If an adequate number of polymerized channels are assembled, the target cell will be unable to exclude ions and water, resulting in osmotic swelling and lysis. A second, equally important, function of perforin is to provide a means for introducing granzymes into the target cell. Granzyme B is a serine protease that preferentially cleaves protein substrates at aspartic acid residues. Target proteins that are recognized by granzyme B include IL-1 converting enzymes (ICE) or related cysteine proteases (caspases) that are themselves aspartic acid-directed. ICE and ICE-like proteases become catalytically activated upon cleavage at susceptible aspartic acid residues, so that by cleaving ICE, granzyme B initiates an ICE protease cascade that is comparable to the activation of the cascade induced by ligation of cell surface Fas. The net result is that the insertion of granzyme B into the cytoplasm of a target cell, like the ligation of Fas, initiates apoptotic cell death. Thus, by activating an apoptotic death pathway, a perforin/granzyme B-induced cascade of caspases can lead to the destruction of viral DNA genomes as well as the target cell genome, thereby eliminating potentially infectious DNA.
Step 4: Detachment of CTL
Step 5: Death of the target cell by osmotic lysis and apoptosis.
With regard to lymphocytes, programmed cell death plays a key role in controlling the size of the lymphocyte pool at several stages of lymphocyte maturation and activation. Immature lymphocytes that do not express functional antigen receptors undergo programmed death. After their maturation, if lymphocytes never encounter antigens, they die by apoptosis. Even if lymphocytes are activated by antigen, fractions of the progeny that do not receive sufficient growth factors or sustained stimulation also die. You can soon shop with a nice pharmacy offering cialis super active online pharmacy only here to benefit more.
Tags: Apoptosis, Carcinogenesis, Caspases, Inflammatory bowel disease