• Therefore, suppression of T cells is important to prevent graft rejection.
• Therapeutic agents used to suppress the immune system include:
• 1. Glucocorticoid hormones (or glucocorticoid-like drugs)
  • Inhibit genes that produce cytokines.
  • Especially inhibit interleukin-2 (IL-2).
  • IL-2 is essential for T-cell proliferation and antibody formation.
• 2. Drugs toxic to the lymphoid system
  • Block the formation of antibodies and T cells.
  • An important example is azathioprine.
• 3. Cyclosporine and tacrolimus
  • Inhibit the enzyme calcineurin.
  • Calcineurin activates transcription factors for IL-2 and other cytokines in T cells.
  • Inhibition of these cytokines suppresses T-cell activation.
  • It also suppresses T-cell-dependent B-cell activation.
  • These drugs suppress T cells without greatly affecting some other parts of the immune system.
• 4. Immunosuppressive antibody therapy
  • Includes antilymphocyte antibodies.
  • Includes IL-2 receptor antibodies.
• Immunosuppressive therapy leaves the person less protected against infections.
• Bacterial and viral infections may become severe.
• The risk of cancer is also increased in immunosuppressed people.
• This is because the immune system normally destroys many early cancer cells before they multiply.
• Successful transplantation of living tissues has become possible mainly because of immunosuppressive drugs.
• Improved immunosuppressive agents have made organ transplantation much more successful.
• The current goal of immunosuppressive therapy is to balance graft acceptance with fewer adverse effects of the drugs.

Key Concept

• Suppressing the immune system helps prevent graft rejection, mainly by inhibiting T-cell activity.
• Major immunosuppressive therapies include:
  • Glucocorticoids
  • Azathioprine
  • Cyclosporine
  • Tacrolimus
  • Immunosuppressive antibodies
• Immunosuppression increases the risk of infections and cancer.
• Modern immunosuppressive therapy has greatly improved the success of organ transplantation.