FIGURE 23-34 Perforin- and granzyme-mediated cell killing by cytotoxic T cells. Upon recognition of a target cell (step 1), a cytotoxic T cell forms tight antigen-specific contact with the target cell. Tight contact results in the formation of a synaptic cleft, into which the contents of cytotoxic granules, including perforins and granzymes, are released (step 2). Perforins form pores in the membranes onto which they adsorb, and granzymes are serine proteases that enter through the perforin pores (step 3). Perforins are believed to act not only at the surface of the target cell, but also at the surface of its endosomal compartments after the perforin molecules have been internalized from the cell surface (step 4). Once in the cytoplasm, the granzymes activate caspases, which initiate programmed cell death (step 5).