What is Acute Rejection?
Acute rejection is an inflammatory response that occurs when the recipient's immune system recognizes a transplanted organ or tissue as foreign and mounts an immune attack against it. This process typically occurs within days to weeks after transplantation and is a critical concern in organ transplantation.
Histological Features of Acute Rejection
The histological examination of tissues during acute rejection reveals several characteristic features:1. Inflammatory Infiltrate: A hallmark of acute rejection is the presence of an inflammatory infiltrate composed predominantly of lymphocytes, particularly T-cells, along with macrophages and other immune cells. These cells infiltrate the transplanted tissue, causing damage.
2. Endothelialitis: One of the key histological markers of acute rejection is endothelialitis, which involves inflammation of the blood vessel endothelium within the transplanted organ. This can lead to vascular damage and compromised blood flow.
3. Tubulitis: In the case of kidney transplants, tubulitis is a common histological finding, characterized by the infiltration of inflammatory cells into the tubular epithelium. This disrupts the normal function of the renal tubules.
4. Interstitial Inflammation: The presence of interstitial inflammation, where immune cells accumulate in the spaces between cells, is another feature observed in acute rejection. This can lead to tissue edema and impaired organ function.
5. Necrosis: In severe cases, acute rejection can lead to necrosis, or cell death, in the affected tissue. This is a result of the immune-mediated attack and subsequent tissue damage.
Diagnosis of Acute Rejection
The diagnosis of acute rejection relies on a combination of clinical, laboratory, and histological findings:1. Clinical Signs: Patients may present with symptoms such as fever, pain at the transplant site, decreased organ function, and other systemic signs of inflammation.
2. Laboratory Tests: Blood tests may reveal elevated levels of inflammatory markers, such as C-reactive protein (CRP) and an increase in serum creatinine in the case of kidney transplants.
3. Histological Examination: A biopsy of the transplanted organ is essential for confirming acute rejection. The tissue sample is examined under a microscope to identify the characteristic histological features mentioned above.
Mechanisms of Acute Rejection
Acute rejection is primarily mediated by the recipient's immune system, involving both cellular and humoral components:1. Cell-Mediated Immunity: T-cells play a central role in acute rejection. They recognize foreign antigens presented by the transplanted tissue and become activated. Activated T-cells then proliferate and attack the transplanted cells directly or indirectly by releasing cytokines that recruit other immune cells.
2. Humoral Immunity: B-cells can produce antibodies against the transplanted tissue, leading to antibody-mediated rejection. These antibodies can bind to antigens on the surface of transplanted cells, triggering a cascade of immune responses that result in tissue damage.
Treatment and Management
The management of acute rejection involves immunosuppressive therapy to mitigate the immune response and preserve the function of the transplanted organ:1. Corticosteroids: High-dose corticosteroids are often administered to reduce inflammation and immune activity.
2. Antithymocyte Globulin (ATG): ATG is used to deplete T-cells and reduce the immune attack on the transplanted tissue.
3. Calcineurin Inhibitors: Drugs like cyclosporine and tacrolimus inhibit T-cell activation and are commonly used in the long-term management of transplant recipients.
4. Monoclonal Antibodies: Agents such as basiliximab and daclizumab target specific components of the immune system to prevent rejection.
5. Plasmapheresis: In cases of antibody-mediated rejection, plasmapheresis can be used to remove antibodies from the recipient's blood.
Prognosis
The prognosis for acute rejection varies depending on the severity of the rejection episode and the promptness of treatment. Early detection and aggressive management are crucial for preserving transplant function and improving long-term outcomes. However, repeated episodes of acute rejection can lead to chronic rejection and eventual graft failure.
