Lecture 27 Studyguide - Immunology PDF

Activation of alloreactive T cells Proliferation Differentiation Effector functions Also, activation of alloreactive B cells leads to generation of alloantibodies that recognize graft antigens Alloantibodies most frequently recognize donor Class I and Class II MHC molecules Alloreactive antibodies e...

Activation of alloreactive T cells Proliferation Differentiation Effector functions Also, activation of alloreactive B cells leads to generation of alloantibodies that recognize graft antigens Alloantibodies most frequently recognize donor Class I and Class II MHC molecules Alloreactive antibodies engage effector mechanisms => complement, Fc receptor-mediated Endothelial cells express Class I MHC => Graft vasculature is prime target The transcript elaborates on the activation of alloreactive T cells, emphasizing the direct and indirect pathways by which donor antigens are presented to the recipient's immune system, ultimately leading to tissue rejection. Here's a breakdown: 1. **Direct Route**: - In the direct pathway, donor dendritic cells, represented as the green cells in the diagram, already carry antigens from the donated tissue and present them directly to recipient T cells. - This direct presentation occurs without processing by recipient antigen-presenting cells (APCs) and initiates the activation of alloreactive T cells. 2. **Indirect Route**: - Conversely, in the indirect pathway, recipient dendritic cells within the transplanted tissue capture and process donor alloantigens. - These processed antigens are then presented by recipient APCs to recipient T cells, leading to their activation. 1 3. **Lymph Node Response**: - Antigens presented by both donor and recipient APCs travel to the nearest lymph node, where they are presented to naive T cells. - This presentation leads to the proliferation and differentiation of T cells into effector T cells, such as CD4+ helper T cells and CD8+ cytotoxic T cells. 4. **Effector Functions**: - The activated effector T cells migrate back to the transplanted tissue, where they engage in various effector functions. - CD8+ cytotoxic T cells directly attack and kill graft tissue cells presenting alloantigens, while CD4+ helper T cells induce inflammation and cytokine production, contributing to tissue damage. 5. **Role of Antibodies**: - Alloreactive B cells are also activated in response to alloantigens, leading to the production of antibodies targeting MHC proteins on the donated tissue. - These antibodies recruit complement proteins and immune cells, further exacerbating tissue damage and rejection. 6. **Targeting Vasculature**: - The vasculature of the transplanted tissue, particularly endothelial cells lining blood vessels, is a prime target for the recipient's immune response. - Attack on the vasculature compromises blood flow to the transplanted tissue, ultimately leading to tissue failure. In summary, the activation of alloreactive T cells, along with the production of alloantigen-specific antibodies, orchestrates an immune response against transplanted tissue, resulting in tissue rejection. Understanding these pathways is crucial for developing strategies to prevent or mitigate rejection and improve transplant outcomes. 1 Effector mechanisms leading to allograft rejection Alloreactive CD4+ T cells, CD8+ T cells, and alloantibodies can promote allograft rejection, separately or in combination.