|
|
|
|
²Ä¥|³¹¡Gµo¯f¤Î§K¬Ì¾Ç
²¤¶
¦b¶g´Á©Êªº¬y¦æ¯f(epidemics)©M¥þ¥@¬Éªº¤j¬y¦æ¯f(pandemics)ªºÃzµo¤¤¡A
¬y¦æ©Ê·P«_¯f¬r¿W¯Sªº¯à¤O¤w²³©Ò©Pª¾¦a¦b¥þ³¡¦~ÄÖ²Õ§O¤¤¡A ´c¦W¬L¹ü¦a¤Þ°_«æ©Êµo¼ö©I§lªº(acute
febrile respiratory)¯e¯f¡C¬y¦æ©Ê·P«_ªº¨âÓ¯S©Ê»¡©ú¤F³\¦h¯f¬r¦b¬y¦æ¯f¾Ç(epidemiological)¤Wªº½¯©µ¡Cº¥ý¬O¦³¯à¤O¦b³¾Ãþ©Î½ÞªºÀxÂéҤº¥X²{©M¶Ç¼½¡C³o¯à¤O¬O¥Ñ°ò¦]«²Õ(genetic
reassortment)©Îª½±µ¶Ç¼½¤Î«á¦b¤£³W«hªº¶¡¹j¤¤¶Ç¼½¨ì¤HÃþ¡C¨ä¦¸¬O·í¯f¬r¤w¦b¤HÃþ½T¥ß«á«á¡A
¨º¨³³t©M¤£¥i¹w®Æ¤Î«n§K¬Ì¥Ø¼Ðªº§Üì(antigenic)ÂàÅÜ¡C
¤@Ó¯à¤Þ°_¤j¶qµo¯f²v(morbidity)¡A ¸û¤jªº±wªÌ¦º¤`²v¤Î°ª±µÄ²¶Ç¬V©Êªº¯f¬r¬O¤@Ó쫬ªºµJ¼{(archetypal
anxiety)¡C¬y¦æ©Ê·P«_¦³¼ç¤O¥h²£¥Í³o¼Ëªº¤@Ó§½±¡C³Ì¦¦Û¤Q¤»¥@¬ö¡A ¨¬°¤Þ°_¤HÃþ¯e¯f°_¦]ªº¬y¦æ©Ê·P«_¯f¬r¤w¸g¶Ç¼½¦b¤HÃþ±Ú¸s·í¤¤(Cox
& Kawaoka 1998)¡A ¾ÉP¨C¤@¦Ü¤T¦~ªº¶g´Á¬y¦æ©Êµo¼ö©I§lªº¯e¯f¡C¦¹¥~¡A ¦]¬°¤@Ó·s¯f¬r¦b¤@Ó¨S¦³§K¬Ì¤OªºÁ`±Ú¸s¤¤¥X²{¡A
©Ò¥H¨C¤@Ó¥@¬ö³£¸g¾ú¨ì¤@¨Ç¥þ°ê¬y¦æ¤Î¯à¨³³t¦a±²¦Ü¥þ¥@¬Éªº¯e¯f¡C¥þ°ê¬y¦æ¯e¯fªº¯S¼x¥]¬A³q±`¦b©u¸`¤§¥~¥X²{¡A
·¥«×¨³³tªº¶Ç¬V¨Ã¦b¦a²yªº¤£¦P¦a¤è¦P®ÉÃzµo¡A ©M¦b©Ò¦³¦~ÄÖ²Õ¤¤³£¦³°ª§ðÀ»²v¡A ¬Æ¦Ü³s°·±d¦~»´¦¨¤H³£¦³°ª¦º¤`²v¡C¦Ò¼{¨ì¥@¬É¤H¤f¡A
°ê»Ú®È¦æ©M®È¹C·~ªº¼Wªø«á¡A¥þ°ê©Ê¬y¦æ©Ê·P«_¹GªñªºÃzµo¬Æ¦Ü±o¨ì¤@ӧ󨳳t¶Ç¼½ªº¼ç¤O¡C¬°¤F§ó¥þ±¦aÁA¸Ñ³oÓ¥þ²y¬y¦æ©Ê«Â¯ÙªºI´º¡A
³oÓ³¹¸`±N·|´yz¯e¯fªºµo¯f(pathogenesis)ì²z©M¯f¬r»P§K¬Ì¨t²Î¤§¶¡ªºÄvÁÉ¡C
µo¯f
¬y¦æ©Ê·P«_¯f¬rªºP¯f©Ê(pathogenicity)©M¬r©Ê¬O¥Ñ´XÓ¤¬¬Û¼vÅTªº¦]¯À©Ò¨M©w:
¥Ò) ±J¥D¦]¯À:
- ¥Ø¼Ð·P¨ü¾¹¦b±J¥D²ÓM¤Wªº¦s¦b
- »Ã¯À¦b±J¥D²ÓM¸Ìªº¥i¥Î©Ê¬O¦b¯f¬rªº¶i¤J©M½Æ»s¤¤¤£¥i¯Êªº
- Ó§O±J¥D§K¬Ì¤O(immunocompetence)ªºª¬ºA
- ¯S²§©Ê§K¬Ì(Specific immunity)¦bÓ§O±J¥D¤Î¥Ø¼Ð±Ú¸s¤º¹ï¥I¬Y¯f¬r§ÜÅé¿ëÃѪº°Ï°ì(epitopes)
- §K¬Ì¨t²Î¥Ñµoª¢¨Ï¦³®Ä¦a±±¨î¯f¬r½Æ»s¦Ó¨S¦³¹ï±J¥D³y¦¨ÄY«ªþ±a·l¶Ëªº¯à¤O
¤A) ¯f¬r¦]¯À:
- ¹ï±J¥D²ÓMªºµ²¦X¯à¤O
- ¯f¬r´²¼½ªº¯à¤O (virus shedding)
- ²ÓM¯f²zÅܤÆ(cytopathogenic effects)ªº¨î®e³\¯f¬r½Æ»s©M¥Ñ±J¥D±±¨î¤§¶¡¡A
¦³¤@Ó¦X¾Aªº¥¿Å
- §K¬Ì¤ÏÀ³ªº¦³¿ï¾Ü©ÊÀ£¤OÅX°Ê§ÜìÅܲ§ªººtÅÜ¡A ¨Ï¯à¥Ñ§K¬ÌºÊ±±¨t²Î(immunosurveillance)¤¤°k²æ
- ±q¤H¯b¦@¥Í¶Ç¬V¯f(zoonotic disease)¦Ó¨Ó¤£¦Pªº¯f¬r«~ºØ(strains)»Pµ²¦X¡A
¨Ï¥Ñ§K¬ÌºÊ±±¨t²Î¤¤°k²æ
- §K¬Ì¤ÏÀ³ªº½Õ¾ã´î®z(attenuate)¦³®Äªº±J¥D¨¾¿m¾÷¨î
¯f¬rªº«I¤J: ¯f¬r«ç»ò¶i¤J±J¥D?
¬y¦æ©Ê·P«_³Q¶Ç°eªº¥Dn¤è¦¡¬O³z¹L¯B½è(aerosols) ©M¤pºw(droplets)¡A
±q¤H¶Ç¨ì¤H¡C¬y¦æ©Ê·P«_µM«á³q¹L©I§l¹D¶i¤J±J¥D¡C¤@Ó¤HªºªÍ³¡¦³¤j¬ù¤T»õӲ׺ݪwÅn(terminal
sacs)¡A ¥s°µªÍªw(alveoli)¡A¦b³Q§lªºªÅ®ð©M¦å²G¤§¶¡ªº®ðÅ饿´«¤¤°_¨ä§@¥Î¡C¤HªÍ³¡ªºÁ`§l¦¬©Ê°Ï°ì½d³ò±q80¨ì120
m2¡C¤HªºÀR®§´«®ð²v(resting ventilation rate)¬O¤j¬ù¨C¤ÀÄÁ6
¤½¤ÉªÅ®ð¡A ¤Þ¤J¤j¶q¥~¨Ó·L²É©MªÅ®ð¤¤ªº¸ªj¥]§t¥i¼ç¦bªº¯f¬r¨ìªÍ³¡¡C·L²Éªº¨H¾ý¨ú¨M©ó¥¦Ìªº¤j¤p:
«D±`¤pªºÁû²Éªº§l¤J¤£¾ÉP³q¹L¤pºÛ©Î¤ä®ðºÞ¨t²Îªº§l¦¬¡Cª½®|¤j¬ù1 ¨ì4 £gmªº¤p¤pºw·|¨I¾ý¦b¤p®ð¹D¡C¸û¤jªº·L²É¤£¯à¶i¤J©I§l¨t²Î©Î³Q¨H¾ý¦b¤W©I§l¹D(¹Ï1A)
¡C
²³¦hªº±J¥D¨¾¿m¾÷¨î¥]¬A¾÷±ñ»ÙêªýÄd©I§l¹D¨ü¨ì¶Ç¬V¡C©I§l¹D³Q¥ÎÂH½¤ÅÖ¤òªº¼h¥]¬AÅÖ¤ò²ÓM(ciliated
cells)¡A ÂH²G¤Àªc²ÓM(mucus-secreting cells)©M¸¢(glands)©ÒÂл\(¹Ï1
B) ¡C¥~¨Ó·L²É¦b»ó¬}©Î¤W©I§l¹D³QÂH²G(mucus)©Ò§x¡A ¹B¦^¨ì³ïÀY¤Î§]¤U¡C¥~¨Ó·L²É±q¸û§Cªº©I§l¹D³Q¤W¥Ö²ÓM(epithelial
cells)ªºÅÖ¤ò¦æ°Ê´£¤W¡C¦b¯Ê¥FÅÖ¤ò©ÎÂH²GªºªÍªw¤U¡A ¥Ñ¥¨¾½²ÓM(macrophages)t³d·´Ãa·L²É(¹Ï1)
¡C
¹ï±J¥D²ÓMªºµ²¦X(Binding)
¬y¦æ©Ê·P«_¯f¬rªº¥Dn¥Ø¼Ð¬O©I§l¹Dªº¬Wª¬¤W¥Ö²ÓM¡C¦pªG¯f¬r·P¨ü¾¹¬O¦s¦b©M¤u§@ªº¡A
³o¨Ç¤W¥Ö²ÓM¤]³\¬O©ö¨ü¶Ç¬Vªº¡C¦]¦Ó¡A ¯f¬r·P¨ü¾¹¬O¦³¨M©w©Êªº©Ê¦V(tropism)¡C¦ý¬O¡A
³oÓ²¤Æªº¼Ò«¬¸g±`¬O¤£¨¬¥H¸ÑÄÀ¯f¬r©}©Ê¡A ¦]¬°·P¨ü¾¹¦b±J¥Dªº¤À§G¤@¯ë¤ñ¤wÆ[¹îªº¯f¬r¦V©Ê¤À§G¬°¼s¡C

¹Ï1 . ¬y¦æ©Ê·P«_¦b©I§l¹D¶i¤Jªº¦aÂI¡C
(A) Åã¥Ü¤HÃþ®ð¹Dªº¸Ñå©M¥\¯àºc³y¡C¬y¦æ©Ê·P«_º¥ý¶Ç¬V¤W®ð¹D©M¦b¤ä®ðºÞ(bronchus)©M²Ó¤ä®ðºÞªº(bronchioli)ÅÖ¤ò²ÓM¡C¤Þ°_ªºÁ{§Éºî¦X¯gª¬¥]¬A®ðºÞª¢(tracheitis)¡B¤ä®ðºÞª¢(bronchitis)¡B²Ó¤ä®ðºÞª¢(bronchiolitis)¡A
©M¤ä®ðºÞªÍª¢ (bronchopneumonia)¡C¯à¾AÀ³ªº§K¬Ì¤ÏÀ³¥Ñ²O¤Úµ²ªu®ð¹D¶}©l¡C(B)
©I§l¤W¥Ö¥Ñ¤@¼hÂH²G(¤ä®ðºÞ)¡A ÅÖ¤ò²ÓM(¤ä®ðºÞ©M²Ó¤ä®ðºÞ)¡A ©MªÍªwªº¥¨¾½²ÓM(ªÍªw)¤Wªº¯S§O¸Ë³Æ«O½Ã±µ¿æ¦Ó¨Óªº¯fì¥Íª«¡C
¦b¬y¦æ©Ê·P«_ªº¶Ç¬V¤W¡A ¯f¬r¦å²y¾®¶°¯À(hemagglutinin)(HA)
·P¨ü¾¹³s±µ¦ì¸m¥²»Ý³s±µ¨ì±J¥D²ÓMªºªí±³s±µ¦bÖº¾T(sialic acid)¼h¤Wªº»Ä¥b¨Å¿}
(galactose)(Weis 1988) ¡CHA³s±µ¦ì¸mªº¬Y¨Ç°Ï°ì¦b¬y¦æ©Ê·P«_¯f¬r¨È«¬¤§¶¡¬O°ª«×³Q«O¦uªº(Daniels
1984)¡C±J¥D¥i¯à¥i¥H¥Ñ´XÓ¾÷¨î¨¾¤î³s±µ:
(1) ¯S²§©Ê§K¬Ì¤ÏÀ³(specific immune response)©M¯S²§©ÊIgA
§ÜÅ骺¤Àªcª«¡A (2) «D¯S²§©Êªº¾÷¨î(unspecific mechanisms)¡A
Ä´¦pÂH½¤ÅÖ¤ò(mucociliary)ªº²M°£©ÎÂH³J¥Õ(mucoproteins)ªº¥Í²£¯à³s±µ¨ì¯f¬r¦å²y¾®¶°¯À¡A
¤Î(3) ±J¥D·P¨ü¾¹(Öº¾T¼h»Ä)ªº°ò¦]¦h¼Ë¤Æ¡A °ª«×³Q«O¦s¦b¦P¼ËªººØÃþ¡A ¦ý¤£¦P¦b³¾©M¤Hªº·P¨ü¾¹¤§¶¡(Matrosovich
2000)¡C µ²ªG¡A ³¾¯f¬r»Ýn¦b¦å²y¾®¶°¯À·P¨ü¾¹³s±µªº¦ì¸m¶i¦æ¬ðÅÜ¡A ¥h³q¹L³¾©M¤H¤§¶¡¸ó¶V±J¥Dªº»Ùê¡C¦b½Þ°¦¨¤W¡A
Öº¾T¼h»ÄºØÃþ¦h§Î©Ê(polymorphisms) ©M¹ï¤H¨Ã³¾ªº¥b¨Å¿}¦b²Õ´¤Wªº³s¦X³Q¦@ªí¹F(co-expressed)¡C©Ò¥H¡A
¦@¶Ç¬V¨Ã³¾©M¤Hªº¬y¦æ©Ê·P«_¥i¯àµo¥Í¦b½Þ©M¯à®e³\³¾¨Ã¤HºØ¦b¦@³Q¶Ç¬Vªº(co-infected)²ÓM§Üì¯S©Êªº°ò¦]«²Õ¡C³Ìªñ¡A
¦³Åã¥Ü¬Y¨Ç³¾¬y¦æ©Ê·P«_¯f¬r¦b¤H©M³¾¤W¯à³s±µ¨ì¤£¦Pªº¥Ø¼Ð²ÓM(Matrosovich 2004)
¡C³o¯à¸ÑÄÀ±q90 ¦~¥Nªºµ²§À¥H³¾¬y¦æ©Ê·P«_±q¸V¯bª½±µ¦a¶Ç¬V¨ì¤Hªº´XÓ®×¥óªºÆ[¹î¡CH5N1
©M¤@¨Ç¨ä¥L¨È«¬(subtypes)¬y¦æ©Ê·P«_A ¯f¬r¯à³s±µ¨ì¦b¤H²´¤Wªº·P¨ü¾¹ (Olofson
2005) ¡C
©M¬y¦æ©Ê·P«_¯f¬rªº³s±µ¤@¼Ë«nªº¬O±q¥¦¦b±H¥D²ÓM¤W³s±µ¦ì¸mªº¤Á³Î(Cleavage)¡C¤Á³Î¬O¯f¬r¯«¸gÓi»ÄžJ»Ã¯À(neuraminidase)ªº¥\¯à¨¤¦â(Chen
1998)¡C¬y¦æ©Ê·P«_¯f¬rªº¬r©Ê(virulence)¨ú¨M©ó¯«¸gÓi»ÄžJ»Ã¯À»P¦å²y¾®¶°¯ÀªºÝ®e©Ê¡C¤@Ó¤w¸g¦b¦å²y¾®¶°¯À¶i¦æ¬ðÅÜ(mutations)ªº¼@¬r¯f¬r»Ýn¦b¯«¸gÓi»ÄžJ»Ã¯À¶i¦æ¬ðÅÜ¥H«O«ù¨ä¬r©Ê(Baigent
& McCauley 2003¡A Hulse 2004)¡C µ²ªG¡A µo²{¹ï¯«¸gÓi»ÄžJ»Ã¯À§Ü¤Æ¾¯(inhibitors)ªº¦³§ÜÃĩʪº¬y¦æ©Ê·P«_¯f¬rªº¾AÀ³¤O©M¬r©Ê¬O´î¤Ö¤Fªº(Yen
2005)¡C
·í²ÓM½¤©M¯f¬r¥Ñ¯f¬r·P¨üÅé¤w³Q±µªñ¦a¨Ã¦C(juxtaposed)¡A
½Æ¦XÅé¬O³Q²ÓM½¤¤º§](endocytosed.)¡CH+ Â÷¤l¶i¤J«áMÄá¤pM(late endocytic
vesicles)§@¬°¤@¦¸¥Í²z¾Ç¨Æ¥ó¡A µM«á»Ä¤Æ(acidification)¤º³¡¡C¦b»Ä¤Æ¤¤¡A
¯f¬rHA ¶i¦æ¤@ӧκAªº«·s¾ã²z¥H¥Í²£¿Ä¦X¬¡ÅD³J¥Õ(fusiogenic protein)¡CHA
ªºÀôª¬°Ï°ì(loop)¦¨¬°±²¦¨°éªº¨÷³Ì²×±a¨Ó¯f¬r©MMÄá¤pM½¤ªº§ó¥[±µªñ¥H«K¿Ä¦X¥i¥Hµo¥Í¡C¤¹³\¯f¬r®Ö¿}®Ö»ÄªºÄÀ©ñ¨ì²ÓM½è¤º¡A
¨Ï¦b»Ä©ÊMÄá¤pM¤ºªºH+ Â÷¤l ¥ÑM2 Â÷¤l´ë¹D¬¦¤J¯f¬r¤º³¡¡Cµ²ªG¡A ¦b¯f¬r©MMÄá¤pM½¤
ªº¿Ä¦X¤§«á¡A ¦]¥Ë¸Ñ¦bM1 ©M®Ö¿}®Ö³J¥Õ½è½Æ¦XÅé(ribonuclein complex)¤§¶¡¹ï§C»ÄÆP«×±Ó·P
ªº¬Û¤¬§@¥Î¡A ¯f¬r®Ö¿}®Ö»Ä±qM1¤À¶}¡C¯f¬r®Ö¿}®Ö»ÄµM«á¥H¸¢¤TÁC(ATP)¨Ì¿à¤è¦¡³Q¿é¤J²ÓM®Ö¶i¦æÂà¿ý(transcription)©MÂàͧ@¥Î(translation)(Flint
2004)¡C

¹Ï2: ¬y¦æ©Ê·P«_A ¯f¬rªº½Æ»s¶g´Á¡C ¯f¬rªº³s±µ©M«I¤J¡A¥HMÄá¤pM½¤¿Ä¦X©M¯f¬r®Ö¿}®Ö»ÄªºÄÀ©ñ¡A
¦b²ÓM®Ö¤ºªº½Æ»s¡A µ²ºc©M«Ê®M³J¥Õ(envelope proteins)ªº¦X¦¨¡A ¯f¬rµoªÞ©MÄÀ©ñ¯à¶Ç¬V¾F©~ªº¤W¥Ö²ÓM
(±qCox & Kawaoka 1997§ï¨}ªº)¡C
ºnªº½Æ»s¦b¨º¸Ìµo¥Í?
²ÓM³J¥Õ»Ã¯À(proteases)¥²»Ý¸g±`¤Á³Î¯f¬r³J¥Õ½è§Î¦¨¦¨¼ô¦Ó´I¶Ç¬V©Êªº¯f¬r·L²É¡C¦]¦Ó¡A
¥t¥~¥i¶i¤J·P¨ü¾¹ªº¦]¯À¥i¨M©w¯f¬r½Æ»sªº¦ì¸m¡C¦b¤HÃþ¤è±¡A ¬y¦æ©Ê·P«_¯f¬r½Æ»s¤@¯ë¨ü©ó©I§l¹D¤W©M¤U³¡ªº¤W¥Ö²ÓM¡C³o¬O¥Ñ©óµ·®ò»Ä(serine)³J¥Õ»Ã¯À¡A
¯Ø³J¥Õ§J©Ô(tryptase Clara)¡A ¦³ªºªí¥Ü¡A ¥Ñ«DÅÖ¤ò¤ä®ðºÞ¤W¥Öªº§J©Ô²ÓM©Ò¤Àªc¡C³Q²b¤Æªº»Ã¯À¤Á³Î²ÓM¥~·L²É¤¤ªº¦hÐ`¤ÓÃìHA
Ã쪺«eÅéHA0©M¬¡¤Æ¯f¬r¤ºªºHA ¥O¥L̨ü·P¬V¡C¤@¨Ç°ª«×¼@¬r©Ê³¾Ãþ¬y¦æ©Ê·P«_ªº«~ºØ¡A µM¦Ó¡A
¥]§t¦bHA ¥i³Q¤Á³Îªº¦ì¸mªº°ò¦]´¡¤J¾ÉP¸g´¶¹M¦s¦b³J¥Õ»Ã¯À(ubiquitous protease)³B²z¡C³o¤]³\¾ÉP¤w×§ï¹Lªº¦V©Ê¤Î¡A¥t¥~½Æ»sªº¦ì¸m¦b°Êª«©M¤H¤§¤º(Gamblin
2004 ) ¡C¦b¤H¨¤Wªº³¾Ãþ¬y¦æ©Ê·P«_²Õ´©}©Ê(H5N1)¨S¦³¤@Ó¦X¾Aªº©w¸q¡C¦b¤@Ӯץ󤤡A
¯f¬r®Ö¿}®Ö»Ä¥Ñ¤@Ó¤ÏÂà¿ý»E¦X×QÃì¤ÏÀ³¤¤¡A ³QÀË¥X¦s¦b©óªÍ¡B¸z©MµÊŦ¡A ¦ý¶§©ÊÃì(positive-stranded)
¯f¬r®Ö¿}®Ö»Ä¡A ªí©ú¯f¬r½Æ»s¡A ¤w§¹¥þ¨î©óªÍ©M¸z¤º(Uiprasertkul 2005)
¡C¦]¦Ó¡A ¦b¤H¤ºªºH5N1¯f¬r½Æ»s¤]³\³Q©ó©I§l¹D©M¤p¸z¹D¤£¦P©ó¦b¨ä¥¦÷¨Å°Êª«©M³¾Ãþ¤¤¤w³QÃÒ©úªº´²¼½©Ê(disseminated)¶Ç¬V¡C
¶Ç¬V¯f«ç¼Ë¦b±J¥D¶Ç¼½?
¤@¥¹¬y¦æ©Ê·P«_¤w°ª®Ä²v¦a¶Ç¬V©I§l¤W¥Ö²ÓM¡A ¦b´X¤p®É¤§¤º¡A
½Æ»s«K·|²£¥Í³\¦h¯f¬r¡C¶Ç¬V©Êªº²É¤l±q¤W¥Ö²ÓMªº²ÓM½¤³»ºÝÀu¥ý¦a³QÄÀ©ñ¨ìªÍ®ð¹D¡A ³oÓ¹Lµ{¥sµoªÞ(budding)¡C¦]¾F©~²ÓMªº¨³³t¶Ç¬V¡A
³o¦³§Q©ó¯f¬r¦bªÍ¤ºªº§Ö³t¶Ç¼½¡C ¥Ñ¦ÛµMµo¥Íªº¬ðÅÜÅé¦bHA¤Á³Î¦ì¸mªº§ïÅÜ¡A ³o¯àÅãµÛ¦a¼vÅT¬y¦æ©Ê·P«_ªº¦V©Ê©MP¯f©Ê¡Cµ²ªG¡A
¥¦¥i¥H¥Ñ¨ä¥¦²ÓMªº³J¥Õ»Ã¯À©ÒÃѧO¡C
³o¸ÑÄÀ¨ì¬°¤°»ò¦b»´ä³\¦h³Q·P¬V³¾Ãþ¬y¦æ©Ê·P«_(H5N1)ªº¤H¡A
¦³¹¹D(gastrointestinal)¡B¨x©MµÇŦ¡A ©M©I§lªº¯gª¬©M¬°¤°»ò³o¨Ç±wªÌªº¯f¬r·|¹ï¦Ñ¹«²£¥Í¯«¸g¼@¬r(neurovirulent)
(Park 2002). ³o¨Ç¯gª¬¬O§_°_¦]¦åì¶Ç¼½(hematogenic spread)©Î¤Ï¬M¯f«DªÍ(non-pulmonal)§Î¦¡ªº¯f¬r¶i¤J¨ì±J¥D¤´µM¬O¤£©ú®Ôªº¡C¦ý¬O¡A¦bNA
¸ÌªºÅܤƤ]¥i¯à¡A ¦³¤@³¡¤À¡A ¸ÑÄÀ¬y¦æ©Ê·P«_ªºµo¥Í¦b³\¦h²Õ´¤Wªº(pantropic)¥»½è¡C¨Ò¦p¡A
¨ú¦Û¹êÅç«Ç¬y¦æ©Ê·P«_ªºWSN/33«~ºØ¡A ²Ä¤@Ó³Q¤ÀÂ÷ªº¤HÃþ¬y¦æ©Ê·P«_¯f¬rªºÅÜÅé¡A ¤£¦P©ó¦h¼Æ¤HÃþ¬y¦æ©Ê·P«_«~ºØ¡A
¯à¦b¸ÕºÞ¤º¦b¨S¦³¥[¥H¯Ø³J¥Õ¦Ó½Æ»s¡C¦b³o¯f¬r¡A ¤@Ó½X¤ºªº§R°£(in-frame deletion)¥h°£¦bNA´Ý°ò46
(residue 46) ¤WªºÁÞ¤Æ(glycosylation)¦ì¸m¤¹³\¯«¸gÓi»ÄžJ»Ã¯À³s±µ©M¹jÂ÷M¼ß¯Àì(plasminogen)¡C³o¾ÉP¦a¤è©Ê´¶¹M¦s¦bªº³J¥Õ»Ã¯À«eÅéÅܦ¨°ª¿@«×¡A¥OHAªº¤Á³Î¼W¥[¡C³o¨Ç¬ã¨sµ²ªG´£¥X¤@Ó¬°¤°»ò¬y¦æ©Ê·P«_A
¯f¬r©Î³\¨ä¥¦¯f¬r¦b¤HÃþ¯àÅܱo°ª«×P¯f©Êªº¤è¦¡¡C(Goto & Kawaoka 1998)
¡C¦³½ìªº¬O¡A °ò¦]««Øªº1918¦~¥þ°ê¬y¦æªº¦è¯Z¤ú¬y¦æ©Ê·P«_¯f¬r(H1N1) ªº¬ã¨s ÅãÅS¤FNA
¶Ç¹FªºHA¥i¤Á©Êªº¥t¥~¾÷¨î¥i¯à»P¨º¯f¬r½Æ»s©M¨ä¬r©Ê¬ÛÃö (Tumpey 2005) ¡C
²×©ó¡A °Êª«¬ã¨sÅã¥Ü¡A ±µºØªº³¡¦ì(site of inoculation)¥i¨M©w¬y¦æ©Ê·P«_¯f¬rªº¦b±J¥Dªº¶Ç¼½¸ô½u¡C¨Ò¦p¡A
¶Ý¤¤©Ê¥Õ¦å²y©Ê (neutrotropic) NWS«~ºØ¸g¸¡½¤¤º³q¹L¦åì (hematogenous)¶Ç¼½´²¼½¨ì¸£³¡¡A
¦ý·í¯f¬r³Q±µºØ¦b»ó¤l¤º¡A ¥¦Ì¯à³q¹Lª¾Ä±¯«¸g¤¸(sensory neurons) ¨ì¹F¤¤¥¡¯«¸g¨t²Î(central
nervous system) (Flint 2004). «áªÌ¡A ¦b»´äH5N1 ¯f¬r¤¤¤w³Qµý¹ê(Park
2002)¡C
±J¥D³Ìªìªº¤ÏÀ³¬O¤°»ò?
ÁöµM¤@ºØ®É±`µo¥Íªº¯e¯f¡A ±M¤@©Êª¢¯g©Ê¼Ò¦¡(specific
inflammatory patterns) ©Î§K¬Ì¤ÏÀ³½Õ¸`¤Î¦b¤HÃþ¬y¦æ©Ê·P«_¤¤¡A²ÓM¯fÅܪºµo¯fì²z¬O¨Ã¥¼§¹¥þ³QÁA¸Ñ¡C
³¾¬y¦æ©Ê·P«_¬O¤@ºØ´²¼½©Ê¯e¯fªº³ø§i¡A¦h¬O¨Ó¦Û°Êª«¬ã¨sªºÃÒ¾Ú¡CµM¦Ó¡A³o¼Ëªº¯f²z¥Í²z¾Ç¼Ò«¬¤]³\¦b¤H¨¤W¥þµM¤£¦P¡C
²ÓM¿E¯À(cytokines) ©M¼ö¯f
¤@Ó¥Dn°ÝÃD¬O°ò¥»¤W¦b©I§l¹D¤@ºØ¦a¤è¤Æªº¶Ç¬V¬O«ç¼Ë¥i¾ÉP³o¼ËÄY«Åé½è¤Wªº¯gª¬(constitutional
symptoms)¡C ¦b³\¦h¨ä¥¦¶Ç¬V¯f¤¤¡A «D±M¤@©Ê¤Î¦³¾AÀ³¤Oªº§K¬Ì¤ÏÀ³¹ï¬y¦æ©Ê·P«_ªºÁ{§É¯gÔ(signs)©M¯gª¬¤Î¶Ç¬V«áªº±±¨î¨ã¬Û·í¤jªº°^Äm¡C³o¨Ç§K¬Ì¾÷¨î¥i¾ÉP¦a¤è©Ê¨Ã¨t²Î©Êªº§@¥Î¡C¯S§O¬O¦b§K¬Ì¨t²Î¤§¤º¡A
¦b¶Ç¬V¥H«á¡A ¥Ñ©I§lÂH½¤¤W¥Ö©M§K¬Ì²ÓM¨³³t¦a³Q²£¥Íªº²ÓM¿E¯À¡A ¬O¿E¬¡²ÓM¦a¤è©Êªº¿E¯À¡A¡CÁͤƿE¯À(chemokines)¬O§@¬°¬°§K¬Ì¨t²Î²ÓMªºÅX¤Æª«½è(chemoattractants)¬O²ÓM¿E¯Àªº¤@Ó¤l¶°(subset).
¨Ò¦p¡A ¬y¦æ©Ê·P«_¶Ç¬V¦b¤HªºÃþ¼ß²ÓM«¬(plasmacytoid)©M°©Åè¾ðª¬²ÓM(myeloid
dendritic cells) »¤¾É¤@ÓÁͤƿE¯À¤Àªcª«µ{§Ç®e³\¤£¦Pªº§K¬Ì¨ü°Ê¾¹(effector)³Q¨ó½Õ¦a§l¤Þ(Piqueras
2005¡A Schmitz 2005)¡C ³Ì«nªº²ÓM¿E¯À¬°¤º¦]©ÊP¼öª«(endogenous
pyrogens)©M³Q¤¶¤J¦b¼ö¯fªºµo¯fì²z¤§¤¤: IL-1Α/Β¡A
TNF Α/Β¡A IL-6¡A¤zÂZ¯À(interferon)(IFN)
Α/γ¡A IL-8¡A ©M¥¨¾½²ÓMª¢©Ê³J¥Õ(macrophage
inflammatory protein)(MIP)-1Α¡C
³o¨Ç²ÓM¿E¯À¦û¤@¤j³¡¥÷¦b¸g¹êÅç©Ê©Î¦ÛµM©Ê¥H·P¬V¬y¦æ©Ê·P«_ªº¤HÃþªº»ó«|¬~º°¤¤³Q¬d¥X
(Brydon 2005) ¡C¦³´£Ä³«ü³o¨Ç§½³¡©Ê©Î¨t²Î©Ê³Q¥Í²£ªº²ÓM¿E¯À¡A ±µµÛ¥~¦]©ÊP¼öª«(exogenous
pyrogens) (¦p¬y¦æ©Ê·P«_) »P§]¾½²ÓMªº¬Û¤¬§@¥Î¡A ¨ì¹F¤¤¥¡¯«¸g¨t²Î¡C¦b¤U¥C¸£¡A
¦³¤@¤p½d³ò¡A ºÙ¦åºÞ¯ßÂO²×ºÝ¾¹©x(Organum vasculosum laminae
terminalis)¡A ¨ä¤º¦³¤@Ó³Q´î¤Öªº¦å¸£ »Ù¾À(Blood-Brain-Barrier)©M¤¹³\P¼öª«³q¹L¡C¦b³oÓ¦ì¸m¡A
¥H¨Ì¿à¾¯¶q(dose-dependent)¤è¦¡¡A ¥LÌ»¤¾É«e¦C¸¢¯À(prostaglandins)
¡A ¯S§O¬O«e¦C¸¢¯ÀE2 ªº¥Í²£¡C³o¨Ç¶Ç»¼ªÌ(mediators)¼W¥[«í·Å¾®©TÂI(thermostatic
set point)©MIJµo½ÆÂøÅé·Å½Õ¸`¾÷¨î(thermoregulatory mechanisms)¼W¶qÅé·Å¡C¹ê»Ú¤W¡A¦b¥H¤W³Q´£¤Îªº²ÓM¿E¯À»P¬y¦æ©Ê·P«_¶Ç¬VªºÄY«©Ê¨Ã¨S¦³³QÃöÁp¡A
ª§½×¶É¦V©ó¥¦Ìªº°ò¦]¦h®Ä©Ê(pleiotropy)©M¦b«H¸¹¦æ®|¤§¤¤ªº¤¬¬Û¤zÂZ¡C²ÓM¿E¯Àªº¬ÛÃö©Ê¤]³\¦b¬y¦æ©Ê·P«_«~ºØ©ÎÓÅ餧¶¡³£¦³¤£¦Pªº¦a¤è¡C¬y¦æ©Ê·P«_¶Ç¬V¥H»´ä1997¦~ªºH5N1
«~ºØ³Q´£Ä³¦³®Ä¦a»¤¾É¦ÛNS°ò¦]²£ª«ªº«eµoª¢(pro-inflammatory)²ÓM¿E¯À(¯S§O¬OTNFΑ)
(Cheung 2002¡A Lipatov 2005¡A Chan 2005). ¬ã¨s¥Øªº¬O¦b©ó¿ë»{¨ä¥L»¤¾É²ÓM¿E¯ÀÄÀ©ñªº¯f¬r²Õ¥óÅã¥Ü:¤£½×±q³Q¶Ç¬Vªº¦Ñ¹«ªºªÍ¡A
©Î¬O±q¬y¦æ©Ê·P«_¯f¬r¦X¦¨¤¤¨ú±oªºÂùÃì(double-stranded) (ds) ®Ö¿}®Ö»Ä·íª`®g¤J¦Ñ¹«CNS
¤ß«Ç®É¡A ¬Oµo¼ö©Êªº¡C·í¥¦Ì¦º«á¡A ³o¼ËªºdsRNA ±q³Q¶Ç¬Vªº²ÓM³QÄÀ©ñÄ~¦Ó¨ë¿E²ÓM¿E¯À¥Í²£¡C³Ìªñ¬ã¨sÅã¥Ü¡A
ÂùÃì·PÀ³§âÃö¨üÅé(dsRNA-sensing Toll-like receptor) (TLR)
3³Qªí¹F¦bªÍ¤W¥Ö²ÓM ¨ÃTLR3 ª½±µ°Ñ»P¹ï©I§l¤W¥Ö²ÓMªº§K¬Ì¤ÏÀ³ (Guillot 2005¡A
Akira & Takeda 2004)¡C¦³½ìªº¬O¡A¤@Ó¤HÃþ»P¥ÍѨӹï§Ü¬y¦æ©Ê·P«_§K¬Ì¤ÏÀ³ªº¶}©l¡A
¬Û¤ñ¥ÑTLR 3¬d¥XdsDNA¡A ¨ú¨M©Ê¤£¨È©ó³q¹LTLR 8ªº¿ë§O³æÃì®Ö¿}®Ö»Ä(single
stranded RNA)¡C¯f¬r·L²É¥i¯à³£¬OP¼ö©Êªº¡A ¦]³Q°£¥h®Ö¿}®Ö»Ä¦ý¥]¬A¯f¬rªo¯×¡A
¦å²y¾®¶°¯À¡A ©M¯«¸gÓi»Ä?»Ã¯Àªº·L¬r²É (virosomes) ¤]³\¾ÉPµo¿N¡CµM¦Ó¡AÓ§O¯f¬r²Õ¥ó¬O«D
P¼ö©Êªº¡A ¤j·§¯à¸ÑÄÀ¬°¤°»ò§¹¾ã¯f¬r¬Ì]¯à²£¥Í¹³¬y¦æ©Ê·P«_ªº¯gª¬¦ý¦¸³æ¤¸(subunit)¬Ì]«h¤£¯à(Brydon
2005) ¡C
©I§l¯gª¬
¤ä®ðºÞ¨t²Î¹L«×¤ÏÀ³(Hyperreactivity)(Utell
1980¡A Little 1978)¡Aªýê¥Dn¤p®ð¹D(Hall 1976)¤Î´î®zªºÂX´²®e¶q(Horner
1973)¬O¦b¬y¦æ©Ê·P«_¶Ç¬V´¶³qªº¡C¹L«×¤ÏÀ³©M¤ä®ðºÞªýê¤]³\ºû«ù¤@¬qªø®É¶¡¡A ¯S§O¬O¦b¹L±Ó¯e¯f(Kondo
& Abe 1991)¡A ©M¤]³\¬O«eª¢©Ê²ÓM¿E¯À·§ªp(pro-inflammatory
cytokine profile)¥H¤z¯A¾ÉP@¨ü¯B½è©ÊP±Óì(aerosolized allergens)ªº¯à¤O
(Tsitoura 2000) ¡C
¦b¤HÃþ¬y¦æ©Ê·P«_¶Ç¬V¡A ÄY«ªÍªwª¢¯g¬°¥Dn¯f¬rªÍª¢¡A ¬O¨u¨£ªº¡C¥¦³q±`´£¥X¤U©M¤W³¡©I§l¹Dªº©µªøªºµoª¢»PÅÖ¤ò²ÓM·l¥¢¡B¥Îhyperemic
©Î¥X¦å©Ê°Ï°ì¦b³z©ú½¤(hyaline membranes) ¡B ¶Ý¤¤©Ê©M³æ®Ö²ÓMªºº¯¤J(Yeldandi
& Colby 1994) ¡C »P¥Dn¯f¬rªÍª¢¹ï¤ñ¡A ²Óµß«½Æ¶Ç¬V(bacterial
superinfection) ¬O¦b¤HÃþ¬y¦æ©Ê·P«_¤¤±`¨£ªº©M¥¦¯à¤ÞPÄY«µo¯f²v©M¦º¤`²v
¯S§O¬O¦b¦~ªøªº¦¨¤H¡C³Q¿ë»{ªº´XÓ¦]¯À¡A ¯à¸ÑÄÀ©I§l¹D²Óµß¶Ç¬V·ÀIªº¼W¥[¡A ³o¥]¬A¬Wª¬¤W¥Ö²ÓM·l¶Ë»P¤W¥Ö²ÓM»Ùꪺ¯}Ãa(Mori
1995)¡A ´î¤ÖÂH½¤ÅÖ¤òªº²M°£(Levandovsi 1985)¡A §ï¶i²ÓµßªºÂHªþ(McCullers
2002)¡A ©M¤¤©Ê¥Õ¦å²y(neutrophils)ªº¥\¯à§ïÅÜ(Abramson 1986¡A
Cassidy 1988)¡C
²ÓM¯fºA
¤HÃþ¬y¦æ©Ê·P«_¾ÉP½ÆÂø²ÓM¯fºA¡A ¥Dn¦b©I§l¹D¬Wª¬¤W¥Ö²ÓM¡A
¾ÉP«æ©ÊªÍ©M®ð¹D¯e¯f¡C¬y¦æ©Ê·P«_¯f¬r¦b©I§l¹Dªº¶Ç¬V©Mªº¯f¬r½Æ»s¾ÉP²ÓM·l¶Ë³Q»¤¾É±H¥D²ÓM³J¥Õ½èºî¦Xªº¤U°½Õ¸`(downregulation)
(Katze 1986¡A Sanz-Esquerro 1995) ¨Ã²ÓMpµe©Ê¦º¤`(apoptosis)
(Wiley 2001a)¡C«áªÌ¡A ¤S¦W²ÓMµ{¦¡©Ê¦º¤`¡A ¬O¤@¨t¦Cªº³Q©w¸qªº²ÓM¨Æ¥ó³Ì²×¾ÉP°ª®Ä²v¦aºM°£²ÓM©M¥¦ªº¤ºª«¡C²ÓMpµe©Ê¦º¤`¥i¯à¥Ñ¤£¦Pªº¾÷¨îIJµo©M¥H§ÎºA¤Wªº§ïÅܹîı¡A
¥]¬A²ÓM°©¬[(cytoskeleton)ªº¯}Ãa¡A ²ÓM½è©M®Ö¬V½è(chromatin)ªº¾®»E¡B½u²ÉÅé§@¥Î¥¢®Ä¡BDNAÂ_¸H¡A
©M³Ì«á¡A ¤p²ÓM½¤±µ³s²É¤l¦W¬° ä¤`¤pÅé(apoptotic bodies) ªº§Î¦¨¡A
«á³Q§]¾½²ÓMÄ´¦p¥¨¾½²ÓM©M¾ðª¬²ÓM(dendritic cells)²M°£¡C
¬y¦æ©Ê·P«_¯f¬r¤Þµoªº²ÓMpµe©Ê¦º¤`¬O¥ÑFas¶Ç¹F¾÷¨î©MFas¿W¥ß«H¸¹¶Ç¹Fªº¡A
Ä´¦pFADD/caspase-8 ½Æ¦XÅé¥Ñ³J¥Õ¿E×Q R (Protein Kinase
R) (PKR)©Ò§Î¦¨ ¡A ¶}©l¤@±ø²¸¯Ö®ò»Ä³J¥Õ×Q(caspase) ¦ê¬y(cascade)¡C
¥ÑIFN»¤¾É¤Î³QdsDNA¿E¤ÆªºPKR¬O¦b³\¦hä¤`³~®|(apoptotic
pathways) ¤¤ªº¤@ÓÃöÁä±±¨î²Õ¥ó (Brydon 2005)¡C§@¬°©¹²ÓMpµe©Ê¦º¤`ªº²Ä¤T±ø¸ô¡A
¬y¦æ©Ê·P«_³q¹L¯f¬r¯«¸gÓi»ÄžJ»Ã¯À(neuraminidase)¿E¤ÆÅÜ«¬¥Íªø¦]¤l¨©¥L(TGF)-Β¡CNA¥i¯à¥Ñ«P¶iTGF-Β¤Á³Î¦Ü¥¦ªº¬¡ÅD§Î¦¡¿E¬¡¼ç¦b¦b²ÓMªí±ªºTGF-Β¡CTGF-Β
°_©l¤@Ó«H®§¦ê¬y(cascade).¤pÂr¥¬¾ÉP c-Jun N ºÝ³J¥Õ½è¿EžJ(c-Jun
N-terminal kinase) (JNK) ©ÎÀ£¢¬¡¤Æ«¬³J¥Õ½è¿EžJ(stress
activated protein kinase)¡A ³y¦¨Âà¿ý¦]¯Àªº¬¡¤Æ©M«eä¤`°ò¦]ªí¹F(pro-apoptotic
gene expression) ªº¤W´å°jõX(upregulation)¡C³o±ø³~®|¡A »P¤p³J¥Õªº½u²ÉÅ齤¤ÏÀ³¡A
³Qͦ¨¦bPB1 ³J¥Õ½èªº¤@Ó¿ï¾Ü+1¾\Ū®Ø¬[ (+1 reading frame) (Chen
2001)¡A ¤w³Qħt¦b²O¤Ú²ÓMpµe©Ê¦º¤`¤Î¯à¸ÑÄÀ¦b«æ©Ê¶Ç¬V´Á¶¡ªº²O¤Ú²y´î¤Ö¯g(lymphopenia)¡C
ªÍ²Õ´¨ü¶Ë«á¦Ó¨Óªº¬y¦æ©Ê·P«_¯f¬rªº¶Ç¬V¤w»P²ÓM®ñ¤ÆÀ£¤O(oxidative
stress)¡A ¬¡©Ê®ñ(reactive oxygen species) (ROS)ªº¥Í²£
©Mµv»Ä®ñ¤Æª«¦X¦¨»Ã¯À2 (nitric oxide synthetase-2) ¦³Ãö¡A
¾ÉP©ö¤ÏÀ³¦³¬r©Ê´á®ð¤¤¶¡Åé(intermediates)ªº§Î¦¨¡CµM¦Ó¡A §Ü®ñ¾¯¡A ¦b¸ÕºÞ¤ºªº¤ä®ðºÞ(bronchiolar)²ÓM½u¤¤ªº²ÓMpµe©Ê¦º¤`¥u¬O¦³«Ü¤Öªº§@¥Î¡C
H5N1ªº¶Ç¬V¯gª¬
³¾Ãþ¬y¦æ©Ê·P«_¬O³¾ªº¶Ç¬V¯f¥ÑA«¬«~ºØ¬y¦æ©Ê·P«_¯f¬r©Ò³y¦¨¡C¨´¤µ¡A
©Ò¦³°ª«×P¯f©ÊÃzµoªº§Î¦¡¬O¥Ñ¬y¦æ©Ê·P«_¨È«¬H5©MH7 A¯f¬r©Ò³y¦¨¡C·í«e³¾Ãþ¬y¦æ©Ê·P«_¦b¤HÃþ(H5N1)
¬O§_©M¥H¤W´£¨ìªº²ÓM¯fºA¤@¼Ë¬O¥¼ª¾¼Æ¡C¥u¦³«Ü¤Ö©vÄY«©ÎP©Rªº®×¥ó³Q¬ã¨s¡C¦ý¬O¡A µL¯gª¬©Î·Å©M¯gª¬©Êªº(symptomatic)¯e¯f¬O¥i¯àªº(Buxton
Bridges 2000¡A Katz 1999) ¨Ã¨äµo¥Í²v¤]³\³Q§C¦ô¡C
H5N1 ¬y¦æ©Ê·P«_¦b¤HÃþ³Ì¦@¦Pªºªì´Á¯gª¬¬O°ª¿N¡B©M¦b¨º¨Ç¦íÂå°|ªº±wªÌ¦³ªÍª¢¡B«|ª¢(pharyngitis)¡B¤p¸z¯gª¬¡Bµ²½¤ª¢(conjunctivitis)¡A
©M«æ©Ê¸£ª¢(encephalitis)(Yuen 1998¡A Tran 2004¡A Yuen
& Wong 2005).¡Cªì´Áªº¼x¥ü¬OªÍª¢ªº¦¨¦~¯f¤H¸g±`¶i¤@¨B¤Fµo®i¦¨¹³ARDSªº¯e¯f¡C¦bH5N1
¬y¦æ©Ê·P«_ªºP©R¯f¨Ò¡A ©ö¤ÏÀ³ªº¾½¦å¯gÔ¸s(Hemophagocytic Syndrome)³Q´yz¬°¤@Ó¬ð¥Xªº¯SÂI¡C
¦bªÍ¯f¥H²Õ´ÂX´²ªÍM·l¶Ë©M²ÓM¶¡ªºÅÖºûÅܩʤ§¥~¡A ªÍ¥~³¡ ¦ì(extrapulmonary)ªº¤¶¤J¤w³Q´yz¬°¼sªx©Ê¨x¤¤¥¡¤p¸¤ùÃa¦º(extensive
hepatic central lobular necrosis)¡A «æ©ÊµÇ¤pºÞÃa¦º (renal
tubular necrosis)¨Ã²O¤Ú¯Ê¥F(lymphoid depletion) (To
2001)¡A ÁöµM¦b¤ÀÂ÷«á¨S¦³¯f¬r³Qµo²{¡A¤ÏÂà¿ý»E¦XÃì¤ÏÀ³(Reverse Transcription-Polymerase
Chain Reaction©M§K¬Ì¬V¦â¡]immunostaining¡^´ú¸Õµo²{¥i·»¸Ñªº¤¶¥Õ½è¤l-2
·P¨ü¾¹(interleukin-2 receptor)¡B¥Õ½è¤l-6 ( interleukin-6)©M¤zÂZ¯À¦÷º¿(interferon-gamma)¦³¼W¥[¤F¡C¥t¥~¡A
¸~½FÃa¦º¦]¯Àªüº¸ªk(tumor necrosis factor-alpha) mRNA
¦b¨ä¥¦¥H¤HÃþH5N1 ¬y¦æ©Ê·P«_ªºªÍ²Õ´ªº¯f¨Ò¤¤³Qµo²{(Uiprasertkul 2005)
¡C
»P¤HÃþH1N1 ¯f¬r¤ñ¸û(Hayden 1998)¡A ±q1997
¦~ªº»´äH5N1«~ºØ¤w³Q´£Ä³¨ä¦³®Ä¤O¦a¥ÑNS°ò¦]²£ª«»¤¾É«eª¢©Ê²ÓM¿E¯À¥]¬AIL-10¡BIFNΒ¡BRANTES¡BIL-6
©M¯S§O¬OTNF (Cheung 2002¡A Lipatov 2005¡A Chan 2005)¡C³o¨Ç¬ã¨sªº§@ªÌ°²³]¡A
¦bP©R©Ê¤HÃþ¶Ç¬V©Ê³¾Ãþ¨È«¬H5N1¤¤¡A ³Ìªìªº¦b©I§l¹Dªº¯f¬r½Æ»sIJµo¥Ñ¤@Ó©ö¤ÏÀ³ªº¾½¦å¯gÔ¸s©Ò½ÆÂø¤Æªº²ÓM¯À·¼É(hypercytokinemia)
¤]³\¬O¦³§O©ó³q±`¤Hªº¤l«¬¥H¥~ªº¬y¦æ©Ê·P«_A H5N1¶Ç¬Vªºµo¯fì²z (To 2001)¡C¦bH5N1
³¾Ãþ¬y¦æ©Ê·P«_ªºP©R¯f¨Ò¤¤¨Ã¥¼µo²{²Óµß«½Æ¶Ç¬V(To 2001)¡C³oÆ[¹î¤]³\¬O³o¨Ç³ÌÄY«ªº¦´ÁP©R¯f¨Òµ²ªGªº°¾¨£¡A
°²³]¦a¨S¦³®e³\«½Æ¶Ç¬Vªºµo®i¡C
¬y¦æ©Ê·P«_«ç¼Ë³Q¶Ç¼½¨ì¨ä¥L¤H¤¤?
©I§l©Ê¶Ç¼½¨ú¨M©ó±a¯f¬r®ð¸ü·L²É©M¯B½èªº¥Í²£¡C¦bÁ¿¸Ü©M¥¿±`©I§l´Á¶¡¡A
¯B½è·|¥Í²£¡C±q»óµÄ¬y¥Xn¨D¥´¼QÀ¡©M¦pªG¶Ç¬V»s³y¤F¤@ºØ»ó¤Àªcª«¡A ¨º«K¥i§ó¦³®Ä¦a¬y¥X¡C¼QÀ¡¥Í²£20¡A000
¤pºw»P¥u¦³«y¹Â¤ñ¸û´X¦Ê¤pºw¼Q¥X¡C³Ì¤jªº¤pºw¤U¶^¨ì´X¦Ì¤§¤ºªº¦a±¡C³Ñ¾l¤pºw²¾°Êªº¶ZÂ÷¨ú¨M¦b¥¦Ìªº¤j¤p¡Cª½®|1-4£gmªº¤pºw¤]³\ªø´Á«O«ù°±¯d¤Î¨ì¹F¤U©I§l¹D¡C¹êÅç©Ê¬y¦æ©Ê·P«_¶Ç¬Vªº§ÓÄ@ªÌÅã¥Ü¡A
¤p¤pºw¦b¤ä®ðºÞªº§l¤J¤ñ¸û¤j¤pºwªº¤J¤W©I§l¹D©Î²´²yµ²½¤ªº±µºØ¬°¦h¡C (Alford 1966¡A
Little 1979¡A Bridges 2003). ¦pªG¯f¬r¦b¦´Á¶Ç¬V¤¤©ó¤U©I§l¹D½Æ»s¡A
³o·|¾ÉP§ó¤p¥B¸ü¦³§ó¦h¯f¬r¤Î§ó°ª¶Ç¬V¤Oªº¤pºw¥X²{¡A ¦]¬°¯S²§©Ê§K¬ÌºÊ±±¨t²Î¤´µM¥¼«Ø¥ß¡CH5N1±q°Êª«¨ì¤Hªº¶Ç¬V¤]³\¥H¤£¦Pªº¤è¦¡ª½±µ(©M¶¡±µ)±µÄ²³Q¶Ç¬Vªº¸V¯b¡C
°ª§ðÀ»²v¬O¾ÉP¬y¦æ©Ê·P«_A ¬y¦æ©ÊÃzµo©Ò¥²»Ýªº¡C©Ò¥H¡A ¥V¤Ñ¬y¦æ¯f¦b¼Ú¬w©M¥_¬ü¬w¤]³\¦]¬°§ó¥[¦hªñ¶ZÂ÷ªº±µÄ²©M³r¯d¦b¤í³q·ªº©Ð¶¡¡C¬y¦æ©Ê·P«_¯f¬rªº¾AÀ³¤O¬O±jªº:¤£ª¾¦ó¬G¥¦¥Í¦sªº¯à¤O¦b¸û§Cªº¬Û¹ïÀã«×©M§ó§CªºÀô¹Ò·Å«×¬°¨Î(Hemmes
1960) ¡C³¾Ãþ¬y¦æ©Ê·P«_(H5N1) ¤]³\¤£¤Ó¾AÀ³¤pºw¶Ç¬V: ¼ç¥ñ´Á¬O¸ûªøªº(Chotpitayasunondh
2005)¡A ²z½×¤W¦b¬y¦æ©Ê´Á¶¡¸û³y¦¨¸û¤Öªº³\¦h¤Hªº¤@¨Ö¶}©l¬V¯f¡C¤p¸z½Æ»s©M¯gª¬¦b©I§lÅã¥Ü¦Ü¤@Ó¬P´Á(Apisarnthanarak
2004 ¥H«e)¡A ¤¹³\¯S²§©Ê§K¬Ì¤ÏÀ³¦b¶Ç¬V©Ê¤pºw¶Ç¼½¤§«e°_©lºtÅÜ¡Cµ²ªG¡A¦b³¾Ãþ¬y¦æ©Ê·P«_ªº»ó«|½Æ»s¸û¤Ö¦b¤HÃþ¬y¦æ©Ê·P«_µo¥Í(Peiris
2004) ¦ý¯f¬r½Æ»s¬O³Q©µªø(Beigel 2005) ¡Cª½¨ì²{¦b¡A H5N1¦b¤H¤§¶¡¶Ç¬V¬O¨u¨£ªº(Buxton
Bridges 2000¡A Ungchusak 2005)©M¬Û·íµL®Äªº¡CÁ`¦Ó¨¥¤§¡A ³¾Ãþ¬y¦æ©Ê·P«_¯f¬r(H5N1)
¾Ú±À´ú¤H¶Ç¤Hªº¶Ç¬V©M³Ì«á¹F¨ì¬O§_¨¬°÷¦³®Ä¤Þ°_¬y¦æ©Ê©Î¤j¬y¦æªº·P¬V²vn´XÓ¶Ç¥N(passages)¡C
§K¬Ì¾Ç
¬y¦æ©Ê·P«_¾ÉP±J¥D«æ©Ê·P¶Ç¬V©M°_©l§K¬Ì¤ÏÀ³¦ê¬y(cascade)
¿E¬¡´X¥G§K¬Ì¨¾¿m¨t²Îªº©Ò¦³³¡¥÷¡C¤j¦h¼Æ³Ìªìªº¥ý¤Ñ©Ê¤ÏÀ³¡A ¥]¬A²ÓM¿E¯ÀÄÀ©ñ(IFNΑ/Β)¡A
·J¶°¶Ý¤¤©Ê²É²ÓM(neutrophil Granulocytes) ©Î¦ÛµM±þ¤â²ÓM(natural
killer cells) (Mandelboim 2001¡A Achdount 2003)¡A
©M²ÓM¬¡¤Æ§@¥Î¡A t³d°_©l«æ©ÊÁ{§É¯gª¬(°Ñ¨£¤W±) ¡C¥ý¤Ñ©Ê§K¬Ì¬O«á¤Ñ©Ê§K¬Ì¤ÏÀ³(adaptive
immune response)¥²nªº¡A º¥ý¡A ¨î³Ìªìªº¯f¬r½Æ»s©M§Üì¸Ë¸ü¡A ¤Î²Ä¤G¡A
¦]¬°«á¤Ñ©Ê§K¬Ì¤ÏÀ³ªº§Üì±M¤@©Ê²O¤Ú²ÓM¬O³Q¦b¥¦Ì»P¯f¬rªº¤¬§@¥Î´Á¶¡¡A ³Q¥ý¤Ñ©Ê§K¬Ì¨t²Î²ÓM»¤¾Éªº¨ó¦P¨ë¿E¤À¤l(co-stimulatory
molecules)©Ò¿E¬¡ (¹Ï3)¡C¬y¦æ©Ê·P«_¯f¬r¡A µM¦Ó¡A ͽX¦b«Dµ²ºc©Ê³J¥Õ½è1(NS1)
¾÷¨î¤¤¸úÁשM¹ï§ÜIFNΑ/Β ¤ÏÀ³¡CNS1¥i¯à¥i¥H¹jÂ÷¯f¬rdsRNA¨¾¤î¥Ñ²ÓM·PÀ³¾¹ÃѧO³o¦MÀI¤À¤l§_«h·|IJµoIFN
Α/Β ÄÀ©ñ(Garcia-Sastre 1998¡A Garcia-Sastre
2005).Àò±o©Ê§K¬Ì¤ÏÀ³(adaptive immune response)»Ýn¼Æ¤é¤~¦³®Ä¦ý¤§«áÀ°§U¥]§t¯f¬r¶Ç¼½¡A
n®ø·À¯f¬r¡A ©M³Ì«á«Ø¥ß°O¾Ð¤ÏÀ³¥H½T«O¥iªø´Á©Ê©è§Ü¦P·½¯f¬rªº¦A·P¬V¡C¦b¬y¦æ©Ê·P«_¨È«¬ªº¥æ®t«OÅ@«Ü¤Ö³Q¹îı¨ì¨Ã¥B¶Ç¬V®Ú¥»µLªk»¤P¾î¸ó¨È«¬©ÎA¤ÎB«¬¤§¶¡ªº«OÅ@(Treanor
2005). ¬y¦æ©Ê·P«_·P¬V¾ÉP¨t²Î¤Î¦a¤è©Ê§ÜÅé (Åé²G§K¬Ì) (humoral immunity)¡A
¨Ã¬r±þ©ÊT²ÓM(cytotoxic T cell)¤ÏÀ³ (²ÓM©Ê§K¬Ì) (cellular
immunity)¡A ¨CÓ³£¹ï±q«æ©Ê¶Ç¬Vªº´_¤¸©M¦A·P¬Vªº©è§Ü¤§¬°«n¡C

¹Ï3 . ¹ï¬y¦æ©Ê·P«_¯f¬r¶Ç¬VªºÅé²G©M²ÓM©Ê§K¬Ì¤ÏÀ³¡CÅé²G©Ê§K¬Ì¨t²Îªº¤À¤ä¥]¬AB
²O¤Ú²ÓM(¥ª)¡A ¦b»P¬y¦æ©Ê·P«_¤¬§@¥Î¥H«á¡A ¤À¤Æ¦¨¤Àªc§ÜÅ骺¦å¼ß²ÓM¡C²ÓM©Ê¤ÏÀ³(¥k)
¥H§Üì§e²{³q¹LMHC I (¶Â¦â) ¨Ã¥BII (ÂŦâ) ¤À¤l¥Ñ¾ðª¬²ÓM¶}©l¡A µM«á¤ÞP¬¡¤Æ§@¥Î¡B§Üì¨ãÅéT
²ÓMªº¿E¼W©M¤À¤Æ(CD4 ©ÎCD8) ¡C³o¨Ç²ÓMÀò¨ú°Ê§@¾¹²ÓM§@¥Îª½±µ¦aÀ°§U¡A ÄÀ©ñ²ÓM¿E¯À¡A
©Î¶Ç¹F²ÓM¬r©Ê(cytotoxicity)«áÃѧO§Üì (Adapted from Flint
2004)¡C¨S¦³¦b¦¹³QÅã¥Üªº¬O¥Ñ¬y¦æ©Ê·P«_»¤¾Éªº²ÓM°O¾Ð§K¬Ì¤ÏÀ³©M¤£¦P§Î¦¡ªº¥ý¤Ñ©Ê§K¬Ì¤O¡C
Åé²G©Ê§K¬Ì
§ÜÅé(¦pIgG¡A IgA)¬O¥ÑB ²ÓMµo®i³Ì«á¶¥¬qªº¦å¼ß²ÓM¥Í²£¡A
»ÝnB ²ÓM¤wÃѧO§Üì¤Î¤w³QCD4 T ²ÓM©MT ²ÓMl¥Íªº²ÓM¿E¯À(¹Ï3)¨ë¿E¡C»PT
²ÓM¤£¦P¡A B²ÓM¥i¥H¨ä즳§Î¦¡ÃѧO§Üì¡C§Üì¯S²§©Ê±q°ò¦]ªºÀH·N«¾ã½s½X¦b²ÓM¤ºªº§K¬Ì²y³J¥Õ°ª¥iÅܲ§(hypervariable)°Ï°ì¥X²{¡A
¾¨ºÞ²ÓM¤´µM¦b°©Åè¡CµM«á¡A ¥¼¬¡¤Æ(Native) B ²ÓM¶i¤J´`Àô¡A ³q¹L¦å²G©M²O¤Ú¸¢(lymphatics)¦Ü²Õ´©M²O¤Ú¸¢¾¹©x¡C¦b²O¤Úµ²(lymph
nodes)¡A ¥¼¬¡¤Æ(native) B ²ÓM¥Ñ¥¦Ìªºªí±§ÜÅéÃѧO¦P·½§Üì¡A Åܦ¨¬°¿E¬¡¡A±qIgM
Âà´«(switch) ¦ÜIgG ¥Í²£(Ãþ«¬Âà´«) (class-switch)¡A ¼W¥[¥¦Ìªº§K¬Ì²y³J¥Õ¯S²§©Ê©M¿Ë¦X¤O(affinity)¡A
¤Î·í²ÓMÄ~Äò¦b²ÓM¿E¯Àªº¼vÅT¤U¤Àµõ¡A ¤À¤Æ¦¨¦å¼ß²ÓM©Î°O¾ÐB ²ÓM¡C·íIgA ³Q¹B¿é¾î¸ó¤W®ð¹DªºÂH½¤¤W¥Ö²ÓM¡A
¨ä¥Î¥H¤¤©M¤Î²M°£¯f¬r¶Ç¬V¡A IgG ¥Dnt³d«OÅ@¤U©I§l¹D¡C (Palladino 1995¡A
Renegar 2004)¡C
¬y¦æ©Ê·P«_¶Ç¬V¾ÉP¹ï¬y¦æ©Ê·P«_¿}³J¥ÕHA¡A NA¡A M ©MNP
³J¥Õ½èªº§ÜÅé¨t²Î©Ê¥Í²£¡C¨Ò¦p¡A HA ±M¤@©Ê§K¬Ì²y³J¥Õ¡A ¥]¬AIgM ¡BIgA ©MIgG¡A
¥X²{¦b¯f¬r±µºØ¤§¨â¬P´Á¤º¡C§ÜNAµo®i»P¦å²y¾®¶°¯À§Ü¤Æ©Ê§ÜÅé(hemagglutinin-inhibiting
antibodies)ªºµo®i¥¦æ¡C¦b¶Ç¬V¥H«áªº4-7 Ó¬P´Á¤§¶¡¡A ¦b§ÜÅéºw©w¶q«K¹F¨ì®p³»¡A
ÀHµÛ¥Ãªº¤U°¡C¦b¶Ç¬V¥H«á¡A §ÜÅé¥i«O¯d´X¦~¡A ¾¨ºÞ¨S¦³«´_¼ÉÅS(re-exposure)¡C§ÜHA§ÜÅé»P«OÅ@§K¨ü¦P·½¯f¬rªº¶Ç¬V¤Î¤Þµo¯e¯f¡A
¨Ã¥B»¤¾É¤¤©M§ÜÅ骺¬O¬Ì]§K§Ð±µºØ·í¤¤ªº¤@Ó¥Dn¥Ø¼Ð¡C¦å²MHA §Ü¤Æºw©w¶q1:40 ©Î§ó¤j¡A
©Î¦å²M¤¤©Mºw©w¶q1:8 ©Î§ó¤j¡A À³¥i«OÅ@§K¨ü¶Ç¬V¡C¦b¸û¦Ñªº¤HÅ餤«h»Ýn§ó°ª¤ô¥ªº§ÜÅé¡A
¤~¥i§¹¥þ«OÅ@ (Treanor 2005) ¡C
»P§ÜHA§ÜÅé¹ï¤ñ¡A §ÜNA§ÜÅ餣¯à¤¤©M¯f¬r·P¬V¡A ¦ý¬O¤Ï¦Ó´î¤Ö¯f¬r±q³Q¶Ç¬Vªº²ÓM°ª®Ä²vªºÄÀ©ñ
(Johansson 1989) ¡C³o¬O¦]¬°¯«¸gÓi»ÄžJ»Ã¯À¼A¶}ªþ¦³³Ìªñ§Î¦¨ªº·L²Éªº²ÓM·P¨ü¾¹¤¤Öº¾T¼h»Äªº´Ý°ò¡C§ÜNA
§ÜÅé¥i¥H«OÅ@§K¨ü¯e¯f¤Îµ²ªG´î¤Ö¯f¬r´²¼½ªº¯à¤O©MÄY«ªº¯gª¬¡C¦³¤H´£Ä³¤]¦³¬Û¦üªº§@¥Î¹ï¬y¦æ©Ê·P«_A
ªºM2 ³J¥Õ½èªº§ÜÅé¡A ÁöµMÁ`¬A¨Ó»¡¡A §ÜÅé¹ï¤º³¡§Üì¬O«D¤¤©M©Êªº¡A ¥¦·|§ó§Öªº®ø¥¢©M¬Ý¨Ó¤£¯à¥R·í¨¾Å@§K¬Ìªº¤@Ó¨¤¦â¡C
ÂH½¤§K¬Ì¤ÏÀ³¹ï¬y¦æ©Ê·P«_¡A ¨Ì·Ó¦b»ó¤º¥i´ú¶q±oªº¤Àªcª«¡A ¥H¹ïHA
ªºIgA ©MIgG1¬°¯S¼x¡CÂH½¤§ÜHA IgG ¤ô¥»P¨ä¦å²M¤ô¥¦³±K¤ÁÃöÁp¡A ªí©ú±q¨t²Î¹j¶¡ªº³Q°ÊÂX´²¡A
¦ýIgA ¬O§½³¡¦a³Q¥Í²£¡C¬ã¨s«ØÄ³¡A¹ï¦A·P¬Vªº©è§Ü¬O¥Dn¦a¥Ñ§½³¡©Ê³Q¥Í²£ªºHA ±M¤@©ÊIgA©Ò¶Ç¹F¡AÁöµM¤]³\¬O©MIgG¬ÛÃöªº(Renegar
2004)¡C¦pªG¦³¥R°÷ªº¿@«×¡A ÂH½¤©Î³æ¿W¨t²Î©Ê§ÜÅé¥i¥H¬O¨¾Å@©Êªº¡A ¦ý³Ì²z·Q«OÅ@µo¥Í©ó¦å²M©M»ó§ÜÅé¨Ã¦s®É
(Treanor 2005)¡C§ÜÅé¦b§K¬Ì¤¤¹ï¬y¦æ©Ê·P«_ªº¦æ°Ê¬O¥Ñ¤¤©M¯f¬r¡A ©Î¥Ë¸Ñ³Q¶Ç¬Vªº²ÓM¯f¬r³q¹L¸ÉÅé©Î§ÜÅé¨Ì¿à«¬²ÓM¬r©Ê§@¥Î
(antibody-dependent cellular toxicity)¡C
¦b«æ©Ê¯f¬r¶Ç¬V¯f¬r¤¤®ø·À¯f¬rªº¥D¤H¬O¹ï¨Ó¦Û¦P¼Ë¯f¬rªº¶Ç¬V¦³´¶¹Mªº§K¬Ì¤O¡CµM¦Ó¡A
¾¨ºÞ¦³¬¡ÅDªº§K¬Ì²M°£¡A ¥Ñ¬y¦æ©Ê·P«_¯f¬r³y¦¨ªº«æ©Ê¶Ç¬V¤@¦Aµo¥Í¡C³o¬O¦]¬°¬y¦æ©Ê·P«_Åã¥Ü¤@¥i¶ì©Êªºµ²ºc¤Î¨ä¯à®e§Ô¦b¥¦ªºµ²ºc³J¥Õ½è¸Ì¦³³\¦h®ò°ò»Ä´À¥N¦Ó¨S¦³¥¢¥h¥¦ªº¶Ç¬V¤O¡C¨Ò¦p¡A³s±µ¤À¤lHAªºÖº¾T¼h»Ä·P¨ü¾¹¡A
t³d¯f¬r¹ï¥Ø¼Ð²ÓMªº¶i¤J¡A ¨Ã¥B¬O¤@Ó¬°¤¤©M§ÜÅé©M²ÓM¬r¯ÀªºT ²O¤Ú²ÓM¥Dn¥Ø¼Ð¡A ®i¥Ü³sÄò§K¬ÌÀ£¤O¡C³o§K¬Ì¿ï¾Ü©Î¦h¼Ë¤Æ¡A±q½Æ»sªº¿ù»~¥X²{¡A
¾ÉP»´·LHAÀH®É¶¡ªºÅܲ§¦Ó¤¹³\¯f¬r°kÁפHÃþ§K¬Ì¤ÏÀ³ (§Üìº}²¾)¡]Antigenic drift¡^¡C³o¨ÇÅܰʬO¬y¦æ©Ê·P«_¨C¦~¦³¬y¦æ©Ê¶Ç¼½ªºì¦]©M¦b¨C¦~¬y¦æ©Ê¤§«e»Ýn¤½¦¡¤Æ·s¬Ì]¡C¬Û¤Ï¡A
¦b°ò¦]²Õ©Î°ò¦]²Õ¬qªº¦Aµ²¦X©Î«²Õ¥H«á¡A ¦]¬°°ò¦]§¹¥þ¦aͽX¦¨·sªí±³J¥Õ½è¡A §Üìº}²¾¬O¦b¯f¬rªí±³J¥Õ½è¤Wªº¤@Ó¥DnÅܤơC¨C·í¬V¦âÅ齯»s®É¡A
§ÜìÂà´«¬O¥i¯àªº¡C¬Û¤Ï¡A §Üìº}²¾¥u¯à¦b¬Y¨Ç±¡ªp¤§¤Uµo¥Í¡A ¬O¬Û¹ï¦a¨u¨£©M¥i¯à¬O¤j¬y¦æªº¤@Óì¦]¡C
²ÓM§K¬Ì¤ÏÀ³
¾ðª¬²ÓM³QÅã¥Ü¦b¶}©l©M¾r¾pT ²O¤Ú²ÓM¤ÏÀ³¤¤§êºt¤@Ó¥Dn¥D¨¤¡C¥¦Ì¬Oµ}²¨¦a¤À§Gªº°©Åèl¥Íªº¥Õ¦å²y¾E²¾¤p²Õ±Mªù¬°§Üì¹ïT
²ÓMªºÄá¨ú¡A ¹B¿é¡A ³B²z©M®i¥Ü (¹Ï3) ¡C°ò¥»ªº½d¨Ò¬O¡A ¦s¦b©óªÍ¤ºªº¾ðª¬²ÓM±q«I¤Jªº¯fì¥Íª«¨ú±o§Üì¡A
Åܬ°¿E¬¡¡A ¨ÃÀH«á©¹§½³¡©Ê¤Þ¬y²O¤Úµ²(Legge & Braciale 2003) ¡C§Üì¼Ë¥»¤w³B²z©M³Q©T©w¦b¾ðª¬²ÓMªí±§@¬°¥Ñ¥Dn²Õ´¬Û®e©Ê½ÆÂøÅé(major
histocompatibility complex )(MHC)¤À¤lªºÁY®ò»Ä(Silver
1992). ¦b²O¤Úµ²¡A ²{¦b¦¨¼ô¾ðª¬²ÓM°ª®Ä²v¦a¥Ñ¥ô¦ó¤@ÓT ²ÓM»P¦b¾ðª¬²ÓMªí±ªº¯S²§©Ê¥~¨Ó-ÁY®ò»Ä-MHC
½Æ¦XÅé·P¨ü¾¹Ä²µo¤@Ó§K¬Ì¤ÏÀ³(Shortman & Liu 2002)¡C±q¾ðª¬²ÓMªº¯f¬r¶Ç¬Vªº¤º¦]©Ê§Üì³Q³B²z¤Î³Q®i¥Ü³q¹LMHC
I ¤À¤l¦ÜCD8 T ²ÓM¡C¥~¦]©Ê§Üì³q¹LMHC II ¤À¤l¹ïCD4 T ²O¤Ú²ÓM³Q®i¥Ü¡C¤GªÌ¾Ü¤@¦a¡A
¾ðª¬²ÓM¤]³\¥i®i¥Ü¥¦Ì±q³Q¶Ç¬Vªº²ÓMÀò¨úªº§Üì¡A ©ÎÂಾ§Üì¦Ü¦b²O¤Úµ²¤º¾Fªñªº¾ðª¬²ÓM¡A
µM«á¥Ñ¤@Óµ{§Ç¥s¥æ¤e§Üì´£§e(cross-presentation)°_©lCD8 T²ÓM¤ÏÀ³
(Belz 2004¡A Heath 2004¡A Wilson 2006).³Ìªñ³Q¿E¬¡ªºT
²ÓMÀò¨ú¨ü°Ê¾¹²ÓM§@¥Î©M²¾©~¦Ü¦bªÍ¤ºªº¶Ç¬V¦aÂI¥H«K¶Ç¹F¥¦Ìªº§Ü¯f¬r¬¡°Ê(¹Ï3) ¡C
¦b·P¬V´_¤¸¥H«á¡A §K¬Ì¾Ç°O¾Ðª¬ºA±µµÛ¦Ó¨Ó¦bÓÅé §ó¯à±±¨îÀH«á¦P¼Ë¯f쪺¶Ç¬V
(Ahmed & Gray 1996)¡C°O¾Ð¬O¥Ñ§Üì¯S²§©ÊT ²ÓM¥H«ùÄò¼W¥[ªºÀW²v©Òºû«ù
¡A »P¥¼¬¡¤Æ (na?ve) T ²ÓM¤ñ¸û¡A ´î¤Ö¤F¦@¨ë¿E(co-stimulatory)«H¸¹ªº»Ýn¡A
©M¹ï§Üì¦A¨ë¿E(restimulation)ªº¦³¨³³tªº¤ÏÀ³ (Woodland & Scott
2005). ¥ç¦³ÃҾڶɦV©ó¬y¦æ©Ê·P«_¯S²§©ÊCD8 °O¾ÐT ²ÓM¦b¤HÃþªÍ¸Ìªº²Ö¿nªº¦aÂI¦³¯S²§©Ê¡A
¬°¹ïªÍ¦A·P¬V§@ºò±µªº§K¬Ì©Ê«OÅ@(de Bree 2005¡A Wiley 2001b)¡C¦b¬y¦æ©Ê·P«_¶Ç¬V´Á¶¡¡A
CD4 ©MCD8 °O¾ÐT²ÓM¨È¸s¡]subset¡^¤ÏÀ³¡A ©M¶Ç¹F±±¨î¬y¦æ©Ê·P«_¯f¬rªº¦A·P¬V¡A
¬O»Pªì¦¸·P¬V¯f¬rªº²M°£¥Dn¨Ì¾aCD8 T ²O¤Ú²ÓMªº§@¥Î¤£¦P(Woodland 2003)¡C
¥t¤@«n¯S¼x¡A ¨Ò¦p¦b¬y¦æ©Ê·P«_¶Ç¬V¡A ¬OCD4 T ²O¤Ú²ÓM»²§UB
²O¤Ú²ÓM²£¥Í§ÜHA©M§ÜNA §ÜÅé(¹Ï3) ¡C¦bHA¥ÑCD4 T »²§U²ÓMÃѧOªº¯f¬r§ÜÅé¿ëÃѪº°Ï°ì¦³§O©ó¥Ñ³Q¨º¨Ç§ÜÅéÃѧOªº°Ï°ì¡CT
»²§U(Th) ²ÓM¤]³\¥ç«P¶i¯f¬r¯S²§©ÊCD8 ²ÓM¬r©ÊT ²O¤Ú²ÓMªº²£¥Í¡CTh ²ÓM¦Ü¤Ö¥i®Ú¾ÚÃþ«¬¥¦Ì¥Í²£ªº²ÓM¿E¯À¡A
¶i¤@¨B³Q²Ó¤À¬°Th1©MTh2 ²ÓM¡A¡C¦b¦Ñ¹«¡A ¬y¦æ©Ê·P«_¶Ç¬V¾ÉP¤@Ó±j¯PªºTh1 ¤ÏÀ³¡A
¦ýTh2²ÓM¿E¯À¡A (IL-4 ¡BIL-5 ¡BIL-6¡A IL-10) ¥ç³Qµo²{¦b³Q¶Ç¬V°Êª«ªºªÍ³¡¡C¤@¨ÇÃÒ¾Úªí©ú¡A
¨¾Å@§K¬Ì¬O¥Ñ¹³Th1¤ÏÀ³³Q¶Ç¹F¡C¦b¬y¦æ©Ê·P«_¶Ç¬V¡A CD8 ²ÓM¬r¯ÀªºT ²O¤Ú²ÓM(CTL)
±qHA ©Î¤º³¡³J¥Õ½èM ¡BNP¡A ©Î³Q®i¥Ü¦bMHC ²Õ I ¤À¤lªºPB2ÃѧO¯f¬r§ÜÅé¿ëÃѪº°Ï°ì
(Treanor 2005) ¡C®Ú¾Ú¥¦Ìªº§Üì¯S²§©Ê¡A CTLs ¤]³\¬O¨È¸s ¯S²§©Êªº©Î¡A
¦pªG¥¦ÌÃѧO¤º³¡§Üì¡A ¯à¼e¼s¥æ¤e¦a»P¬y¦æ©Ê·P«_A¤ÏÀ³¡C°Êª«¹êÅç¨Ï¥Î±Ä¯Ç¦¡CTLs½Õ°ÊÅãÅS¤F¥¦Ì¦b¶Ç¬V´Á¶¡ªº¼W¥Í©M¾E²¾¼Ë¦¡(Lawrence
& Braciale 2004¡A Lawrence 2005) ¨Ã¨ä¡A±q¬y¦æ©Ê·P«_¶Ç¬V¹F¨ì²¬Â¡ªº¼ç¤O¡CµM¦Ó¡A
¥L̦b¬y¦æ©Ê·P«_ªº±±¨î¤¤¤£¬Oµ´¹ï¦a»Ýn¡C
¦b¤HÃþT²O¤Ú²ÓM¤ÏÀ³¹F³Ì°ªÂI¤j¬ù¦b«á¶Ç¬Vªº²Ä14¤Ñ ¨Ã¥B¬y¦æ©Ê·P«_¯S²§©ÊCTLs
ªº¤ô¥»P¦¨¤H¯f¬r½Æ»sªº´Á¶¡©M¤ô¥ªº´î¤Ö¦³¤¬¬ÛÃöÁp¡C°O¾ÐCD8 T ²ÓM¤]¥i¦b§ïµ½¯e¯fÄY«©Ê©M«P¶i¦A·P¬V®Éªº´_¤¸¥R·í¤@Ó¨¤¦â¡C³Ìªñ°Êª«¬ã¨s«ØÄ³¡A
¦bªÍ¸Ìªº¥l¦^¤ÏÀ³(recall response) ¤À¬°´XÓµu¼È©M¦b¸Ñå¾Ç¤W³Q¤ÀÂ÷ªº¤À©ú¶¥¬q¡C²Ä¤@¶¥¬q¥Ñ¾n¦bªÍ®ðºÞªº°O¾ÐT
²ÓM¶Ç¹F(Woodland & Randall 2004)¡C«n¦a¡A ·í¯f¬r¶qÁÙ¬O«D±`§C®É¡A
³o¨Ç²ÓM¯à¹ï¶Ç¬Vªº²Ä¤@¼x¥ü¦³¤ÏÀ³ ¡C¥Ñ©ó¨ü®ðºÞÀô¹Ò¨îµLªk¹ï¶Ç¬V¦Ó¼W¥Í¡A ¥¦Ì¤]³\¯à²£¥Í²ÓM¿E¯À¥H¨î¯f¬r½Æ»s©M¦b¤W¥Ö¶Ç¼½ªº¡C²Ä¤G¶¥¬q¤ÏÀ³¡A
¦b³Ìªì¼Æ¤Ñªº¤ÏÀ³¬O¥Ñ¨³³t¦a³Q¼x¤J¨ì®ðºÞªº°O¾ÐT²ÓM©Ò¶Ç¹F¡C²Ä¤T¶¥¬q¬Oµo¥Í¦b¦¸²O¤Ú¸¢¾¹©x°O¾ÐT²ÓM§ÜìÅX¨ÏªºÂX®i¡C³o¨Ç°O¾Ð²ÓM¥H´X¤Ñ¦b²O¤Ú¸¢¾¹©x¼W¥Í©M¥u¯à¦b¨ü¶Ç¬Vªº¤j¬ù5
¤Ñ«á¡A ³Q¼x¤J¨ì®ðºÞùØ¡C(Woodland & Randall 2004)¡C³o¨Ç±q°Êª«¹êÅç¤Þ°_ªº½ÆÂø¼Ò«¬¬O§_¾A¥Î©ó¤HÃþªº±¡ªp¬O¤£©úªº¡C
µM¦Ó¡A ¬°¤F§ï¶i¥¼¨Ó¬Ì]ªºpµ¦¡A ¥²»Ý§ó¦n¦aÁA¸Ñ§K¬Ì¤ÏÀ³ªºÃþ«¬¤Î©ó¬y¦æ©Ê·P«_¶Ç¬V´Á¶¡¦³®Äªº°O¾Ð¡A
T²ÓM¤ÏÀ³ªº¥Í²£¤ÎºûÅ@¡C
µ²½×
§Ú̬ݨ£¤F¬y¦æ©Ê·P«_¯f¬r¶Ç¬V«ç»ò¾ÉP¼ö©Ê©I§l¯f¯gªº«æ©Êµo®i¡Cµo¯fì²z¥H¦bªÍ¤ºªº¯f¬r¨³³t½Æ»s©M´²§G¬°¯S¼x¡A
³y¦¨§½³¡©M¨t²Î©Êµoª¢¤Î²ÓM¿E¯ÀÄÀ©ñ¡C³o¨Ç¨Æ¥ó¡A »PÀò±o©Ê§K¬Ì¤ÏÀ³¡A À°§U´î¤Ö¯f¬rt¾á¡A
®ø·À¯f¬r¡A ©MIJµo¯e¯f´_¤¸¡CÅé²G¤Î²ÓM©Ê§K¬Ì¤ÏÀ³¡A ¥Ñ¶Ç¬V©Î±µºØ»¤¾É¡A ´£¨ÑÓÅé¤Î¤j²³¹ï¬ÛÃö¯f¬r«~ºØªº«ù¤[©Ê§K¬Ì¨¾Å@¡CµM¦Ó¡A
¬y¦æ©Ê·P«_¥i³q¹L§ÜìÂಾ©Mº}²¾¡A ¯}Ãa³o¶Ç¬V©Î¬Ì]l¥Íªº§K¬Ì¡A ³y¦¨¬y¦æ©Ê©M¤j¬y¦æ©ÊÃzµo¡C§Þ³N§ïµ½¡A
¥]¬A°ò¦]©M¥\¯à¬ã¨s¡A ±NÀ°§U¶i¤@¨B¤F¸Ñ¾ú¥v©Ê©M·í«e¬y³qªº¬y¦æ©Ê·P«_¼@¬r«~ºØªºµo¯fì²z¡C§Æ±æ³o¨ÇÃö©ó¤HÃþªÍ³¡¯f¬r§K¬Ì¨¾¿m¾÷¨îªºª¾ÃÑ©M°ª«×²z¸Ñ¡A
±N«P¶i¿ï¾Ü§ó¦nªºªvÀø©M¹ï¤µ«á¬y¦æ©Ê·P«_¯f¬rªºÅܲ§¡A ¦³§ó¦h¦³®Äªº¬Ì]¨Ã¥i¨³³t¦aµo®i¤Î¤À§G¥þ¥@¬É¡C
|
¸ê®Æ
- Abramson JS, Wheeler JG,
Parce JW, et al. Suppression of endocytosis
in neutrophils by influenza A virus in vitro.
J Infect Dis 1986; 154: 456-63. Abstract:
http://amedeo.com/lit.php?id=3734493
- Achdout H, Arnon TI, Markel
G, et al. Enhanced recognition of human
NK receptors after influenza virus infection.
J Immunol 2003; 171: 915-23. Abstract: http://amedeo.com/lit.php?id=12847262
- Ahmed R, Gray D. Immunological
memory and protective immunity: understanding
their relation. Science 1996; 272: 54-60.
Abstract: http://amedeo.com/lit.php?id=8600537
- Akira S, Takeda K. Toll-like
receptor signalling. Nat Rev Immunol 2004;
4: 499-511. http://amedeo.com/lit.php?id=15229469
- Alford RH, Kasel JA, Gerone
PJ, Knight V. Human influenza resulting
from aerosol inhalation. Proc Soc Exp Biol
Med 1966; 122: 800-4. http://amedeo.com/lit.php?id=5918954
- Apisarnthanarak A, Kitphati
R, Thongphubeth K, et al. Atypical avian
influenza (H5N1). Emerg Infect Dis 2004;
10: 1321-4. Abstract: http://amedeo.com/lit.php?id=15324560
- Baigent SJ, McCauley JW.
Influenza type A in humans, mammals and
birds: determinants of virus virulence,
host-range and interspecies transmission.
Bioessays 2003; 25: 657-71. Abstract: http://amedeo.com/lit.php?id=12815721
- Beigel JH, Farrar J, Han
AM, et al. Avian influenza A (H5N1) infection
in humans. N Engl J Med 2005; 353: 1374-85.
http://amedeo.com/lit.php?id=16192482
- Belz GT, Smith CM, Kleinert
L, et al. Distinct migrating and nonmigrating
dendritic cell populations are involved
in MHC class I-restricted antigen presentation
after lung infection with virus. Proc Natl
Acad Sci U S A 2004; 101: 8670-5. Abstract:
http://amedeo.com/lit.php?id=15163797
- Bridges CB, Kuehnert MJ,
Hall CB. Transmission of influenza: implications
for control in health care settings. Clin
Infect Dis 2003; 37: 1094-101. Abstract:
http://amedeo.com/lit.php?id=14523774
- Brydon EW, Morris SJ, Sweet
C. Role of apoptosis and cytokines in influenza
virus morbidity. FEMS Microbiol Rev 2005;
29: 837-50. Abstract: http://amedeo.com/lit.php?id=16102605
- Buxton Bridges C, Katz JM,
Seto WH. Risk of influenza A (H5N1) infection
among health care workers exposed to patients
with influenza A (H5N1), Hong Kong. J Infect
Dis 2000; 181: 344-8. Abstract: http://amedeo.com/lit.php?id=10608786
- Cassidy LF, Lyles DS, Abramson
JS. Synthesis of viral proteins in polymorphonuclear
leukocytes infected with influenza A virus.
J Clin Microbiol 1988; 26: 1267-70. Abstract:
http://amedeo.com/lit.php?id=3045149
- Chan MC, Cheung CY, Chui
WH, et al. Proinflammatory cytokine responses
induced by influenza A (H5N1) viruses in
primary human alveolar and bronchial epithelial
cells. Respir Res 2005; 6: 135. Abstract:
http://amedeo.com/lit.php?id=16283933
- Chen W, Calvo PA, Malide
D, et al. A novel influenza A virus mitochondrial
protein that induces cell death. Nat Med
2001; 7: 1306-12. Abstract: http://amedeo.com/lit.php?id=11726970
- Cheung CY, Poon LL, Lau
AS, et al. Induction of proinflammatory
cytokines in human macrophages by influenza
A (H5N1) viruses: a mechanism for the unusual
severity of human disease? Lancet 2002;
360: 1831-7. Abstract: http://amedeo.com/lit.php?id=12480361
- Chotpitayasunondh T, Ungchusak
K, Hanshaoworakul W, et al. Human disease
from influenza A (H5N1), Thailand, 2004.
Emerg Infect Dis 2005; 11: 201-9. Abstract:
http://amedeo.com/lit.php?id=15752436
- Cox NJ, Kawaoka Y. Orthomyxoviruses:
Influenza. In: Topley & Wilson's Microbiology
and Microbial Infections, 9th ed., Collier
L, Balows A., Sussman M., eds., Edward Arnold,
London Vol.1, 1997: 385-433.
- Daniels RS, Douglas AR, Skehel
JJ, et al. Antigenic analyses of influenza
virus haemagglutinins with different receptor-binding
specificities. Virology 1984; 138: 174-7.
Abstract: http://amedeo.com/lit.php?id=6208680
- de Bree GJ, van Leeuwen EM,
Out TA, Jansen HM, Jonkers RE, van Lier
RA. Selective accumulation of differentiated
CD8+ T cells specific for respiratory viruses
in the human lung. J Exp Med 2005; 202:
1433-42. Abstract: http://amedeo.com/lit.php?id=16301748
- Flint SJ, Enquist LW, Racaniello
VR, Skalka AM. Principles of virology. Molecular
biology, pathogenesis, and control of animal
viruses. 2nd Edition, ASM Press,
Washington, DC, USA, 2004
- Gamblin SJ, Haire LF, Russell
RJ, et al. The structure and receptor binding
properties of the 1918 influenza hemagglutinin.
Science 2004; 303: 1838-42. Epub 2004 Feb
5. Abstract: http://amedeo.com/lit.php?id=14764886
- Garcia-Sastre A, Egorov A,
Matassov D, et al. Influenza A virus lacking
the NS1 gene replicates in interferon-deficient
systems. Virology 1998; 252: 324-30. Abstract:
http://amedeo.com/lit.php?id=9878611
- Garcia-Sastre A. Antiviral
response in pandemic influenza viruses.
Emerg Infect Dis 2006 (in press).
- Goto H, Kawaoka Y. A novel
mechanism for the acquisition of virulence
by a human influenza A virus. Proc Natl
Acad Sci U S A 1998; 95: 10224-8. Abstract:
http://amedeo.com/lit.php?id=9707628
- Guillot L, Le Goffic R,
Bloch S, et al. Involvement of toll-like
receptor 3 in the immune response of lung
epithelial cells to double-stranded RNA
and influenza A virus. J Biol Chem 2005;
280: 5571-80. Epub 2004 Dec 3. Abstract:
http://amedeo.com/lit.php?id=15579900
- Hall WJ, Douglas RG Jr,
Hyde RW, Roth FK, Cross AS, Speers DM. Pulmonary
mechanics after uncomplicated influenza
A infection. Am Rev Respir Dis 1976; 113:
141-8. Abstract: http://amedeo.com/lit.php?id=1247227
- Hayden FG, Fritz R, Lobo
MC, Alvord W, Strober W, Straus SE. Local
and systemic cytokine responses during experimental
human influenza A virus infection. Relation
to symptom formation and host defense. J
Clin Invest 1998; 101: 643-9. Abstract:
http://amedeo.com/lit.php?id=9449698
- Heath WR, Belz GT, Behrens
GM, et al. Cross-presentation, dendritic
cell subsets, and the generation of immunity
to cellular antigens. Immunol Rev 2004;
199: 9-26. Abstract: http://amedeo.com/lit.php?id=15233723
- Hemmes JH, Winkler KC, Kool
SM. Virus survival as a seasonal factor
in influenza and polimyelitis. Nature 1960;
188: 430-1. http://amedeo.com/lit.php?id=13713229
- Horner GJ, Gray FD Jr. Effect
of uncomplicated, presumptive influenza
on the diffusing capacity of the lung. Am
Rev Respir Dis 1973; 108: 866-9. http://amedeo.com/lit.php?id=4741881
- Hulse DJ, Webster RG, Russell
RJ, Perez DR. Molecular determinants within
the surface proteins involved in the pathogenicity
of H5N1 influenza viruses in chickens. J
Virol 2004; 78: 9954-64. Abstract: http://amedeo.com/lit.php?id=15331729
- Ishikawa E, Nakazawa M, Yoshinari
M, Minami M. Role of tumor necrosis factor-related
apoptosis-inducing ligand in immune response
to influenza virus infection in mice. J
Virol 2005; 79: 7658-63. Abstract: http://amedeo.com/lit.php?id=15919918
- Johansson BE, Bucher DJ,
Kilbourne ED. Purified influenza virus hemagglutinin
and neuraminidase are equivalent in stimulation
of antibody response but induce contrasting
types of immunity to infection. J Virol
1989; 63: 1239-46. Abstract: http://amedeo.com/lit.php?id=2915381
- Katz JM, Lim W, Bridges CB,
et al. Antibody response in individuals
infected with avian influenza A (H5N1) viruses
and detection of anti-H5 antibody among
household and social contacts. J Infect
Dis 1999; 180: 1763-70. http://amedeo.com/lit.php?id=10558929
- Katze MG, DeCorato D, Krug
RM. Cellular mRNA translation is blocked
at both initiation and elongation after
infection by influenza virus or adenovirus.
J Virol 1986; 60: 1027-39. Abstract: http://amedeo.com/lit.php?id=3023655
- Kondo S, Abe K. The effects
of influenza virus infection on FEV1 in
asthmatic children. The time-course study.
Chest 1991; 100: 1235-8. Abstract: http://amedeo.com/lit.php?id=1935277
- Lawrence CW, Braciale TJ.
Activation, differentiation, and migration
of naive virus-specific CD8+ T cells during
pulmonary influenza virus infection. J Immunol
2004; 173: 1209-18. Abstract: http://amedeo.com/lit.php?id=15240712
- Lawrence CW, Ream RM, Braciale
TJ. Frequency, specificity, and sites of
expansion of CD8+ T cells during primary
pulmonary influenza virus infection. J Immunol
2005; 174: 5332-40. Abstract: http://amedeo.com/lit.php?id=15843530
- Legge KL, Braciale TJ. Accelerated
migration of respiratory dendritic cells
to the regional lymph nodes is limited to
the early phase of pulmonary infection.
Immunity 2003; 18: 265-77. Abstract: http://amedeo.com/lit.php?id=12594953
- Levandowski RA, Gerrity
TR, Garrard CS. Modifications of lung clearance
mechanisms by acute influenza A infection.
J Lab Clin Med 1985; 106: 428-32. Abstract:
http://amedeo.com/lit.php?id=4045299
- Lipatov AS, Andreansky S,
Webby RJ, et al. Pathogenesis of Hong Kong
H5N1 influenza virus NS gene reassortants
in mice: the role of cytokines and B- and
T-cell responses. J Gen Virol 2005; 86:
1121-30. Abstract: http://amedeo.com/lit.php?id=15784906
- Little JW, Douglas RG Jr,
Hall WJ, Roth FK. Attenuated influenza produced
by experimental intranasal inoculation.
J Med Virol 1979; 3: 177-88. Abstract: http://amedeo.com/lit.php?id=479857
- Little JW, Hall WJ, Douglas
RG Jr, Mudholkar GS, Speers DM, Patel K.
Airway hyperreactivity and peripheral airway
dysfunction in influenza A infection. Am
Rev Respir Dis 1978; 118: 295-303. Abstract:
http://amedeo.com/lit.php?id=358877
- Mandelboim O, Lieberman
N, Lev M, et al. Recognition of haemagglutinins
on virus-infected cells by NKp46 activates
lysis by human NK cells. Nature 2001; 409:
1055-60. Abstract: http://amedeo.com/lit.php?id=11234016
- Matrosovich M, Tuzikov A,
Bovin N, et al. Early alterations of the
receptor-binding properties of H1, H2, and
H3 avian influenza virus hemagglutinins
after their introduction into mammals. J
Virol 2000; 74: 8502-12. Abstract: http://amedeo.com/lit.php?id=10954551
- Matrosovich MN, Matrosovich
TY, Gray T, Roberts NA, Klenk HD. Human
and avian influenza viruses target different
cell types in cultures of human airway epithelium.
Proc Natl Acad Sci U S A 2004; 101: 4620-4.
Abstract: http://amedeo.com/lit.php?id=15070767
- McCullers JA, Rehg JE. Lethal
synergism between influenza virus and Streptococcus
pneumoniae: characterization of a mouse
model and the role of platelet-activating
factor receptor. J Inf Dis 2002; 186: 341-50.
Abstract: http://amedeo.com/lit.php?id=12134230
- Mori I, Komatsu T, Takeuchi
K, Nakakuki K, Sudo M, Kimura Y. In vivo
induction of apoptosis by influenza virus.
J Gen Virol 1995; 76: 2869-73. Abstract:
http://amedeo.com/lit.php?id=7595397
- Olofsson S, Kumlin U, Dimock
K, Arnberg N. Avian influenza and sialic
acid receptors: more than meets the eye?
Lancet Infect Dis 2005; 5: 184-8. Abstract:
http://amedeo.com/lit.php?id=15766653
- Palladino G, Mozdzanowska
K, Washko G, Gerhard W. Virus-neutralizing
antibodies of immunoglobulin G (IgG) but
not of IgM or IgA isotypes can cure influenza
virus pneumonia in SCID mice. J Virol 1995;
69: 2075-81. Abstract: http://amedeo.com/lit.php?id=7884853
- Park CH, Ishinaka M, Takada
A, The invasion routes of neurovirulent
A/Hong Kong/483/97 (H5N1) influenza virus
into the central nervous system after respiratory
infection in mice. Arch Virol 2002; 147:
1425-36. Abstract: http://amedeo.com/lit.php?id=12111416
- Peiris JS, Yu WC, Leung
CW, et al. Re-emergence of fatal human influenza
A subtype H5N1 disease. Lancet 2004; 363:
617-9. http://amedeo.com/lit.php?id=14987888
- Piqueras B, Connolly J, Freitas
H, Palucka AK, Banchereau J. Upon viral
exposure myeloid and plasmacytoid dendritic
cells produce three waves of distinct chemokines
to recruit immune effectors. Blood 2005;
Abstract: http://amedeo.com/lit.php?id=16317096
- Renegar KB, Small PA Jr,
Boykins LG, Wright PF. Role of IgA versus
IgG in the control of influenza viral infection
in the murine respiratory tract. J Immunol
2004; 173: 1978-86. Abstract: http://amedeo.com/lit.php?id=15265932
- Sanz-Ezquerro JJ, Zurcher
T, de la Luna S, Ortin J, Nieto A. The amino-terminal
one-third of the influenza virus PA protein
is responsible for the induction of proteolysis.
J Virol 1996; 70: 1905-11. Abstract: http://amedeo.com/lit.php?id=8627716
- Schmitz N, Kurrer M, Bachmann
MF, Kopf M. Interleukin-1 is responsible
for acute lung immunopathology but increases
survival of respiratory influenza virus
infection. J Virol 2005; 79: 6441-8. Abstract:
http://amedeo.com/lit.php?id=15858027
- Shortman K, Liu YJ. Mouse
and human dendritic cell subtypes. Nat Rev
Immunol 2002; 2: 151-61. Abstract: http://amedeo.com/lit.php?id=11913066
- Silver ML, Guo HC, Strominger
JL, Wiley DC. Atomic structure of a human
MHC molecule presenting an influenza virus
peptide. Nature 1992; 360: 367-9. Abstract:
http://amedeo.com/lit.php?id=1448154
- Taubenberger JK. Influenza
virus hemagglutinin cleavage into HA1, HA2:
no laughing matter. Proc Natl Acad Sci U
S A 1998; 95: 9713-5. http://amedeo.com/lit.php?id=9707539
- To KF, Chan PK, Chan KF,
et al. Pathology of fatal human infection
associated with avian influenza A H5N1 virus.
J Med Virol 2001; 63: 242-6. Abstract: http://amedeo.com/lit.php?id=11170064
- Tran TH, Nguyen TL, Nguyen
TD, et al. Avian influenza A (H5N1) in 10
patients in Vietnam. N Engl J Med 2004;
350: 1179-88. http://amedeo.com/lit.php?id=14985470
- Treanor JJ. Influenza virus.
In: Mandell GL, Bennett JE, Dolin R, eds.
Mandell, Douglas, and Bennett's Principles
and Practice of Infectious Diseases. 6th
ed. Churchill Livingstone; 2004: 2060-2085.
- Tsitoura DC, Kim S, Dabbagh
K, Berry G, Lewis DB, Umetsu DT. Respiratory
infection with influenza A virus interferes
with the induction of tolerance to aeroallergens.
J Immunol 2000; 165: 3484-91. Abstract:
http://amedeo.com/lit.php?id=10975869
- Tumpey TM, Basler CF, Aguilar
PV, et al. Characterization of the reconstructed
1918 Spanish influenza pandemic virus. Science
2005; 310: 77-80. Abstract: http://amedeo.com/lit.php?id=16210530
- Uiprasertkul M, Puthavathana
P, Sangsiriwut K, et al. Influenza A H5N1
replication sites in humans. Emerg Infect
Dis 2005; 11: 1036-41. Abstract: http://amedeo.com/lit.php?id=16022777
- Ungchusak K, Auewarakul
P, Dowell SF, et al. Probable person-to-person
transmission of avian influenza A (H5N1).
N Engl J Med 2005; 352: 333-40. Abstract:
http://amedeo.com/lit.php?id=15668219
- Utell MJ, Aquilina AT, Hall
WJ, et al. Development of airway reactivity
to nitrates in subjects with influenza.
Am Rev Respir Dis 1980; 121: 233-41. http://amedeo.com/lit.php?id=7362132
- Weis W, Brown JH, Cusack
S, Paulson JC, Skehel JJ, Wiley DC. Structure
of the influenza virus haemagglutinin complexed
with its receptor, sialic acid. Nature 1988;
333: 426-31. Abstract: http://amedeo.com/lit.php?id=3374584
- Wiley JA, Cerwenka A, Harkema
JR, Dutton RW, Harmsen AG. Production of
interferon-gamma by influenza hemagglutinin-specific
CD8 effector T cells influences the development
of pulmonary immunopathology. Am J Pathol
2001a; 158: 119-30. Abstract: http://amedeo.com/lit.php?id=11141485
- Wiley JA, Hogan RJ, Woodland
DL, Harmsen AG. Antigen-specific CD8(+)
T cells persist in the upper respiratory
tract following influenza virus infection.
J Immunol 2001b; 167: 3293-9. Abstract:
http://amedeo.com/lit.php?id=11544317
- Wiley JA, Tighe MP, Harmsen
AG. Upper respiratory tract resistance to
influenza infection is not prevented by
the absence of either nasal-associated lymphoid
tissue or cervical lymph nodes. J Immunol
2005; 175: 3186-96. Abstract: http://amedeo.com/lit.php?id=16116209
- Wilson NS, Behrens GMN,
Lundie RJ, Systemic activation of dendritic
cells by TLR ligands or malaria infection
impairs cross cross-priming and anti-viral
immunity. Nat Immunol 2006 (in press)
- Woodland DL. Cell-mediated
immunity to respiratory virus infections.
Curr Opin Immunol 2003; 15: 430-5. Abstract:
http://amedeo.com/lit.php?id=12900275
- Woodland DL, Randall TD.
Anatomical features of anti-viral immunity
in the respiratory tract. Semin Immunol
2004; 16: 163-70. Abstract: http://amedeo.com/lit.php?id=15130500
- Woodland DL, Scott I. T
cell memory in the lung airways. Proc Am
Thorac Soc 2005; 2: 126-31. Abstract: http://amedeo.com/lit.php?id=16113480
- Yeldandi AV, Colby TV. Pathologic
features of lung biopsy specimens from influenza
pneumonia cases. Hum Pathol 1994; 25: 47-53.
Abstract: http://amedeo.com/lit.php?id=8314260
- Yen HL, Herlocher LM, Hoffmann
E, et al. Neuraminidase inhibitor-resistant
influenza viruses may differ substantially
in fitness and transmissibility. Antimicrob
Agents Chemother 2005; 49: 4075-84. Abstract:
http://amedeo.com/lit.php?id=16189083
- Yuen KY, Chan PK, Peiris
M, et al. Clinical features and rapid viral
diagnosis of human disease associated with
avian influenza A H5N1 virus. Lancet 1998;
351: 467-71. http://amedeo.com/lit.php?id=9482437
- Yuen KY, Wong SS. Human infection
by avian influenza A H5N1. Hong Kong Med
J 2005; 11: 189-99. Abstract: http://amedeo.com/lit.php?id=15951584
|
|
|
|
|