Transplant Medicine - Antibody mediated rejection

Summary

This video explains antibody-mediated transplant rejection, a process where the recipient's immune system attacks the transplanted organ. It covers the various types of rejection, including hyperacute, acute, and chronic, and how the immune system's response leads to organ dysfunction. The video details the role of unique antigens in the donor organ, how antibodies bind to foreign cells, and the subsequent immune response. It also discusses immunosuppressive treatments, their side effects, and the importance of careful management of immunosuppression to prevent rejection while minimizing risks like infection and malignancy.

Takeaways

• 😀 Antibody-mediated transplant rejection occurs when the recipient's immune system targets the donor organ as foreign, leading to organ dysfunction.
• 😀 The two main types of transplant rejection are T-cell mediated and antibody-mediated, with the latter being divided into hyperacute, acute, and chronic rejection.
• 😀 Immunosuppressive agents are used to reduce organ rejection by suppressing the recipient's immune system.
• 😀 Antibody-mediated rejection begins when the host's immune system recognizes foreign antigens on the donor organ, leading to antibody production by activated B cells.
• 😀 The complement system plays a crucial role in antibody-mediated rejection, leading to cell injury, inflammation, and thrombosis in the transplanted organ.
• 😀 Hyperacute rejection occurs within minutes to hours of transplantation due to preformed donor-specific antibodies, often from prior transplants or blood transfusions.
• 😀 Acute rejection can occur at any point during the transplant period and is often due to reduced immunosuppressive therapy.
• 😀 Chronic rejection is typically linked to non-adherence to immunosuppressive medications and develops over time as low levels of donor-specific antibodies accumulate.
• 😀 Complement protein 4D is a key marker used to distinguish antibody-mediated rejection from T-cell mediated rejection.
• 😀 Treatment for antibody-mediated rejection includes increasing immunosuppressive therapy, plasmapheresis, intravenous immunoglobulin, and monoclonal antibodies such as eculizumab.

Q & A

What is antibody-mediated transplant rejection?

Antibody-mediated transplant rejection occurs when the recipient's immune system produces antibodies against the foreign antigens present in the donor organ, leading to an immune response that attacks the transplanted tissue.

What are the two main types of transplant rejection?

The two main types of transplant rejection are T-cell mediated rejection and antibody-mediated rejection. Antibody-mediated rejection can further be divided into hyperacute, acute, and chronic rejection.

What role does the host's immune system play in transplant rejection?

The host's immune system recognizes the transplanted organ as foreign, triggering an immune response. The antigen-presenting cells of the host present foreign antigens to T-cells, activating B-cells to produce antibodies against the donor organ.

How does the complement system contribute to antibody-mediated rejection?

The complement system is activated when antibodies bind to foreign HLA molecules on the donor organ. This activation leads to a cascade of events, including the formation of the membrane attack complex, which damages donor cells and triggers inflammation.

What is hyperacute rejection, and why is it rare today?

Hyperacute rejection occurs when preformed donor-specific antibodies are present in high amounts before transplantation. It typically leads to graft rejection within minutes to hours. It is rare today due to improved HLA matching and compatibility.

What causes acute rejection, and how is it prevented?

Acute rejection typically occurs when immunosuppressive agents are reduced or ineffective, allowing the host's immune system to attack the transplanted organ. Careful management of immunosuppression, including tapering and adjusting doses, is required to prevent acute rejection.

How is chronic rejection different from acute rejection?

Chronic rejection develops slowly over time and is often due to poor adherence to immunosuppressive therapy. It results in low levels of donor-specific antibodies, leading to gradual rejection and failure of the transplanted organ.

What are some common treatments for antibody-mediated rejection?

Treatment options include increasing glucocorticoids, plasmapheresis to remove donor-specific antibodies, intravenous immunoglobulin to normalize the immune system, and monoclonal antibodies like eculizumab that inhibit complement activation.

What are the potential side effects of immunosuppressive treatments?

Immunosuppressive treatments can increase the risk of infections, malignancies, reactivation of latent infections, transfusion reactions, and allergic reactions. Specific drugs also carry their own risks, such as hypertension, osteoporosis, and increased susceptibility to certain viruses.

What is the role of HLA in transplant rejection?

Human Leukocyte Antigens (HLA) are unique to each individual and serve as markers that the immune system uses to identify foreign tissue. When a donor organ has different HLAs, the recipient’s immune system may recognize them as foreign and mount an immune response, leading to rejection.