Cell Mediated Immune Responses Cytotoxic CD8 T Cell Activation

When a virus infects a dendritic cell the virus is processed within the cytosol. Processed peptide then binds to the cleft in MHC-I and this complex is expressed on the dendritic cell surface. Next a naive CD8+ T cell recognizes this peptide-MHC-I complex and binds to it via its TcR. CD28, another molecule associated with the TcR, then binds to B7 on the surface of the infected cell. This interaction between CD28 and B7 transduces a signal to the T cell interior causing it to produce IL-2. IL-2 then feedsback on the T cell causing it to proliferate. The progeny of the proliferative response differentiate into cytotoxic T cells in response to IL-2.

Once the completely differentiated armed cytotoxic CD8+ T cells are formed in the secondary lymphoid tissues, they leave to search the body for infected target cells expressing the appropriate peptide/MHC-I complex. Equipped with new cell surface adhesion molecules and chemokine receptors, the CD8+ T cells migrate to the infected sites. T cell binding to target cells is initially mediated by adhesion molecules that are not specifically elicited by the antigen. This transient nonspecific interaction allows the TcR to bind to the peptide/MHC-I complex. If the TcR and the peptide/MHC-I complex are complementary, the binding affinity of the nonspecific adhesion molecules is increased causing a longer lasting and stronger bond. This TcR/MHC-I interaction also causes vesicles containing effector molecules to polarize along the T cell surface adjacent to the target cell, and finally it causes the release of these effector molecules. These effector molecules include perforin 1 which creates holes in the target cell membrane and granzyme (a.k.a. fragmentins), a protease that damages proteins vital to cellular functions. In addition, IFN-y is released which inhibits viral replication. Also, a cell bound effector on the T cell known as Fas ligand binds to Fas protein on the target cell inducing synthesis of proteins associated with apoptosis. Using these soluble and surface bound effector molecules the cytotoxic CD8+ T cell induces target cell death by apoptosis.

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