Transplantation Immunology

Transplantation is a procedure that involves the removal of an organ or living tissue and placing it into a different part of the body or into a different person. Organ transplantations have become the therapeutic option of choice for many individuals with end-stage organ failure. Transplantation can offer the individual a definitive treatment for a given disease entity. Over the past 50 years, organ transplantation has become established worldwide, with ever-improving results, conferring an immense benefit to hundreds of thousands of individuals. Both solid organs and bone marrow–derived hematopoietic cells can be successfully transplanted for a number of different indications. Tolerance of the transplanted organ by the immune system of the host is achieved through the use of immunosuppressive and immunomodulating strategies. The main complications of transplantation are organ rejection or graft failure; however, chronic immunosuppression also carries the risk of serious complications, including potentially life-threatening infections.

Immunosuppressants are a class of drugs widely used in the management of autoimmune conditions and organ transplant rejection. The general effect is dampening of the immune response. There are multiple targets in the immune system, as well as varied mechanisms in inhibiting inappropriate immune activity. Biologic agents are medications derived from living organisms that target particular components of the immune system. The targets can be tumor necrosis factor (TNF), interleukins (ILs), or B- or T-cell activity. Calcineurin inhibitors halt the activity of calcineurin, a phosphatase involved in T-cell activation. Corticosteroids interfere with the cell cycle of inflammatory cells and modify the activity of other immune components. mTOR inhibitors are proliferation signal inhibitors, reducing immune-cell proliferation. Some immunosuppressants, such as cytotoxic agents, have antineoplastic activity; these are used in rheumatoid arthritis, as prophylaxis for transplant rejection, and for malignant diseases.

There are 29 blood group systems, among which the ABO group is the most important. Blood groups are determined by antigens that are surface markers on the RBC and consist of proteins and carbohydrates. Antigens are also found on platelets, leukocytes, and tissue cells and also exist in soluble form in body secretions such as breast milk, seminal fluid, saliva, sweat, gastric secretions, urine, and amniotic fluid. Individuals will naturally develop antibodies (Abs) against the ABO antigens they do not have. For this reason, determining an individual’s blood group is important prior to any blood product transfusion and prior to donating or receiving an organ transplant. If appropriate matching does not happen, a massive activation of the immune system and coagulation cascade will ensue, leading to shock, organ failure, and even death.

Although fresh whole blood was the only product in the early years of transfusion, the advent of whole-blood fractionation techniques has allowed for more efficient use of the various blood components. Fractionated transfusion products, prepared in blood transfusion centers, include RBCs, platelets, FFP, and cryoprecipitate. These products are transfused for different indications and each addresses different pathologies.

Transfusion-related complications occur during or after a blood product is given. These complications can be classified as immunologic, non-immunologic and acute, and delayed. Non-immunologic reactions are caused by the transmission of disease in blood products, and immunologic reactions are antigen-antibody–mediated. Symptoms can range from mild itching, chills, and urticaria (hives) to high fever, severe shortness of breath, jaundice, hypotension, or hemoglobinuria. Severe reactions can lead to death.