Immunoparalysis in Septic Shock Patients
Testo completo
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(11) . ȱ ȱȱȱ¢ȱȱȱȱȱȬĚ¢ȱȱ ȱ ȱ ȱ ¢ȱ ȱ ȱ ¢ȱ ¢ǯȱ ǰȱ ȱ ȱ ŘŖȱ ¢ȱ ǰȱȱǽ3Ǿȱ¢£ȱȱȱ¢ȱ¢Ě¢ȱȱȱȱȱ ¢ȱ ȱ ¢ȱ ȬĚ¢ȱ ȱ ǻǼȱ ȱ ȱ ȱ ȱ ȱ ǯȱ ȱȱȱǰȱȱȱȱȱȱȱȱȱȬȱȱ ȱęȱȱȱȱȱǰȱ¢ȱȱȱȱȱȱȱȱȱȱȱȱ ȱȱ¢ȱǽ4–6Ǿǯȱ¢ǰȱȱȱ ȱ ȱ ¢ȱ ȱ Ȧȱ ȱ ȱ ȱ ¢ȱ ȱ ȱ ¢ȱ ȱ DzȱȱȱȱȱȱȱȱcytomegalovirusȱǻǼǰȱȬȱȱ ǻǼǰȱȱȱǻ ǼDzȱȱȱ ȬȱĚDzȱȬȱ¢Dzȱȱȱ ȱǽ7, 8ǾȱǻTable 1Ǽǯȱȱ¢ȱ£ȱȱȱ ȱȱȱȱȱ¢ȱȱǰȱ¢ǰȱȱ ȱȱȱȱ ȱǻǯǯǰȱȱȱȱȱǰȱǰȱǯǼȱȱȱȱȱȱȱȱ ȱȱȱȱȱȱȱȱȱȱȱȱǻ Ǽȱ ǽ9Ǿǯȱȱȱȱȱȱȱȱȱȱ¢ȱȱȱ ȱ ȱ ȱ ǰȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ǽ1, ŗŖǾǯȱȱȱȱȱȱȱǻŗǼȱȱ ȱȱȱȱȱȱǰȱǻŘǼȱ ȱȱȱȱȱȱ¢ȱ£ȱ¢Ě¢ȱȱȱȱȱ ȱȱȱȱ¢ȱȱ ȱȱȱȱǰȱ ǻřǼȱȱȱȱȱȱȱȱȱǰȱǰȱę¢ǰȱǻŚǼȱȱ¢ȱȱ ȱȱǯ Variable. ȱĚ¢ȱ. ȱ¢. ǰȱȱ¢ǰȱȱȱ ȱȱǰȱȬȦ¢ǰȱ ǰȱ¢ȱȱǰȱ¢ȱ ȬȱǰȱȱȬȱȱȬ ȱȱ acquired infections. Patients population. ǰȱȬ. ¢ǰȱ. . ȱ. ȱ. ȱȂȱ¡. ȱȂȱ¡. ǰȱ¡ȱ. ȱǰȱ. Germs characteristics. ¢. ȱȱ ¢ȱę. ↑↑ or ↓ neutrophil count,. ↓ lymphocyte. ↑ȱȱȱ Nutritional status. Normal. Ȧ¡ ȱ . ȱ. ȱȱ. ȱ ȱ. Immunorestoration. ȱȱ. ¢ȱ. Late deaths. ǰȱȱȱ¢ǯ Table 1.ȱěȱȱȱȱȬȱȱǯ.
(12) ,PPXQRSDUDO\VLVLQ6HSWLF6KRFN3DWLHQWV KWWSG[GRLRUJLQWHFKRSHQ. ¢¢ȱȱȱDZȱȱȱ ŘǯŗǯȱȱĚ¢ȱ ȱȱȱŗşŝŖǰȱȱȱȱȱȱȱȱȱȱȱȱ ȱȱȱȱȱȱȱȱ¢ȱ¢ȱȱǻǼȱȱȱ ¢ȱȱȂȱȱȱȱǯȱȱȱȱȱ¢ȱȱȱȱ ȱ ȱ ȱ ȱ ¢ǯȱ ȱ ȱ ȱ Ȭȱ ȱ ¢ȱ ȱ ȱ Ȭȱ ȱ Ĵȱ ǻǼȱ ȱ ȱ ¡ǰȱȱǰȱȱȱȱȱȱ ǰȱĚǰȱȱȱȱ ȱ ȱ ȱ ȱ ¢ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ¡¢ȱȱǻȱȱ¢ȱ ǼȱȱȱȱȱȱȱĚ¢ȱǰȱȱȱȱȱȬαȱǻǼǰȱȱȱȱȱǻ Ǽǰȱ ȱ Ȭȱ ȱ ǻǼǰȱ ǯȱ ǻTable 2Ǽǯȱ ȱ ȱ ȱ ȱ ȱ ȱ ǻǼȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ¢ȱ ȱ ȱ ¡ȱ ¢ȱǰȱǻǼȱȱȱȱȱȱȱĚ¢ȱȱȱȱĴȱȱȱ ȱ ȱ ȱ ȱ ęȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ěȱ ȱ ȱ ȱ ǰȱ ȱ ǻǼȱ ȱ ȱ ǰȱ ȱ ȱ ȱ ȱ ¢ȱ ȱ ȱ ȱ ȱ ȱ ȱǽ6Ǿǯ ¢ȱȱȱȱǰȱȱȱĚȱȱȱȱ ȱ ȱ ȱ ȱ ȱ £ȱ ¢ȱ ǻǼȱ ȱ ȱ ȱ ¢ȱ ȱ ȱȱȱǰȱȱȱ¢ȱȱȱȱĴȱȱȱȱ ȱ. ¢. Source. ě. Interactions. . . ȱȱȱ immune system. ȱȱȱ. ȱȱ ȱ Ě¢ȱ. ȱȱ receptors. “. IL-1 receptor . ȱȱȱȱȱ lymphocytes. Inhibits the release of ȱȱ Ȭŗ. IL-6 receptor . . Promotes antiĚ¢ȱ. IL-1. “. ȱ¡ǰȱ ǰȱȬ. . IL-6. “. Ȭȱ. IL-12. ¢ǰȱǰȱ ȱȱȱ neutrophils, dendritic response cells. Promotes IFN-γ production. . IFN-γ. ȱ. ȱ. . ȱŞȱȱ. ¢ȱȱ immunoparalysis. ȱȱȱȱ ǰȱ ȬŗŘǰȱȱ ȬŗŞ. ǰȱȱȱDzȱ ǰȱDzȱ ǰȱǯ Table 2.ȱȱȱȬĚ¢ȱǯ. .
(13) . ,QIHFWLRXV3URFHVVDQG6HSVLV. !" #$%& "'() ! !'*"% +%)"' #' % #,. ȱȱ ȱȱȱ ȱȱ ȱȱȱȱȱȱȱȱȱ ȱ ȱ ȱ ȱ ęȱ ȱ ǻǼȱ ȱ ȱ Ȭαȱ ȱ ȱ ȱ ȱȱȱȱǻǼȱǻǯǯǰȱȱ ŗȬȱȱȱαȬǼȱȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ Dzȱ ǻǼȱ ȱ ȱ ȱ ȱ ěǰȱ ȱȱȱȱěȱ¡ȱȱěȱDzȱǻǼȱȱȱ ȱȱ ȱȱȱȱȱȱ2ȱȱȱȱ¢ȱȱDzȱȱ ǻǼȱȱȱ ȱȱȱ¢ȱȱȱȱ¢ȱȱȱ ȱǯȱ¢ǰȱȱ¢ȱȱȱȱȱȱȱǰȱ ȱ ǰȱ ȬĚ ȱ ǰȱ ¢ǰȱ ǰȱ ǯDzȱ ȱ ȱ ȱ ȱ ȱȱȱ¢ȱȱȱȱȱȱȱȱȱǻǰȱ ȬȱȱĴǼǯȱȱȱȱ¢ȱȱȱȱȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ¡ȱ ǻǼȱ ȱ¡ȱȱȱȱǽ11, 12Ǿǯ ȱȱ¢ȱǰȱȱȱ¢ȱȱȱȱȱȱȱȱ ǰȱȱȱȱȱȱȱȱȱ¢ȱȱȱǯȱ ȱ¡ȱ ¢ȱȱȱȱȱȱȱȱȱȱDZȱ¢ǰȱȱĴȱȱ¢ȱ ȱȱȬĚ¢ȱȱ¡ȱȱěȱȱȱ¢ȱǰȱȱȱ ȱȱ¢ȱȱȱȱȱȱȱȱȱȱȱ¢ȱȱěȱȱȱ¢ȱȱȱ¢ȱȱ¢ȱȱȱǻǼǯ ŘǯŘǯȱȱ¢ȱ ȱȱȱĚȱȱȱ¢ȱȱȱȱȱȱȱ ȱȱȱȱȱȱȱȱǰȱȱȱȱǰȱȱȱȱ¢ȱȱ ǻTable 3ǼǯȱȱȱȱȱȱĚ¢ȱǰȱȱȱȱȱȱȱ¢ȱ ȱǯȱ¢ǰȱȱ ȱ¢£ȱȱȱȱȱȱǻǼǰȱ¢ȱȬ Ě¢ȱȱ ȱȱȱȱȱȱȱȱȱȱȱ ȱ ȱ Ȭȱ ǯȱ ȱ ȱ ¢ǰȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱȱęȱȱǻǼȱȱȱȱȱȱȱȱȱȱ ȱ ȱ ȱ ȱ ȱ ěȱ Dzȱ ǻǼȱ ȱ ȱ ȱ ȬĚ¢ȱ ȱ ȱȱȱȱȬȱ¢Dzȱȱę¢ȱǻǼȱȱ Ȭȱȱȱ ȬĚ¢ȱȱȱȱȱȱȱȱȱȱȱȱ ȱȱǰȱȱ ǰȱȱȱȱ¢ǯȱǰȱȱȬ ȱ ¢ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ¢ȱ ǻǼȱȱȱ£ȱ¢ȱȱȱ ȱȱȱȱȱ ȱȱ¢ȱǯȱȱȱ¢ȱȱȱȱȬȱ ȱȱȱȱ¡ȱȱȱȱǯ ȱ ¢ǰȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ Ȭ ȱ ǰȱȱ¢ȱȱȱ¡ȱǻǼȱȱęȱȱ ȱ¢ȱȱȱȱ ȱȱȱȱ¡ȱȱȱȱȱǻȱǼȱȱǻǼȱȱȱ ȱȬȱȱ ȱȱ¡ȱȱȦȱȱȱȱȱȱ ȱȱȱȱȱǽ13, 14Ǿǯ.
(14) ,PPXQRSDUDO\VLVLQ6HSWLF6KRFN3DWLHQWV KWWSG[GRLRUJLQWHFKRSHQ. ¢. Source. ě. Interactions. ȬŗŖ. ȱȱȱ immune system. Immunosuppression. ȱȱȱȱȱ Ě¢ȱ. . Immunosuppression. ”. ȱhŘȱȬȱě. ȱȱȱȱ ȬŗŖ. Ȭβ. ȱȱȱȱȱ ¢. ȱȱ IL-4. ȱ hŘȱȱ . ǰȱȱ ȱǯ Table 3.ȱȱȱȬĚ¢ȱǯ. CDEFGH IJȱȱ ȱ ȱ ȱ ȱ ȱ ȱ ǯȱ ȱ ŗǰȱ ȱ ¢Ě¢ȱ ȱ ȱ¢ȱȱȱȱȱȱȱȱȱǯȱȱŘǰȱ ȱ¢Ě¢ȱȱ ȱ¢ȱ ¢ȱȱȱǯȱȱřǰȱ¢ȱȱȱ¢ȱȱ¢Ě¢ȱǯ. -. /0./12340.5 678 19738: 8;<99 /14.4/71 8<7=9/80<493 /7. >9 ;?@08;934A9B 6ȱ ŗǼDZȱ ȱ ęȱ. ȱȱ ȱȱȱ¢Ě¢ȱȱȱȱȱȱȱȱ ȱȱȱȱȱȱȱDzȱȱȱȱȱȱȱȱȱ ȱ ǰȱȱȱȱȱȱȬȱ¢ȱȱȱȱ. .
(15) . ,QIHFWLRXV3URFHVVDQG6HSVLV. KLMNOP KQR SNTRUVWR VXXYWR ZYW[KVLW\ NWP VW KQR KQVOP LWR] KQR ^_`a bORcNVUT NWP [NYTRT KQR ȱȱȱȱǯ. řǯȱȱȱȱ¢ ¢ȱ¢ȱȱȱȱȱȱȱȱȱȱ¢ȱȱ¢ȱȱȱȱĚ¢ȱȱȱȱȱȱȱȱȱȱȱȱȱ ȱȱȱ¢ȱȱǽ13, 15Ǿǯ ¢ǰȱěȱ¡ȱȱȱȱȱȱȱȱȱȱȱȱȱȱ£ȱ¢ȱȱȱȱȱȱȱȱȱȱȱ ǻTable 4Ǽǯȱ¡ȱȱȱȱǰȱȱȱȱȬȱěȱ¡ǯȱ ǰȱ¢ȱȱȱȱ¡ȱȱȱ Ȭȱȱȱȱȱȱ ȱȱȱĚ¢ȱȱ ȱȱȱȱȱȱǯȱǰȱěȱȬȱȱȱȱȱȱȱǰȱ ȱ ȬŘαǰȱ ȬŝȱαǰȱŞŜǰȱǯǰȱȱǯȱǰȱȱȱȱȱ ǰȱȱȱȱȱŗȱǻŗǼȱȱȱȱǻȬŗǼǰȱȱȱȱȬ ȱǰȱȱȱȱȱȱȱ¢¢ǯȱǰȱȱȱȱȱ ȱȱȱȬȱǰȱȱȱ¢Ȭȱȱ ȱȱŚ+ȱȱŘś+ȱȬ¢ȱȱǻǼǰȱ ȱȱȱ¢ǯȱȱ ȱ ȱ ȱ ¢ȱ ǰȱ ȱ ȱ ǻǼȱ ¢ȱ ȱ ȬĚ¢ȱ ¢ȱ ȱ Ȭβȱȱ ȬŗŖǰȱǻǼȱ ȱȱȱȱȬĚ¢ȱǰȱǻǼȱ. ȱ. . ¢ȱ. ↓ȱ Ȭȱ¡ ↓ȱȬα production. ȱȱ¢. Presently none. ȱ¢ȱ. ↑ȱȬǻǼŗȱ¡ ↑ȱȬŚǰȱȱ¡ ↑ȱ Ȭřȱȱ Ȭřȱ¡. ȱ . ↓ IL-7 receptor. . ↑ȱ ↓ lymphocytes. ȱȱȱ. ↑ȱȬŚǰȱȬŘś ↑ȱ¢Ȭȱȱ. ȬĚ¢ȱ¢. ↑ȱ ȬŗŖǰȱ Ȭŗřǰȱ ȬŚǰȱ ŗȱȱǰȱ Ȭβ ↑ȱ ȬŗŖȦȬα. Ȭǰȱȱ¢ȱȱȱȱ¢ȱDzȱȬǻŗǼǰȱȱȱDzȱȬŚǰȱ¢¡ȱ ¢¢ȱȱŚDzȱǰȱȱȱȱ¢¢ȱĴDzȱ Ȭřǰȱ¢¢ȱȱȱřDzȱ Ȭřǰȱȱ¢¢ȱ ȱȱřDzȱǰȱȱȱDzȱ Ȭβǰȱȱ ȱȬβǯ Table 4.ȱȱȱǯ.
(16) ,PPXQRSDUDO\VLVLQ6HSWLF6KRFN3DWLHQWV KWWSG[GRLRUJLQWHFKRSHQ. . ě. ¡ȱ. ↑ȱȬĚ¢ȱǰȱ↓ȱȬĚ¢ȱ ↓ȱȱ. . ↓ Immune cell number. ȱȱȱ¢ ¢ȱ. ȱȱ¢ . ȱ. ↓ȱȬĚ¢ȱ. Table 5.ȱȱȱ¢ǯ. defghijkle mngogopkm q mejjrs idt utv teimgkwige gxe yodomngerz {ofhgxs kyyfde mejjr |heredg. ȱȱǰȱȱȱȱȱȱȱȱ¢ȱȱȱȱ ȱǯȱ ¢ǰȱ ȱ ¢ȱ ȱ ȱ ȱ ¢ȱ ę¡ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱȱȱĴȱȱȱŘȱ¢ǰȱ ȱȱȱȱȱȱȱȱȬ Ě¢ȱȱ ȬŗŖȱȱ ȬŗǯȱȱĚ¢ǰȱȱȱȱ¡ȱȱȱ ȱ¢ȱ ȱȱ ¢ǰȱ ȱȱȱȱȱȱȱ ȱ ȱ ȱ ǰȱ ȱ ȱ ȱ ȱ ǰȱ ȱ ȱ ȱ ȱ ǰȱ ȱȱȱȱ¢ȱȱȱ¢ȱȱȱȱȱȱȱ ǻTable 5Ǽȱǽ16, 17Ǿǯȱȱȱȱȱȱ¢ȱȱȱȱȱěȱȱ ȱȱȱȱȱȱȱȱȱȱȱǰȱȱȱȱ¢ȱȱȱȱĚ¢ȱȱǰȱ¢ǰȱȱ¢ǯ. Śǯȱȱȱȱ¢ ȱȱȱȬȱ¢ȱȱȱ ȱȱȱȱȱȱ ȱȱ ȱȱȱ¢Ě¢ȱȱȱȱȱ ȱȬ ȱȱȱȱȱȱȱȱȱȱȱȱ¢ȱȱ ȱǽ18Ǿǯȱǰȱȱȱȱȱȱ¡¢ȱȱȱȱȱ¢ȱȱ ȱĴǰȱȱ¢ǰȱȱȱĴǯȱȱȱȱȱȱȱ ǰȱȱȱȱ ¢ȱǯ Śǯŗǯȱȱȱ ȱȱȱȱ¢Ě¢ȱȱȱ¢ȱȱȱȱȱ ¢ȱȱȱȱȱȱȱȱȱȱȱȱȱȂȱȱȱȱȱ ȱȱȱ ȱȱȱȱȱȱȱǯ ȱ ȱ ȱ ¢ȱ ǯȱ ¢ǰȱ ȱ ȱ ȱ ȱ ¢ȱ ȱȱȱ¢ȱ¢ǰȱȱȱȱȱ ȱǯȱȱ ȱǽ19Ǿȱȱȱȱěȱȱ Ȭȱȱȱřȱȱŝȱ¢ȱȱȱȱ ȱȱȱȱǰȱȱȱȱȱȱęȱȱȱ. .
(17) . ,QIHFWLRXV3URFHVVDQG6HSVLV. }~ ~}~ } } }~. ŘŚȱȱȱȱȱȱȱǽ5ǾDzȱȱȱǰȱȱȱ ȱȱȱȱ ȱ ȱȱȱȱǯȱȱ¢ǰȱȱȱǯȱǽŘŖǾȱȱȱ ȱȱ ȱȱ¢ȱȱȱǻǼȱ ȱȱȱȱȱ ȱřȱȱ şȱ¢ȱȱ ȱǰȱȱȱȱȱȱȱȱȱȱȱ¢ȱ ȱ ȱȱ¢ȱȱȱ¢ȱȱ ȱDžŗŚƖȱǽ17Ǿǯȱȱȱȱȱȱęǰȱȱȱȱȱ¢£ȱȱǻǼȱȱȱȱȱȱȱȱȱ ȱȱȱȱȱȱȱȱȱ¢ȱȱȱȱDzȱǻǼȱȱěȱ ȱȱȱǰȱ¢ǰȱȱȱȱ¢ȱȱȦȱȱǰȱȱȱ ȱȱȱŗŖȱ¢ȱȱȱDzȱȱǻǼȱȱȱȱ ȱ ȱȱ¢ȱȱȱȱȱȱǯ ŚǯŘǯȱȱȱȱȱ ȱ ȱǰȱ¢ȱȱ¢ȱȱȱȱ ȱȱȱȱȱȱȱ ȱȱȱǯȱȱȱȱ¢ȱȱȱǰȱǰȱȱȱ Ȭǰȱȱȱȱȱȱȱ¢ȱȱȱ¢ȱǯȱȱȱȱȱȱȱȱȱ¢ȱȱȱȱęȱ ȱĚȱ¢ȱȱ¢ȱȱȱȱȱȱȱȱǰȱ ȱ ȱ ǰȱ ȱ ¢ȱ ǰȱ ǯǰȱ ěȱ ȱ ȱ ȱ ¢ȱ ȱ ȱ ȱȱȱȱȱȱȱ ȱ Ȭȱȱȱȱȱ¢ȱȱ ¢ȱȱȱȱDZȱȱȱ¡ǰȱȱȱȱ¢ȱȱȱȱȱȱ ȱȱȱȱ¢ȱȱȱǯ ȱȱ¢ȱ¡ȱȱȱȱȱȱȱȱȱȱ ȱ ǰȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ǰȱ ȱ ȱ ȱ ěȱ Function. Cell. . . Lab technique. Runaround (h). Innate immunity. Neutrophils. ↑ Immature forms. . ǯȱ ¢ȱ analyzer. ŗǯś. ǰȱ ǰȱ. ŗǯś. ǯȱ ¢ȱ analyzer. Ŗǯś. ǯȱ ¢ȱ analyzer. Ŗǯś. . 12. ¢ȱ infections ¢. ↓ȱ Ȭ. ¢ȱ infections. ȱ immunity. ȱ¢¢. Lymphopenia. ¢ȱ infections. ȱȱ. . ¢ȱ infections. . Lymphocytes. ȱ. . ǰȱĚ ȱ¢¢Dzȱ ǰȱ¢Dzȱǰȱ¢ȱȱDzȱǰȱȦ¢¢ȱǯ Table 6.ȱȱ¢ȱȱȱȱȱǯ.
(18) ,PPXQRSDUDO\VLVLQ6HSWLF6KRFN3DWLHQWV KWWSG[GRLRUJLQWHFKRSHQ. ¡¢¢£¤¥£¦§ ¡¤¨ © £ ª£¡¦«¬£ª£¤© ® © £ ¯¢¨ ¤£¤©¬¡©°¤¦ ® ¦¢«¯¢£ ª£¨°¡©¬¦ °¤±¢±£¨. ȱȱěȱȱȱǽ14, 15, 21, 22Ǿǯȱ ȱȱȱȱȱȱ¢ȱȱ ¢ȱȱȱȱ ȱ ȱȱȱ¢ȱȱȱ¡ȱǯȱȱȱȱȱ ǻTable 6Ǽȱȱȱȱ¢ȱȱȱȱ¢ȱDzȱȱǰȱȱȬȬ¢¢ȱ ȱȱȱȱȱȱȱ¢ȱȱȱ¢ȱȱȱȱǽ23, 24Ǿǯȱ ȱǰȱ¡ǰȱȱȱ¢ȱ ¢ȱȱȱȱȱȱȱ ȱȱȱȱǻTable 7Ǽȱȱȱ¡ȱȱęȱȱȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ǯȱȱ ¢ȱ ǰȱ ȱȱȱ¢ȱȱȱȱȱ¢ȱȱȱǰȱȱȱȱȱȱȱ ȱȱȱȱȱȱǰȱȱ ǰȱȱǰȱȱ¢Dzȱ¢ǰȱȱȱȱȱȱ ȱȱȱȱȱȱȱȱȱ ȱȱȱȱȱȱȱȱȱěȱȱȱǽ25–27Ǿǯ ¢ȱȱȱ¢ȱǰȱȱȱȱȱȱȱȱȱȱȱ ȱȱȱȱ ȱȱȱȱȱǻǼȱȱȱȱȱȱȱȱ ȱȱȱȱȱȱȱȱȱȱȱǻǼȱȱȱȱȱȱȱǰȱ Function. Cell. . . Lab technique. Runaround (h). Innate immunity. ¢. ↓ȱŗŘŝ. ǰȱ secondary infections. ǰȱǰȱ ǰȱ . 5. ¡ȱ tolerance. Not clear. ȱǰȱ ǰȱǰȱ . 72. ↑ȱȬŗ. ¢ȱ infections. ǰȱ . ŗǯś. ŗŖȦȱ. . . 5. ȱ. ↓ȱ. ǰȱ secondary infections. . ŗǯś. ȱ¢¢. ↑ȱȱŚǰȱ. Not clear. ǰȱ . ŗǯś. ↑ȱ. . ǰȱ . ŗǯś. ȱŗŘŝ. ǰȱ secondary infections. ǰȱ . ŗǯś. Proliferation. ǰȱ secondary infections. ȱȱƸȱ. 72. ȱ immunity. ȱ. . . . ↑ȱ. . . ŗǯś. . ȱŝŚǰȱřŗ. Not clear. ǰȱ¢. 72. ǰȱĚ ȱ¢¢Dzȱ ǰȱ¢Dzȱǰȱ¢ȱȱDzȱ ǰȱ£¢Ȭȱȱ ¢ǯ Table 7.ȱȱǰȱ¢ȱȱ¢ȱǰȱȱȱ¢ǯ. .
(19) . ,QIHFWLRXV3URFHVVDQG6HSVLV. ÈÉÊËÌÍ ÎÏȱȱȱȱȱ¢ȱȱȱȱ¡ȱȱȱȱǯ ²³ ´µ¶·¸¹ º» ¸²¼²³»¹ ³¶ ³µ» ´·º½»¾³´ ¿³ À²´Á ¿´ ¿Ã »Ä¿¼Å¸»Æ ²³ ²´ ǶÀ³µÇµ²¸» ³¶ ¼¶Ã²³¶À ³µ». ȱȱȱȱȱȱȱȱȱȱȱ ȱȱȱȱȱȱ¢ȱȱȱǯ Śǯřǯȱȱęȱȱȱȱȱȱ¢. ȱ ȱȱ¡ȱȱȱȱȦȱȱ ȱȱȱȱ¢ȱǻǯǯǰȱȱȱȱǰȱȱǼǰȱǯǰȱȱȱȱȱȱ¢ȱȱ ȱDzȱ ǰȱěȱȱęȱȱ ȱ ȱ ȱ ȱ ȱ ȱ ¢ȱ ǰȱ ȱ ȱ ǰȱȱǰȱȱȬȱǰȱȱȂȱȱȱȱȱ¢ȱ¢ǰȱǰȱȱȱȱ ȱȱ ȱ¢ǰȱȱȱȱȱǽ17, 28, 29ǾǯȱȱĴǰȱ ȱȱȱ ȱ ȱȱȱȱȱĚ¢ȱȱȬĚ¢ȱǰȱȱ ȱȱȱȱǰȱ¢ȱȱȱȱ¡ȱȱȱȱȱǽřŖ] ǻȱŘǼǯ. śǯȱȱȱȱ¢ ȱ ȱ ȱ ǰȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ¢ȱ ȱ.
(20) ,PPXQRSDUDO\VLVLQ6HSWLF6KRFN3DWLHQWV KWWSG[GRLRUJLQWHFKRSHQ. ÐÑÒÓÔÕÖ×ØÖÙÔÚ ÖÛÑ ÖÜÒÓ× ÝÑÞÞÕ Ø×Ñ ØßÞÑ ÖÓ ÕÜàà×ÑÕÕ ÙÔ ÒØÔá ÐÙâÑ×ÑÔÖ ãØáÕ ÖÛÑ ÛÓÕÖäÕ ÙÒÒÜÔÑ. ȱȱǯȱ ¢ȱȱȱȱȱȱȱȱǰȱ ȱȱȱȱȱȱȱȱěȱȱ ȱĜȱȱ ǰȱȱ¢ȱȱȱ ȱȱȱȱȱěȱȱȱȱȱȬȱǽ31Ǿǯȱȱȱȱ¡ȱ ȱȬȱȱȬȱȱ ȱȱ ȱȱǽ32Ǿǰȱȱȱ¢ȱȱȱȱ¡ȱȱȱȬȱȱ ȱ ȱȱȱȱȱĴǰȱȱȱȱȱȱȱȱȱ ȱȱ ǽ33ǾȱǻTable 8Ǽǯ. ¢ǰȱȱȱȱȱȱǽ2ǾǰȱȱȬȱȱȱȱȱ ȱȱȱȱȱȱĚȱȱȬȱǰȱ ȱȱȱ ȱȱȱǻ Ǽȱȱǯȱ¢ǰȱȱĴȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱȱ ǻǼȱȱȱȱ ȱȱȱ ȱȱȱȱ¢ȱȱěȱȱ ȱȱDzȱǻǼȱȱȱěȱȱǰȱȱ¢ȱȱȱȱȱȱ ȱȱ ȱȱȱěǰȱȱǻǼȱȱȱȱ ȱȱȬǰȱȱȱDžŜƖȱȱȱ¢ȱȱȱȱȱ¢ȱ¢ȱȱ ¢ȱȱȱȱǽ34Ǿǯ ȱȱȱ ǰȱȱȱȱȱȱȱȱȱȱ ȱęȱǻǼȱȱȱȱȱȱȱȱȱȱǯ. Ȧȱ. Alterations. ȱ. ¢ȱ. ↑ Immature neutrophils. Ȭ. ↑ȱȱȱ. Ȭȱȱ. ↑ȱ¢Ȭȱȱ. ř. ↓ȱ¢ȱ Ȭȱ¡. . ↓ȱ¢ȱ. Ȭŗȱ. ȱ. Ȭȱŗȱ. ↓ Proliferation. ȱŚǰȱ řǰȱ řȱ. Lymphocytes. ↑ Immune checkpoint inhibitors ȱȱ ȱ ↑ȱȱȱ cells ↑ȱȱŗśśȱ¡ ↑ȱ¢ȱ¢ȱ. ↑ȱ ȬŗŖ. Ȭ. ↑ȱ ȱŘ. ȱ. ↑ȱ β. ř . Ȭǰȱ ¢Ȭȱ ¢Ȭȱ Dzȱ řǰȱ Ȭȱ ¢ȱ ȱ řȱ Dzȱ ǰȱ ȱDzȱŗǰȱȱȱȱȱŗDzȱŚǰȱ¢¡ȱȬȱȱŚDzȱ řǰȱȬȱȱ ȱȱřDzȱȱǰȱ¢ȱȱȱȱDzȱ βǰȱȱ ȱȬβDzȱ ǰȱȱŘǯ Table 8.ȱ ȱ ¢ȱȱ¢ȱȱȱǯ. .
(21) . ,QIHFWLRXV3URFHVVDQG6HSVLV. åæçæ èȱęȱ ȱ ȱ ŗşŞŖǰȱ ȱ ȱ ȱ ¡ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱȱȃ¡Ȅȱȱȱȱȱȱȱȱǯ ¢ȱȱȱȱȱȱǻȱǼǰȱȱȱȱȱȱ¡ȱȱ ȱȱȂȱȱĚ ȱȱȱȱȱȱDzȱȱȱ Ĵȱȱǰȱȱȱȱȱȱǯȱȱȱȱȱǰȱȱȱȱ ȱȱȱǻǼȱȱȱȱǻǼȱȱȱǯȱ ȱȱǰȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ǰȱ ȱ ěȱ ȱ ȱ ȱ ¢ȱ ȱ ȱȱȱȱǰȱȱ¢ȱȱȱȱȱ ȱȱȱȱ ǰȱǯǰȱ ȱȱȱĴȱȱȱȱȱȱȱǰȱȱȱȱ ǰȱ ȱ ȱ ǯȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ǯȱ ȱ ȱ ǰȱ ȱ £ȱ ȱ ȱ Ȭǯȱ ȱ ȱȱȱȱȱȱ¢ȱȱȱȱȱǰȱȱȱȱ ȱ¢ǯȱǰȱȱȱȱȱ¢ȱȱȱ¢ȱȱȱȱǰȱ ȱȱȱȬ¢ȱȱȱȱȱȱȱȱȱȱěDzȱǻǼȱ ¢ȱȱȱȱǰȱǰȱǰȱǰȱǯDzȱǻǼȱ¢ȱȱDzȱǰȱȱ¢DzȱȱǻǼȱ¢ȱȱȱȱȱȱȱȬȱȱ ȱ ȱȬĚ¢ȱȱǽ35Ǿǯ śǯŘǯȱ Ȭȱ ěȱ ȱ ȱ ȱ ȱ ȱ ¢ȱ ȱ ȱ ȱ ȱ ȱ ¡ȱ ȱ ǻTable 9Ǽȱ ȱ enhance the depressed immune function in septic and non-septic critically ill patients, includȱǽ36, 37ǾDZ • Ȭγȱǻ ȬγǼȱȱȱ¢ȱȱ¢ȱȱȱȱȱȱȱȱ¢ǯȱ ěȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱȱȱȱ ȱȱ ȱȱȱ Ȭȱ¡Dzȱ ǰȱ¢ȱȱȱȱȱęȱȱȱȱȱȱęȱěȱ ȱȱȱȱȱ ȱǯ • ¢Ȭȱ¢Ȭȱȱǻ ȬǼȱȱȱȱ ȱ ȱ ȱ ȱ ȱ ǯȱ ȱ ȱ ¢ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ¢ȱ ęȱ ěǰȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱȱ ȱȱ ȱȱȱȱ¢ȱȱȱ ȱȱ ȱ Ȭȱ¡ǯ • Ȭŝȱǻ ȬŝǼȱȱȱ¢ȱȱ¢ȱȱ ȱȱ¢ȱȱȱȱ ȱ ȱ ȱ ȱ ěȱ ȱ ȱ ǯȱ ȱ ȱ ȱ ȱ ȱ Ȭ ȱȱȱȱ ȱȱȱȱ¢ȱȱȱȱ ȱěȱȱ¢ǯ • ȱȱȱǻPD1iǼȱȱȱ ȱěȱȱȱȱȱȱ ȱȱȱǰȱ ȱȱȱȱȱȱȱȱȱȱȱǯȱ.
(22) ,PPXQRSDUDO\VLVLQ6HSWLF6KRFN3DWLHQWV KWWSG[GRLRUJLQWHFKRSHQ. . . ě. Pro. . . ȱ. ¢ȱȱȱ demonstrated their Ĝ¢. ȱȬȱ. ¢ȱȱȱ treated. ↓ȱȱȱȱȬ Ě¢ȱ ȱęȱ ȱȱ techniques. ȱ ¢ȱȱȱ demonstrated their Ĝ¢. ȱ. ¢ȱȱ ǻǯǯǰȱ ȱǯȱȱ Ǽ. ¢ȱȱȱ treated ȱȱ ȱ. Not yet . Interferon-γ. Ȭ. IL-7. Immune checkpoint inhibitors. ȱȱ ȱȬĚ¢ȱ mediators. ȱȱȱ and case reports demonstrated its Ĝ¢. Possible septic shock-like ¢ȱĚ¢ȱ reactions. ȱȱȱ ” immune cells. Possible septic shock-like. ȱȱ ȱȬĚ¢ȱ mediators. ”. Possible septic shock-like. ȱ. ”. ¢ȱĚ¢ȱ reactions. ¢ȱĚ¢ȱ reactions ¢ȱȱȱȬ ȱȱě. ȱ ȱȱ. Table 9.ȱȱȱȱȱȱǯ. éêëì íîîïðíñê ëì òóô íì ëõ ëì íëöì õð ëòñïóíìó õêó ëöö÷òó ïóìîðòìó õð õêó ñíòñóï ñóøøì. ȱȱ ȱȱǯȱȱȱȱȱȱǰȱȱȱ ȱ ȱ ȱ ¢ȱ Ȭȱ Ě¢ȱ ȱ ȱ ¢ȱ ȱȱȱȱȱȱȱȃ¢ȱȄDzȱȱȱȱȱȱ ęȱ¢ȱȱ¢ȱȱȱǰȱȱȱȱǰȱȱȱȱȱȱ ȱ ȱ ȱ ȱ ȱ ȱ ¢Ě¢ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱȱȱȱŗȱȱěȱȱǽ38Ǿǯ. 6. Conclusions ¢ȱ ȱ ȱ ǰȱ ȱ ȱ ȱ ȱ ȱ ȱ Ȭȱ DZȱ ȱ ȱ ȱ ȱ £ȱ ¢ȱ ȱ ȱ Ě¢ȱ ȱ ȱ ȱ ȱ. .
(23) . ,QIHFWLRXV3URFHVVDQG6HSVLV. ùú ûüý þÿ û ýýÿ û
(24) û ÿú ùû ý û ÿýû ÿý ûüý ûú. Ȭȱ¢ȱǯȱ ǰȱȱ¢ȱȱȱ¢ȱȱȱȱ ȱ ¢ȱ ¡ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ¢ȱ ȱ ȱ ȱ ȱ ȱ ȱ Ěȱ ȱ ǯȱ ¢ǰȱ ȱ ȱ ȱȱ¢ȱȱȱȱȱĚ¢ȱȱȱȱȱ ȱȱȱȱȱȱȱ¢ȱȱȱȱȱȱǯȱ ȱȱȱ¢ȱȱȱȱȱȱȱȱǰȱȱȱ ȱȱȱȱȱȱȱȱǯ. Author details ȱȘȱȱȱ ȘȱȱȱDZȱȓ ǯ ȱȱȱȱ ȱǰȱ¢ȱȱǰȱĴȱ ǰȱ ǰȱ ¢. ǽŗǾȱ ȱǰȱȱǰȱ¢ȱǰȱȱǯȱȱȱȱȱęȱȱȱȱȱȱǻȬřǼǯȱ
(25) ȱȱȱȱȱǯȱ ŘŖŗŜDz315ǻŞǼDZŞŖŗȬŞŗŖǯȱ DZȱŗŖǯŗŖŖŗȦǯŘŖŗŜǯŖŘŞŝ ǽŘǾȱ ȱ ǰȱ ȱ ǰȱ ££ȱ ǰȱ ȱ ǯȱ ȱ ȱ DZȱ ȱ ȱȱȱȱȱȱȱDZȱŘŖŗŜǯȱ ȱȱǯȱ ŘŖŗŝDz43ǻřǼDZřŖŚȬřŝŝǯȱ DZȱŗŖǯŗŖŖŝȦŖŖŗřŚȬŖŗŝȬŚŜŞřȬŜ ǽřǾȱ ȱ ǯȱ ȱ ȱ ǰȱ ǰȱ ǰȱ ȱ ǯȱ ȱ ȱ ǯȱ ŗşşŜDz24ǻŝǼDZ 1125-1128 ǽŚǾȱ ȱǰȱȱ ǰȱ¢ȱǯȱ ȱȱDZȱȱȱȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ǯȱ ȱ ȱ ȱ ǯȱ ŘŖŗřDz13ǻřǼDZŘŜŖȬŘŜŞǯȱ DZȱŗŖǯŗŖŗŜȦŗŚŝřȬřŖşşǻŗřǼŝŖŖŖŗȬ ǽśǾȱ ȱǰȱȱǰȱȱǰȱȱǯȱ ¢DZȱȱȱ ȱȱȱ ȱȱȱȱǯȱ¢ǯȱŘŖŗŝDz92DZŞřȬşŘǯȱ DZȱŗŖǯŗŖŗŜȦǯ¢ǯŘŖŗŝǯŖŗǯŖŗŘ ǽŜǾȱ ¢ȱ ǰȱ ¢ȱ
(26) ǰȱ Ȭȱ ǯȱ ȱ ȱ ȱ ȱ ȱ ¢ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱ ǯȱ ȱ ȱ ȱ ǯȱŘŖŗŝDz5ǻŘŘǼDZŚŚŝǯȱ DZȱŗŖǯŘŗŖřŝȦǯŘŖŗŝǯŖşǯŘŗ ǽŝǾȱ ȱ ǰȱȱ
(27) ǰȱ ȱǰȱȱǯȱ ȱ¢ȱȱȱȱĚǰȱǰȱȱȱ¢ȱȱȱȱȱ¢ǯȱ ȱȱ ¢ǯȱŘŖŗŞDz9DZśşśǯȱ DZȱŗŖǯřřŞşȦęǯŘŖŗŞǯŖŖśşś.
(28) ,PPXQRSDUDO\VLVLQ6HSWLF6KRFN3DWLHQWV KWWSG[GRLRUJLQWHFKRSHQ. ȱ ǰȱ £ȱ
(29) ǰȱ ȱ ǰȱ ȱ ǯȱ ȱ ȱ ȱ ȱ ȱ ȱ ȱǯȱȱǯȱŘŖŗŚDz9ǻŜǼDZşŞŞŗşǯȱ DZȱŗŖǯŗřŝŗȦǯǯŖŖşŞŞŗş. ǽşǾȱ ĵȱ
(30) ǰȱ¢ȱ
(31) ǰȱ¢ȱǰȱȱǯȱȱȱȱȱȱȱ ȱ ȱȱȱȱȱȱǯȱǯȱŘŖŗŞDz49ǻřǼDZŘŚşȬŘśŞǯȱ DZȱ ŗŖǯŗŖşŝȦ ǯŖŖŖŖŖŖŖŖŖŖŖŖŖşŞŗ ǽŗŖǾȱ ȱ ǰȱ ȱ ȱ ȱ ǰȱ ȱ ǰȱ ȱ ǯȱ ¢ȱ ȱ DZȱȱȱȱǯȱȱ
(32) ȱȱ¢ȱȱȱȱ ǯȱŘŖŗŜDz194ǻśǼDZśśŖȬśśŞǯȱ DZȱŗŖǯŗŗŜŚȦǯŘŖŗŜŖŚȬŖŞŜŘ ǽŗŗǾȱ ȱ
(33) ǰȱ ȱ ǯȱ ȱ ȱ ¢Ȃȱ ȱ ȱ ȱ ǰȱ ȱ ȱ Ȭȱ ǯȱ ȱ ǯȱ ŘŖŗŜDz274ǻŗǼDZřřŖȬřśřǯȱ DZȱ ŗŖǯŗŗŗŗȦ ǯŗŘŚşş ǽŗŘǾȱ ȱǰȱȱ
(34) ǰȱȱǯȱ¢ȱȱDZȱȱȱȱ ȱ ȱ ȯȱ ȱ ǯȱ ȱ ȱ Ěǯȱ ŘŖŗřDZŗŜǯȱ DZȱŗŖǯŗŗśśȦŘŖŗřȦŗŜśşŝŚǯȱȱ ȱŗŜśşŝŚ ǽŗřǾȱ ȱǰȱ ¡ȱǰȱȱǯȱȬȱ¢DZȱǰȱǰȱ ȱȱǯȱȱǯȱŘŖŗśDz81ǻŚǼDZŚŘŜȬŚřş ǽŗŚǾȱ ȱ ǰȱ ȱ ǰȱ ¡ȱ
(35) ǰȱ ȱ ǯȱ ȱ ȱ ȱ ¢Ȭȱ ǯȱȱǯȱŘŖŗŝDz83ǻřǼDZřŖŘȬřŗŚǯȱ DZȱŗŖǯŘřŝřŜȦŖřŝśȬşřşřǯŗŜǯ 11268-4 ǽŗśǾȱ ȱǰȱȱ ǯȱȱȱȱȱȱȱȱȬȱ ǯȱ ȱ ȱ ¢ǯȱ ŘŖŗŞDz14ǻŘǼDZŗŘŗȬŗřŝǯȱ DZȱ ŗŖǯŗŖřŞȦ ǯŘŖŗŝǯŗŜś ǽŗŜǾȱ ȱǰȱ£ £ȱȬǰȱ¢ȱǰȱȱǯȱȱȱȱȱȱDZȱȱ ȱȱȱȱȱȱǯȱȱȱȱ ¢ǯȱŘŖŗřDz25ǻŚǼDZŚŝŝȬŚŞřǯȱ DZȱŗŖǯŗŖŗŜȦǯǯŘŖŗřǯŖśǯŖŖŜ ǽŗŝǾȱ ȱ ȱ ǰȱ ȱ ȱ ǰȱ ȱ ǰȱ ȱ ǯȱ ǰȱ ȱ ǰȱ ȱ Ĵȱ¢ȱȱ¢ȱȱȱȱȱȱȱȱȱ ȱ ǯȱ
(36) ȱ ȱ ȱȱ ȱǯȱ ŘŖŗŜDz315ǻŗŚǼDZŗŚŜşȬŗŚŝşǯȱ DZȱ ŗŖǯŗŖŖŗȦǯŘŖŗŜǯŘŜşŗ ǽŗŞǾȱ ¸ȱ ǰȱ ȱ ǰȱ ȱ ǯȱ ȱ ȱ ¢ȱ ȱ ȱ ǵȱ ȱȱǯȱŘŖŗŜDz42ǻŜǼDZŗŖśŗȬŗŖśŚǯȱ DZȱŗŖǯŗŖŖŝȦŖŖŗřŚȬŖŗśȬŚŗŜŗȬ¢ ǽŗşǾȱ ȱ
(37) ǰȱȱ
(38) ǰȱȱ
(39) ǰȱȱǯȱȱȱ¢ȱȱ¢ȱȬȱ¡ȱȱȱȱȱȱ¢ȱȱȱǯȱȱǯȱŘŖŗŗDz15ǻśǼDZŘŘŖǯȱ DZȱŗŖǯŗŗŞŜȦŗŖŚśŝ ǽŘŖǾȱ ȱ ǰȱ Ĵȱ ǰȱ Ȭ ȱ ǰȱ ȱ ǯȱ Ȭȱ ȱ ȱ ȱ ¢ȱ Ȭ¢ȱ ¢ȱ ȱ DZȱ ȱ ¢ǯȱ ȱ ȱ ǯȱ ŘŖŗŞDz44ǻśǼDZŜŘŝȬŜřśǯȱ DZȱŗŖǯŗŖŖŝȦŖŖŗřŚȬŖŗŞȬśŘŚŝȬŖ. .
(40) . ,QIHFWLRXV3URFHVVDQG6HSVLV. ȱȬǰȱȱ ǰȱȱȬǰȱȱǯȱȱȱȱȱȱ¢-. ȱȱȱȱŘŞȬ¢ȱ¢ȱȱȱǯȱȱǯȱŘŖŗŝDz12ǻŗŖǼDZŖŗŞŝŖŞŞǯȱ DZȱŗŖǯŗřŝŗȦǯǯŖŗŞŝŖŞŞ. ǽŘŘǾȱ ȱ ǰȱ ȱ
(41) ǰȱ ¢ȱ ǰȱ ȱ ǯȱ ȱ ȱ ȱ ȱ ȱ ȱ ǯȱȱǯȱŘŖŗřDz17DZŗŖşǯȱ DZȱŗŖǯŗŗŞŜȦŗŗşŘŘ ǽŘřǾȱ ȱǰȱȱ ǰȱ
(42) ȱ
(43) ǰȱȱǯȱȬȬ¢¢ȱȱȱȱȱȱ ȱ¢Ȭȱȱǯȱȱ
(44) ȱȱ¢ȱǯȱŘŖŗŝDz35ǻŘǼDZŘřŚȬ Řřşǯȱ DZȱŗŖǯŗŖŗŜȦǯǯŘŖŗŜǯŗŖǯŖśś ǽŘŚǾȱ ȱ
(45) ǰȱȱǰȱȱǰȱȱǯȱȱȱ ȱȱȬȬ¢¢ȱȱȱ¢ȱȱȱDZȱȱȱȱ¢ǯȱ ȱǯȱŘŖŗśDz19DZŗřǯȱ DZȱŗŖǯŗŗŞŜȦŗřŖśŚȬŖŗŚȬŖŝřŗȬŜ ǽŘśǾȱ ȱ ǰȱ ȱ ǰȱ ȱ ǰȱ ȱ ǯȱ ȱ ȱ ȱ ȱ ȱ ȱ ǻ Ǽȱ DZȱ ȱ ȱ ȱ ȱ ȱ ȱ Ȭȱ ȱ ¢Ȭ ȱ ȱ ȱ ȱ ȱ ȱ ǻ Ǽȱ ¢ȱ ȱ ǯȱ
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