Ultrastructure of cell mediated cytotoxicity

Contact dependent cell mediated cytotoxicity has been found to be executed by lymphocytes, macrophages, and even granulocytes. Cytotoxic effector cells of the lymphatic lineage are divided into cytotoxic T lymphocytes (CTL), mediating MHC related cytotoxicity, and in effectors mediating non-MHC restricted cytotoxicity such as natural killer (NK) cells, T lymphocytes displaying NK-like activity and lymphokine activated killer (LAK) cells. In morphologic studies these cells are hardly to be distinguished: they all show features of large granular lymphocytes (LGLs), which are characterized by a low nuclear to cytoplasmic ratio and azurophilic granules. Ultrastructurally lysosomal granules, showing an electron dense core that is either surrounded by numerous small vesicles or by a small electron translucent halo, have been found. Pore-forming proteins such as perforin, as well as serine esterases and proteoglycans have been pointed out in these granules. Specialties are parallel tubular arrays (PTA) in NK cells and nuclear inclusion bodies in LAK cells. Morphologically two types of killing event may be distinguished. In one way membrane lesions develop at the surface of target cells upon binding of effector cells and in advanced stages of cytolysis the target cells are surrounded by a completely disintegrated membrane. The nuclei, however, show only minor changes. In the other way, called apoptosis, the cell membrane of the targets remains intact, but the nucleus and cell organelles very early disintegrate intracellularly. Whether these morphologically different types of cell killing correspond to the functionally different pathways of cell mediated cytotoxicity remains to be resolved.