These immune killers cells can kill target cells by releasing cytotoxic granules such as perforin and granzymes. Why don't perforin/granzymes released by NK or T cells kill NK/T themselves?
Upon release in close proximity to a cell slated for killing, perforin forms pores in the cell membrane of the target cell, creating an aqueous channel through which the granzymes and associated molecules can enter, inducing either apoptosis or osmotic cell lysis.
To ensure that NK cells do not kill indiscriminately, the exocytosis of secretory lysosomes is a tightly regulated and highly ordered process.
First, an activating, lytic immunological synapse forms at the point of contact with the target cell, and there is a rearrangement of the actin cytoskeleton.
Second, the microtubule-organizing centre (MTOC) of the NK cell and the secretory lysosomes are polarized towards the lytic synapse.
In the third stage secretory lysosomes dock with the plasma membrane at the lytic synapse, before finally in the
Fourth stage fusing with the plasma membrane and releasing their cytotoxic contents.
Dominik, the key question is, what prevents the released contents (perforin/granzymes) from coming back to kill the releasing NK/CTLs?
Surface Cathepsin B Protects Cytotoxic Lymphocytes from Self-destruction after Degranulation
Kithiganahalli N. Balaji,1 Norbert Schaschke,2 Werner Machleidt,3 Marta Catalfamo,1 and Pierre A. Henkart1
JEM 2002
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