Transplantation: Videos & Practice Problems

Transplantation involves grafting living tissue—autografts from self, isografts from genetically identical donors, allografts from genetically different humans, and xenografts from other species. Transplant rejection occurs when recipient immune systems recognize donor human leukocyte antigens (HLAs) as foreign, triggering delayed cell-mediated hypersensitivity. Matching HLAs is crucial to prevent rejection, often requiring lifelong immunosuppressants. Bone marrow transplants replace impaired marrow but risk graft-versus-host disease (GVHD), where donor immune cells attack the host, causing inflammation in organs like skin and liver. Understanding antigen compatibility and immune responses is vital for successful transplantation and managing complications.

Transplantation

Transplantation, also known as grafting, involves transferring living biological tissue from one site to another or between organisms to restore function. The biological material used in transplantation is called graft tissue, which can include tissues, entire organs, or even individual cells. There are four primary types of grafts, classified based on the source of the graft tissue.

Autografts involve transplanting tissue from one part of a patient's body to another part of the same individual. For example, skin taken from a person's thigh and grafted onto a burn on their arm is an autograft. This type of graft is characterized by the source and recipient being the same person, minimizing the risk of immune rejection.

Isografts occur between genetically identical individuals, such as identical twins. In this case, tissue like bone marrow can be transplanted from one twin to the other. Since the donor and recipient share the same genetic makeup, isografts typically have a low risk of rejection.

Allografts involve transplantation between genetically different members of the same species. For instance, a kidney donated by an unrelated human to another person is an allograft. Because the donor and recipient are genetically distinct, the recipient’s immune system may recognize the graft as foreign, increasing the risk of rejection.

Xenografts refer to grafts sourced from a completely different species. An example is a heart valve taken from a pig and implanted into a human. Xenografts are more likely to trigger immune responses due to the significant genetic differences between species.

Understanding these types of grafts is essential for grasping the complexities of transplantation medicine. Each graft type presents unique challenges, especially regarding immune compatibility and the potential for graft rejection. The immune system’s response to transplanted tissue is a critical factor influencing the success of transplantation procedures.

Transplantation Example 1

Transplantation involves different types of grafts classified based on the source of the donor tissue. An autograft refers to a graft where the tissue is taken from the patient's own body, emphasizing the root "auto," meaning self. For example, treating a dog's burn wound with a skin graft harvested from another part of its own body is an autograft.

An isograft involves tissue transplanted between genetically identical individuals, such as identical twins. The root "iso" means equal or the same. For instance, a five-year-old girl receiving a bone marrow transplant from her identical twin exemplifies an isograft.

Allografts are grafts sourced from a genetically different member of the same species, with "allo" meaning other or different. A common example is a patient receiving a kidney transplant from a stranger, representing an allograft.

Lastly, a xenograft involves transplantation of tissue from a completely different species, where "xeno" means foreign. An example includes using a collagen implant derived from a cow to repair a human's rotator cuff injury.

Understanding these classifications is essential in transplantation biology, as the genetic relationship between donor and recipient influences graft acceptance and immune response. This knowledge aids in selecting appropriate graft types for clinical applications and anticipating potential complications such as rejection.

Individuals who have damaged or deteriorating heart valves commonly get heart valve replacement surgery. A biologic or tissue valve replacement surgery commonly replaces the patient’s damaged heart valves with pig heart valves. This surgery is an example of what type of tissue graft?

• A. Isograft.
• B. Allograft.
• C. Autograft.
• D. Xenograft.

Answer: (D)

Sydney requires a kidney transplant, & she receives one from her older sister, Becca, who is 2 years older. What type of transplant is this?

• A. Isograft.
• B. Autograft.
• C. Allograft.
• D. Xenograft.

Answer: (C)

Transplant Rejection

Transplant rejection occurs when the recipient's immune system identifies the donated graft tissue as foreign and mounts an attack against it. This immune response is primarily driven by differences in cell surface antigens known as human leukocyte antigens (HLAs), which are a subset of major histocompatibility complex (MHC) molecules. HLAs play a crucial role in enabling the immune system to distinguish self from non-self, making them essential for transplant compatibility. The greater the antigenic disparity between donor and recipient HLAs, the more vigorous the transplant rejection tends to be.

HLAs include both MHC class I and MHC class II molecules, which present antigenic peptides to T cells, triggering immune responses. Transplant rejection is largely mediated by type IV hypersensitivity reactions, also called delayed-type hypersensitivity, which involve T cell–mediated immune overreactions. This is especially relevant in allografts (transplants between genetically different individuals of the same species) and xenografts (transplants between different species), where genetic differences in HLAs are pronounced.

The challenge in transplantation lies in the extensive genetic variability of HLA genes, which significantly reduces the likelihood of finding a perfect donor-recipient match. This genetic diversity explains why transplant recipients often face long waiting lists and why close relatives, particularly identical twins, are the most compatible donors due to their genetic similarity.

At the cellular level, dendritic cells from the recipient process and present donor HLAs to naive cytotoxic and helper T cells, activating these T cells and initiating a cell-mediated immune response against the graft. This immune activation leads to the destruction of the transplanted tissue, manifesting as transplant rejection.

To prevent rejection, transplant recipients typically require lifelong immunosuppressant therapy, which dampens the immune response and helps maintain graft survival. This necessity underscores the complexity and seriousness of transplant rejection in clinical practice.

If the cell surface molecules of transplanted tissue do not match the recipient’s cell surface molecules, the transplanted tissue may be targeted by the recipient’s immune system and rejected. Which surface structures on the transplanted tissue are most likely to cause transplant rejection?

• A. MHC molecules.
• B. Rh antigens.
• C. MLB molecules.
• D. ABO antigens.

Answer: (A)

Which of the following is a non-autoimmune type IV hypersensitivity?

• A. Autograft transplant rejection.
• B. Allograft transplant rejection.
• C. Type I diabetes mellitus.
• D. Multiple sclerosis.

Answer: (B)

Graft-Versus-Host Disease (GVHD)

Graft-versus-host disease (GVHD) is a serious complication that can occur after a bone marrow transplant, which essentially replaces the recipient's immune system with that of the donor. Bone marrow transplants are often necessary for patients with conditions such as leukemia or sickle cell disease, where the recipient's bone marrow is functionally impaired. Before the transplant, the recipient's bone marrow and immune system must be destroyed or suppressed, typically through chemotherapy or radiation. This step is crucial to prevent the recipient's immune system from attacking the donor's immune cells, particularly donor T cells, which would result in transplant failure.

GVHD arises only after a successful bone marrow transplant when the donor's immune cells recognize the recipient's tissues as foreign and begin attacking them. This immune response is essentially the reverse of typical transplant rejection, where the host's immune system attacks the graft. In GVHD, the graft (donor immune cells) attacks the host (recipient's body). The donor bone marrow produces new blood and immune cells, but these donor immune cells can cause inflammation and damage to key organs such as the skin, liver, and gastrointestinal tract.

Because the recipient's immune defenses are weakened following the transplant, the donor immune cells can inflict significant harm, making GVHD a potentially life-threatening condition if not properly managed. Understanding the balance between immune suppression and immune function is critical in bone marrow transplantation to minimize the risk of GVHD while ensuring successful engraftment of donor cells.

Graft-versus-host disease typically occurs due to:

• A. A bone tissue allograft.
• B. A bone marrow autograft.
• C. A bone marrow allograft.
• D. A thyroid tissue allograft.

Answer: (C)

Here’s what students ask on this topic:

What are the different types of grafts used in transplantation?

Transplantation involves four primary types of grafts based on the source of the biological material. Autografts are tissues transplanted from one part of a patient's body to another part of the same individual, such as skin grafts from a thigh to a burn site on the arm. Isografts come from genetically identical donors, like identical twins, where the tissue is transplanted between genetically identical individuals. Allografts are sourced from genetically different members of the same species, such as a kidney transplant from an unrelated human donor. Lastly, xenografts involve transplantation of tissue from a different species, for example, a pig heart valve implanted into a human. Understanding these types helps in anticipating immune responses and managing transplant success.

How does transplant rejection occur and what role do HLAs play?

Transplant rejection happens when the recipient's immune system recognizes the donor graft's cell surface antigens, especially human leukocyte antigens (HLAs), as foreign. HLAs are proteins on cell surfaces that help the immune system distinguish self from non-self. If the donor's HLAs differ significantly from the recipient's, the immune system mounts a type IV hypersensitivity reaction, a delayed T cell-mediated response, attacking the graft tissue. This immune response is stronger with greater HLA mismatches, making close HLA matching critical to reduce rejection risk. Because of the high variability in HLA genes, finding a perfect match is challenging, often requiring lifelong immunosuppressant drugs to prevent rejection, especially in allografts and xenografts.

What is graft-versus-host disease (GVHD) and how does it differ from transplant rejection?

Graft-versus-host disease (GVHD) is a serious complication that can occur after a bone marrow transplant, where the donor's immune cells attack the recipient's tissues. Unlike typical transplant rejection, where the recipient's immune system attacks the graft, GVHD is essentially the reverse: the graft's immune cells recognize the host as foreign and cause inflammation and damage, especially in the skin, liver, and gastrointestinal tract. GVHD occurs because bone marrow transplants replace the recipient's immune system with the donor's, and if the recipient's immune system is suppressed or destroyed beforehand, it cannot defend against the donor immune cells. Proper matching and immunosuppressive treatments are essential to manage GVHD risk.

Why is HLA matching important in transplantation, and why is it difficult to find a perfect match?

HLA matching is crucial in transplantation because HLAs are the main proteins that allow the immune system to distinguish self from foreign. A close match between donor and recipient HLAs reduces the likelihood of transplant rejection by minimizing immune recognition of the graft as foreign. However, HLA genes are highly polymorphic, meaning there is a vast diversity of HLA types in the human population. This genetic variability makes it difficult to find a perfect or close match, especially among unrelated donors. Consequently, family members, particularly identical twins, are often the best donors due to their genetic similarity. The challenge of HLA matching contributes to long waiting lists for organ transplants.

What are the common immunosuppressive strategies used to prevent transplant rejection?

To prevent transplant rejection, recipients often require lifelong immunosuppressive therapy, especially after allografts and xenografts. These drugs suppress the immune system's ability to recognize and attack the transplanted tissue. Common immunosuppressants include calcineurin inhibitors (like cyclosporine and tacrolimus), corticosteroids, antiproliferative agents (such as azathioprine and mycophenolate mofetil), and mTOR inhibitors. These medications reduce T cell activation and proliferation, which are central to the rejection process. While immunosuppressants improve graft survival, they also increase the risk of infections and other complications, so careful monitoring is essential.