מערכת החיסון המורכבת - תאי T

T-Cell Mediated Immunity

• T-cell-MHC interaction occurs in three locations:
  • Thymus (primary lymphoid organ): Educates T-cells to not strongly bind to self-MHC with a self-peptide (positive and negative selection). Educated cells have some affinity for self-MHC/self-peptide to recognize non-self later.
  • Lymphatic system (lymph, lymph nodes, spleen, Peyer's Patches): Organized structure with distinct B and T-cell zones. Dynamic tissue, swelling due to pathogen/antigen-specific proliferation. Antigen presentation to T-cells by APCs occurs here, transforming naive cells into effector cells.
  • Infected organ: Circulating T-cells enter lymph nodes via veins. If no relevant MHC-presenting APC encountered, they return to the bloodstream. Inflammation/pathogen triggers dendritic cell (DC) recognition, uptake, and transport to lymph node for T-cell encounter (in lymph nodes). Recognized T-cells become activated, re-enter the bloodstream as effector cells and travel to target tissue, executing their function.

T-Cell Activation & Trafficking

• Naive T-cells (mature T-cells leaving the thymus and not yet encountering antigen) migrate to secondary lymphoid organs and sample dendritic cells (DCs) presenting peptides.

• Effector T-cells are activated T-cells that recognize MHC:peptide on DC surfaces.

• DCs are the most effective T-cell activators.

• Naive T-cells enter lymph nodes through high endothelial venules (HEVs).

• Chemokines and adhesion molecules mediate T-cell entry into the lymph nodes.

  • Example: L-selectin for initial weak binding to vascular addressins (on HEV).
  • Further binding through integrins (conformational change in response to chemokines) for strong interaction with APC-expressed adhesion molecules, stopping T-cells at the desired location.
  • LFA-1 in naive and effector T-cells for target cell adhesion.
  • VLA-4 is highly expressed in activated T-cells.

• Chemokines attract T-cells to lymph nodes, increasing integrin binding affinity allowing the arrest of T-cells.

  • Example: CCL21 released by lymph node cells, attracting and activating T-cells through CCR7 receptor, which is expressed after interaction with selectins.

• DCs present antigens in lymph nodes, initiating clonal selection for the recognition of a specific antigen via clonal selection leading to T-cell activation.

Additional Concepts:

• Accessory cells: DCs play crucial role and are an example
• Clonal selection: A specific process of activation and proliferation that occurs when T-cells encounter an antigen for which they are pre-programmed.