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Microvascular Research biology and pathology - part 8

Kích hoạt tế bào T-là điều cần thiết từ chối allograft. T-cell hoạt động liên quan đến chuyển vị hạt nhân của các yếu tố phiên mã cụ thể điều chỉnh biểu hiện của gen quan trọng cho chức năng tế bào T-. NF-kB đóng vai trò trung tâm trong quá trình này. Kích hoạt tế bào T là một cơ chế bắt đầu quan trọng của phản ứng miễn dịch và yêu cầu riêng biệt, nhưng hiệp đồng, tín hiệu. | 820 Part III Pathology stimulation of circulating host immune cells that encounter donor MHC antigens on allograft cell surfaces. T-Cell Activation T-cell activation is essential for allograft rejection. T-cell activation is associated with nuclear translocation of specific transcription factors that regulate expression of genes critical for T-cell function. NF-kB plays the central role in this process. The activation of T cells is a key start mechanism of immune response and requires two distinct but synergistic signals. The first signal is provided by a specific antigen and is delivered via the T-cell receptor. The second signal costimulatory signal is not antigen specific. Indeed many T-cell molecules may serve as receptors for costimulation. The most well characterized costimulatory molecule is CD28 which has two ligands B7-1 CD80 and B7-2 CD86 that are expressed primarily on APCs. Another molecule CTLA-4 is similar to CD28 and is also expressed on T cells. Although CTLA-4 binds B7-1 and B7-2 it transmits an inhibitory signal that serves to terminate the immune response. Cellular and Humoral Mechanisms of Allograft Rejection One or more attacks of acute cellular Figure 1 or humoral antibody-mediated rejection Figure 2 usually occur in almost half of the kidney transplant recipients despite active immunosuppressive strategies. Until recently most studies on the mechanisms of renal allograft rejection have focused on the central role of T cells and of other cellular mechanisms of tissue injury. It has been established that CD4 T cells are crucial in initiating most acute rejection episodes and that alloactivated CD4 T cells cytotoxic CD8 T cells monocytes macrophages and NK natural killer cells play a major role in cell-mediated mechanisms that eventually result in allograft destruction. Perforin and Figure 1 Acute cellular rejection. Lymphocytes L infiltrate beneath endothelium E with edema of intima I and subintimal layers B . H X E original magnification 100X.