Mixed lymphocyte reaction

Mixed Lymphocyte Reaction (MLR) is a test used in immunology to measure the degree of HLA compatibility between donor and recipient in transplantation, to assess the strength of an individual's immune response, and in research to understand the complexities of the immune system. The MLR is based on the principle that T lymphocytes from one individual will recognize and respond to non-self Major Histocompatibility Complex (MHC) molecules on the lymphocytes of another individual. This response is a key aspect of the adaptive immune system's ability to distinguish self from non-self, which is critical in the context of organ transplantation, autoimmune diseases, and immune system disorders.

Procedure

The MLR involves co-culturing lymphocytes from two different individuals. One set of lymphocytes (the responders) are typically from the patient, while the other set (the stimulators) are from the potential donor or another individual. The stimulator cells are treated to prevent them from proliferating, ensuring that any proliferation observed is due to the responder cells' reaction to the foreign MHC molecules. Over several days, the responder T cells will proliferate in response to these foreign antigens, and this proliferation can be measured using various methods, such as DNA synthesis assays (e.g., incorporating bromodeoxyuridine (BrdU) or 3H-thymidine into DNA).

Clinical Significance

The MLR is particularly useful in the field of organ transplantation. By assessing the degree of immune response a recipient's lymphocytes have to a donor's antigens, clinicians can predict potential rejection reactions and select the most compatible donor, thereby increasing the chances of transplant success. Additionally, the MLR can be used to monitor the immune status of individuals, providing valuable information in the diagnosis and management of autoimmune diseases and immune deficiencies.

Research Applications

In research, the MLR is used to study the mechanisms of T cell activation and regulation, the role of different MHC molecules in immune responses, and the effects of various immunosuppressive drugs. It serves as a model for understanding how the immune system recognizes foreign antigens and initiates an immune response, which has implications for vaccine development, cancer immunotherapy, and understanding tolerance mechanisms in autoimmunity and transplantation.

Limitations

While the MLR is a powerful tool, it has limitations. The test is time-consuming and requires specialized laboratory equipment and expertise. Additionally, the results can be influenced by various factors, including the health status of the individuals from whom lymphocytes are collected and the specific protocols used for the assay. Furthermore, the MLR measures a general immune response and may not reflect the complexity of in vivo immune interactions fully.