Author/Editor		Rukavina, Daniel; Balen-Marunić, Sanja; Prpić, Larisa
Title		The role of perforin mediated cytoxicity in infections
Translated title		Vloga s perforinom pogojene citotoksičnosti pri okužbah
Type		članek
Source		Med Razgl
Vol. and No.		Letnik 39, št. Suppl 4
Publication year		2000
Volume		str. 95-100
Language		eng
Abstract		Lymphocyte dependent cytotoxicity plays an important role in protection against viral infections, infections with some intracellular parasites and in the immunologic control of tumor growth (immune surveillance). Experiments with perforin knockout mice, and clinical investigations clearly showed that at the molecular level, lymphocyte dependent cytotoxicity is mediated either by nonsecretory mechanisms (Fas/Fas L, TNF, TRAIL and TWEAK) or secretory mechanisms (Perforin granzymes - serine esterases). Perforin and granzymes are located in the granules of cytotoxic cells and are released in the contact area between effector and target cell. Perforin perforates target membranes forming pores which serves as conduits for the apoptotic action of serine esterases. CTL and NK cells are lymphoid cells able to exert contact-dependent cytotoxicity, and they are both endowed with strong cytolytic potential. Perforin mediated cytotoxicity is of crucial importance for our protection against some viruses (noncytopathic), and partly responsible for the control of other viral and intracellular parasite infections. Perforin mediated cytotoxicity also plays an important role in the immune surveillance against tumor growth.
Summary		Od limfocitov odvisna citotoksičnost ima pomembno vlogo v zaščiti pred okužbami z virusi, znotrajceličnimi zajedalci in pri imunskem nadzoru nad rastjo tumorjev. Poskusi z mišmi, ki ne morejo sintetizirati perforina (knockout) in klinične raziskave so pokazale, da je od limfocitov odvisna citotoksičnost pogojena z navzočnostjo nesekretornih (Fas/Fas, TNF, TRAIL in TWEAK) ali sekretornih (perforin in grancimi - serinske esteraze) molekul. Perforin in grancime najdemo v granulah citotoksičnih celic. Sprostijo se ob stiku efektorske celice s tarčno. Perforin naredi v membrano tarčnih celic pore, skozi katere prodrejo serinske esteraze in sprožijo apoptozo. S stikom pogojeno citotoksičnost so sposobni izzvati citotoksični limfociti T in celice NK. Ta način je izredno pomemben za gostiteljevo obrambo pred določenimi virusi (necitopatogenimi) in je delno odgovoren še za nadzor nad drugimi virusnimi in znotrajceličnimi zajedalskimi okužbami. S perforinom pogojena citotoksičnost je pomembna tudi pri imunskem nadzoru tumorske rasti.
Descriptors		CYTOTOXICITY, IMMUNOLOGIC INFECTION MICE T-LYMPHOCYTES, CYTOTOXIC KILLER CELLS, NATURAL HIV CYTOMEGALOVIRUS