Chng 1

I CNG V MIN DCH HC

Tn gi ting Anh immunity (tnh min dch) c ngun gc t ting Latinh immunitas c ngha l min tr s co buc php lut dnh cho cc ngh s quc hi trong thi gian ng chc. Trong lch s, min dch c dng ch s khng mc bnh, m c th l cc bnh nhim trng. Trong c th, tt c cc t bo v phn t ho hc chu trch nhim v tnh min dch hp thnh h thng min dch, v ton b nhng p ng ca chng to ra i vi nhng cht l xm nhp vo c th c gi l p ng min dch. Chc nng sinh l ca h thng min dch l bo v mt c th chng li cc vi sinh vt gy bnh xm nhp vo c th . Tuy nhin, nhng cht l khng gy bnh xm nhp vo c th cng gy ra p ng min dch. Hn na, c ch bo v bnh thng cn c khi gy ra mt s thng tn cho c th. Do , ngi ta a ra mt nh ngha bao hm hn i vi tnh min dch l phn ng i vi cc cht l, bao gm c vi khun v cc i phn t nh protein, cc polysaccharide, khng k phn ng l sinh l hay bnh l. Min dch hc l mn hc nghin cu tnh min dch vi ngha rng ny i vi cc hot ng phn t v t bo xy ra sau khi cc vi sinh vt v i phn t xm nhp vo c th. Cc nh s hc k rng: Thucydides, mt ngi Hy Lp Athens, l ngi u tin vo th k th V trc Cng nguyn cp n tnh min dch chng li bnh nhim trng m lc c gi l bnh dch. Khi nim tnh min dch c l tn ti rt lu trc Trung Quc v ngi dn y c tp tc cho ngi dn ht cht bt lm t da ca ngi b u ma khi phng nga bnh ny. Cn min dch hc, vi t cch l mt mn hc hin i, li l mt ngnh khoa hc thc nghim, trong cc hin tng min dch c gii thch da trn nhng quan st thc nghim. Min dch hc, vi t cch l mt mn hc thc nghim, tin ho theo nng lc ca con ngi hiu bit v kim sot chc nng ca h thng min dch. Bng chng u tin trong lch s v nng lc ny l thnh cng ca Edward Jenner trong vic chng nga phng bnh u ma. Jenner l mt thy thuc ngi Anh, ng quan st thy rng nhng ngi vt sa b bnh u b v sau hi phc th khng bao gi mc bnh u ma na. Da vo nhn nh ny, ng ly dch t vt thng ca ngi b u b tim cho mt a tr 8 tui. a tr ny sau cho tip xc trc tip vi ngi bnh u ma th khng mc bnh v ng gi cch bo v ca mnh l "vaccination (chng nga) (ch vaccination bt ngun t ting

Latinh vacca ngha l con b ci) v cho xut bn quyn sch Vaccination vo nm 1798. T bin php phng bnh nhim trng ny pht trin rng ri v cho n nay n vn l phng php phng nga hiu qu nht i vi cc bnh nhim trng (Bng 1.1). Mt vn bn c ngha quan trng i vi ngnh Min dch hc l cng b ca T chc Y t Th gii nm 1980 rng bnh u ma l cn bnh u tin trn th gii b loi tr nh vo cng tc chng nga. T nhng nm 1960, chng ta c mt s chuyn bin trong hiu bit v h thng min dch v chc nng ca n. Cc tin b v k thut nui cy t bo (k c k thut sn xut khng th n dng), ho min dch, phng php DNA ti t hp, ng vt bin i gen, ... chuyn min dch hc t ch ch yu l cc hot ng m t thnh mt ngnh khoa hc m trong cc hin tng min dch c gii thch bng nhng thut ng sinh ho v cu trc. Trong chng ny chng ti trnh by nhng c im chung ca p ng min dch cng nh gii thiu nhng khi nim to nn nhng bc ngoc trong ngnh min dch hc hin i. Bng 1.1. Hiu qu ca vc-xin i vi mt s bnh nhim trng thng gp ti Hoa K
Bnh Bch hu S i Quai b Ho g Bi lit Rubella Un vn H. Znfluenza typ B Vim gan B S bnh nhn nm 2000 206.939 (1921) 894.134 (1941) 152.209 (1968) 265.269 (1934) 21.269 (1952) 57.686 (1969) 1.560 (1923) ~20.000 (1984) 26.611 (1985) S bnh nhn nm 2000 2 63 315 6.755 0 152 26 1.212 6.646 T l phn trm -99,99 -99,99 -99,99 -97,73 -100,00 -99,84 -98,44 -93,14 -75,03

1.1. Tnh min dch bm sinh v thu c S khng chng li vi sinh vt trong c th ban u l nhng phn ng ca h thng min dch bm sinh v sau l ca min dch thu c (Hnh 1.1, Bng 1.2). H min dch bm sinh (cn gi l min dch t nhin) bao gm cc c ch khng tn ti trong c th khi cha c nhim trng v sn sng p ng rt nhanh khi vi sinh vt xm nhp. Cc c ch ny ch yu phn ng chng li vi sinh vt ch khng phn ng vi cc vt l khng phi l vi sinh vt; ng thi chng phn ng theo mt c ch ging ht nhau khi vi sinh vt xm nhp ti i ti li. Cc thnh phn chnh ca min

dch bm sinh bao gm: (1) cc hng ro vt l v ho hc nh da, nim mc, cc cht khng khun c tit ra trn cc b mt ny; (2) cc t bo thc bo (t bo trung tnh, i thc bo) v t bo NK (t bo git t nhin); (3) cc protein trong mu, bao gm cc thnh phn ca h thng b th v cc cht trung gian khc ca phn ng vim; v (4) cc protein gi l cytokin c vai tr iu ho v phi hp cc hot ng ca t bo trong h min dch bm sinh. C ch hot ng ca h min dch bm sinh ch c hiu cho nhng cu trc chung ca tng nhm vi sinh vt v khng c hiu cho nhng khc bit tinh t trong tng nhm ny. H min dch bm sinh to ra nhng phn ng u tin chng li s xm nhp ca vi sinh vt.
Ngc vi h min dch bm sinh, c nhng p ng min dch khc c kch thch bi s tip xc vi vi sinh vt v to ra cng tng dn nu s tip xc ny c lp i lp li. Bi v dng p ng ny ch xut hin sau khi vi sinh vt xm nhp c th nn n c gi l min dch thu c. Tnh cht c bit ca p ng min dch thu c l tnh c hiu i vi tng phn t v kh nng nh khi phn t xm nhp tr li c th to ra mt p ng mnh hn nhiu so vi ln xm nhp u tin. H min dch thu c c kh nng nhn din v phn ng li vi nhiu vt l c bn cht nhim trng hoc khng nhim trng. Ngoi ra, n cn c kh nng tuyt vi trong vic phn bit s khc nhau rt nh gia cc vt l ny v v vy m n cn c gi l min dch c hiu. Cc thnh phn ca min dch thu c l t bo lymph v cc sn phm ca chng. Nhng cht l to ra p ng min dch c hiu hoc chu tc ng ca h min dch ny c gi l khng nguyn. Theo thi quen, cc thut ng p ng min dch v h thng min dch thng dng cho p ng min dch thu c, tr khi c nhng nhn mnh ring khc n min dch bm sinh.

Hnh 1.1. Min dch bm sinh v thu c

Cc c ch ca min dch t nhin cung cp sc khng ban u i vi nhim trng. p ng min dch thu c n mun hn vi s hot ho t bo lymph. Mc mnh hay yu ca p ng min dch bm sinh v thu c ph thuc tng loi nhim trng.

Bng 1.2. c im ca min dch bm sinh v min dch thu c

c im Tnh c hiu Tnh a dng Tnh nh Tnh khng p ng vi bn thn Hng ro l ho Cc protein mu T bo Bm sinh i vi cu to chung ca nhm vi sinh vt t Khng C Cc thnh phn tham gia Da, nim mc, cc ho cht khng khun B th Thc bo, t bo NK Thu c i vi khng nguyn c hoc khng nhim trng Rt nhiu C C

T bo lymph nim mc; khng th nim mc Khng th T bo lymph

Cc thnh phn ca p ng min dch bm sinh v thu c thng xen ln vi nhau trong mt c ch khng chung ca c th thng qua nhiu loi t bo v phn t. Ring min dch bm sinh c th gip c th thot khi s tn cng ca mt s vi sinh vt, nhng nhiu vi sinh vt gy bnh c kh nng vt qua hng ro min dch ny nn s loi tr chng cn n mt c ch khng mnh hn nhiu, l min dch thu c. C hai mi lin kt quan trng gia min dch bm sinh v thu c. Th nht, min dch bm sinh c kh nng kch thch p ng min dch thu c v nh hng n bn cht ca min dch thu c. p ng ca min dch thu c c s dng nhiu c ch hiu qu ca min dch bm sinh loi tr vi sinh vt v c kh nng tng cng hot ng khng khun ca min dch thu c. Min dch bm sinh v mt di truyn thuc h thng khng c nht ca c th ch, cn min dch thu c th mi c c nh tin ho v sau. ng vt c xng sng, sc khng ca c th ch chng li vi sinh c th ch yu c m trch bi min dch bm sinh, bao gm cc thc bo, v cc phn t protein lu ng trong mu. Min dch thu c bao gm t bo lymph v khng th, xut hin u tin loi xng sng c hm v cng bit ho i vi cc loi tin ho v sau. 1. 2. Cc kiu p ng min dch thu c C hai kiu p ng min dch thu c, l p ng th dch v p ng qua trung gian t bo. C hai kiu ny u c s tham gia ca rt nhiu thnh phn ca h thng min dch vi mc ch l loi tr nhiu loi vi sinh

vt khc nhau ra khi c th (Hnh 1.2). Min dch dch th c thc hin qua trung gian ca nhng phn t hin din trong mu v dch nim mc c tn l khng th, c sn xut bi t bo lymph B (cn gi l t bo B). Khng th c kh nng nhn din khng nguyn vi sinh vt, trung ho tnh gy bnh v tc ng ln vi sinh vt loi tr n qua nhiu c ch hiu qu khc nhau. Min dch dch th l c ch khng ch yu chng li cc vi sinh vt ngoi bo cng nh c t ca chng theo c ch khng th lin kt vi cc vi sinh vt hoc c t xc tin vic loi tr. Bn thn khng th l nhng phn t c chuyn mn ho, nhng tup khng th khc nhau c th to ra nhiu c ch loi b khng nguyn khc nhau. Mt s tup khng th c kh nng xc tin hot ng thc bo, mt s khc li kch thch t bo bch cu sn xut ra cc cht trung gian ca phn ng vim. Min dch qua trung gian t bo (cn gi l min dch t bo) l kiu p ng c thc hin qua trung gian ca t bo lymph T (cn gi l t bo T). Cc vi sinh vt ni bo nh virus v mt s vi khun c kh nng sng v nhn ln trong i thc bo cng nh mt s t bo ch khc, v th chng khng chu tc ng trc tip ca khng th lu ng trong mu. S khng chng li nhng vi sinh vt kiu ny l chc nng ca min dch t bo.

Ngn chn nhim trng v loi b cc vi sinh vt ngoi bo

Hnh 1.2. Cc kiu min dch thu c

Trong min dch dch th, t bo B tit ra khng th ngn chn nhim trng v loi b cc vi khun ngoi bo. Trong min dch qua trung gian t bo, t bo T hot ha i thc bo tiu dit vi khun b n vo bn trong t bo ny hoc t bo T gy c trc tip tiu dit t bo b nhim khun.

Min dch bo v chng li mt vi sinh vt c th c to ra nh kch thch ca vi sinh vt hoc nh truyn khng th hoc t bo lymph c hiu t bn ngoi vo (Hnh 1.3). Cch thc to khng th qua kch thch trc tip vi vt l c gi l min dch ch ng v c th tip xc vi vt l ng vai tr ch ng trong vic p ng vi khng nguyn. Nhng c th hoc t bo lymph cha tng c tip xc vi mt khng nguyn no c gi l nguyn vn hay nguyn (naive). Cn nhng c th c tip xc vi mt khng nguyn vi sinh vt no ri v sau c bo v chng li nhng ln tip xc khc c gi l min nhim (immune).

Hnh 1.3. Min dch ch ng v th ng

Min dch ch ng c to ra khi c th ch tip xc vi vi sinh vt hoc khng nguyn vi sinh vt, trong khi min dch th ng c vay mn nh truyn khng th hay t bo lymph T c hiu. C hai loi u to ra sc khng i vi vi sinh vt nhng ch c min dch ch ng l c tnh nh min dch.

Ngi ta cng c th mang tnh min dch n cho mt c th bng cch truyn huyt thanh hoc t bo lymph t mt c th khc c gy min dch. Cch lm ny c gi l truyn min dch th ng, thng hay thc hin trn ng vt th nghim. C th nhn sau s c tnh min dch chng li khng nguyn tng ng mc d cha ln no tip xc vi khng nguyn ny. Do kiu min dch ny c gi l min dch th ng. Gy min dch th ng l mt phng php hu ch cung cp sc khng nhanh, khng phi ch cho n khi min dch ch ng xut hin. Mt v d ca min dch th ng l truyn khng th t m sang con trong thi k bo thai gip cho a tr chng li nhim trng trong thi k ch i min dch ch ng ca tr hnh thnh. Ngi ta cng dng phng php min dch th ng chng li c t vi khun gy cht ngi (v d c t un vn) bng cch truyn khng th t con vt c gy min dch bi vi sinh vt . K thut truyn min dch th ng (hay cn gi l to min dch vay mn) cng c th thc hin vi nhng t bo v phn t khc nhau min l chng c nng lc min dch c hiu. Tht ra, thut ng min dch dch th (humoral immunity) ban u c nh ngha nh mt kiu min dch c th truyn c sang cho con vt cha nhim bng cht dch trong mu c cha khng th v khng c t bo (tc l huyt thanh hoc huyt tng m t c gi l th dch - humor). Cng vy, min dch qua trung gian t bo (cell-mediated immunity) c nh ngha l mt dng min dch c th truyn sang cho c th cha nhim di dng t bo (lymph T) ch khng phi dch th. Nm 1890, Emil von Behring v Shibasaburo Kitasato trnh din th nghim u tin v min dch dch th. H cho thy rng, nu huyt thanh ca con vt khi bnh bch hu c truyn cho con vt cha nhim th con vt ny s c kh nng khng c hiu i vi bnh bch hu. Thnh phn hiu lc trong huyt thanh lc c gi l khng c t v n trung ho tc dng bnh l ca c t bch hu. u nhng nm 1890, Karl Landsteiner v cc nh nghin cu khc chng minh rng khng phi ch c c t m nhng cht khng c ngun gc vi sinh vt khc cng c th to ra p ng min dch dch th. T cc th nghim , ngi ta a ra mt thut ng mi l khng th (antibody) ch thnh phn protein huyt thanh to ra tnh min dch dch th. Nhng cht lin kt vi khng th v to ra s sn xut khng th c gi l khng nguyn (antigen). Nm 1900, Paul Ehrlich a ra mt l thuyt mi v tnh c hiu ca phn ng khng nguyn khng th, m nhng bng chng thc nghim cho l thuyt ny ln lt c a ra trong sut 50 nm k t khi c pht hin ca Lansteiner. L thuyt ca Ehrlich v s khp nhau v mt l ho ca khng nguyn v khng th rt c gi tr vo thi k u ca min dch hc. S nhn mnh v khng th trong l thuyt ny dn n s tha nhn

chung tm quan trng ca min dch dch th, min dch c trung gian bi nhng cht hin din trong cc dch c th. L thuyt t bo v min dch c Metchnikoff a ra. Trnh din ca ng v s thc bo xy ra xung quanh chic gai hng c m vo c th trong sut ca u trng sao bin c xut bn nm 1893. y c l l bng chng thc nghim u tin v vai tr p ng t bo i vi vt l xm nhp vo c th. Cc quan st ca Sir Almroth Wright vo u nhng nm 1900 cho thy rng, trong huyt thanh min dch c nhng yu t thc y s thc bo vi khun bng cch bc xung quanh vi khun, iu ny lm ngi ta tin rng khng th chun b vi khun thc bo d bt gi hn, qu trnh ny c gi l opsonin ho. Nhng ngi theo trng phi t bo ny khng chng minh c rng tnh c hiu ca min dch i vi vi sinh vt cng th hin c qua min dch t bo. L thuyt t bo trong min dch c khng nh vo nhng nm 1950, khi George Mackaness chng t rng, s khng i vi mt loi vi sinh vt ni bo, con Listeria monocytogenes, c th vay mn bng cch truyn t bo ch khng phi truyn huyt thanh. Chng ta bit rng tnh c hiu ca min dch t bo l do lymph, t bo ny c chc nng lm nhc trng iu khin cc t bo khc nh i thc bo nhm loi b vi sinh vt. Trn lm sng, tnh min dch i vi mt vi sinh vt b nhim trc y c th o c mt cch gin tip bng cch nh lng cc sn phm ca min dch hin din trong c th (v d khng th c hiu trong huyt thanh) hoc chit xut cc cht t c th vi sinh vt v nh gi phn ng ca c th i vi cc cht ny. Mt phn ng ca c th i vi mt khng nguyn vi sinh vt no ch xy ra nu trc c th tip xc vi khng nguyn ny ri; khi c th c gi l c mn cm i vi khng nguyn . Ngi ta cho rng cc c th c mn cm c kh nng to ra p ng min dch bo v i vi vi sinh vt . 1.3. Cc c im chnh ca p ng min dch thu c Tt c p ng dch th v t bo i vi vt l c nhiu tnh cht c bn phn nh tnh cht ca t bo lymph lm trung gian cho phn ng ny (Bng 1.3).
Bng 1.3. Cc c im chnh ca p ng min dch thu c
c im c hiu a dng Nh ngha chc nng m bo cc khng nguyn khc nhau to ra p ng c hiu ring cho chng Cho php h thng min dch p ng c nhiu loi khng nguyn Dn n p ng mnh hn i vi khng nguyn

Chuyn mn ho T gii hn Khng ph n ng v i b n thn

tng tip xc To ra p ng ti u chng li nhiu loi vi sinh vt khc nhau Cho php h thng min dch p ng c vi cc khng nguyn mi xm nhp Ngn nga cc tn thng i vi c th ch trong sut qu trnh phn ng vi khng nguyn l

1.3.1. Tnh c hiu v a dng p ng min dch c hiu cho tng khng nguyn khc nhau v c ngay cho tng thnh phn cu trc ca khng nguyn nh protein, polysaccharide hoc i phn t (Hnh 1.4). Nhng thnh phn ny ca khng nguyn c gi l quyt nh khng nguyn hay epitop. Tnh c hiu ny c c l nh trn mng ca cc t bo lymph ring l c nhng th th ring nhn din nhng cu trc khng nguyn khc nhau. Trong c th c gy min dch c nhiu cln t bo lymph vi tnh c hiu khc nhau tn ti, chng c th nhn din v p ng li tt c khng nguyn ngoi lai. Khi nim ny l nn tng ca l thuyt chn cln m chng ta s cp n v sau ny.

Hnh 1.4. Tnh c hiu, nh, v t gii hn ca p ng min dch

Khng nguyn X v Y to ra s sn xut cc khng th khc nhau (tnh c hiu). p ng ln th hai i vi khng nguyn X th nhanh hn v mnh hn (nh). Mc khng th gim dn theo thi gian sau mi ln gy min dch (t gii hn). Ngi ta cng thy c hin tng tng t th ny i vi min dch t bo.

Tng s tnh c hiu ca t bo lymph trong mt c th l mt con s cc k ln v c gi l kho lymph (lymphocyte repertoire). Ngi ta c tnh rng h thng min dch ca mt c th c th phn bit t 107 n 109 quyt nh khng nguyn khc nhau. iu ny to nn tnh a dng ca kho lymph. Mt h qu c th thy l cc din kt hp khng nguyn ca khng th v th th khng nguyn trn t bo lymph cng c cu trc rt a dng tng ng vi kho lymph ny. 1.3.2. Nh min dch S tip xc ca h min dch vi khng nguyn l lm tng cng p ng vi khng nguyn khi n xm nhp c th cc ln sau. p ng cc ln lp li v sau i vi mt khng nguyn c gi l p ng min dch th cp. p ng ny thng nhanh hn, mnh hn v khc v cht so vi p ng s cp khi c th tip xc khng nguyn ln u tin (xem Hnh 1.4). Nh min dch c c mt phn l do c mi ln tip xc vi c th th khng nguyn m rng cln lymph c hiu cho khng nguyn . ng thi, s kch thch t bo lymph nguyn vn ca khng nguyn to ra cc t bo nh tn ti lu di. T bo nh c tnh cht c bit lm cho chng loi b khng nguyn hiu qu hn so vi t bo lymph nguyn vn. V d, t bo lymph B nh sn xut khng th lin kt vi khng nguyn vi i lc mnh hn so vi t bo B cha tng tip xc vi khng nguyn . T bo T nh cng c kh nng tr v ni nhim trng nhanh hn t bo T nguyn vn (tc cha tng tip xc khng nguyn). 1.3.3. Chuyn mn ho H thng min dch p ng mt cch c bit v khc nhau i vi tng vi sinh vt sao cho c th to hiu qu ti a cho c ch khng. Nh vy, min dch dch th v min dch t bo c hnh thnh mt cch khc nhau di s kch thch ca nhng loi vi sinh vt khc nhau hoc cc giai on nhim trng khc nhau (ngoi bo v ni bo) ca mt vi sinh vt bo v c th ch chng li loi vi sinh vt vo giai on nhim trng . V ngay trong tng kiu min dch dch th hay t bo th bn cht ca khng th hay t bo T c to ra cng khc nhau tuy loi vi sinh vt kch thch. 1.3.4. T gii hn Tt c p ng min dch bnh thng s phai nht dn theo thi gian tr li h min dch trng thi ngh ban u, tnh trng ny gi l hng nh ni mi (homeostasis). Tnh trng cn bng dch th c duy tr ch yu l v p ng min dch c khi ng bi khng nguyn v nhm n

loi tr khng nguyn, v nh vy tc l loi tr nguyn nhn gy hot ho t bo lymph. Ngoi ra, khng nguyn v p ng min dch cn kch thch c ch iu ho nhm c ch chnh p ng ny. 1.3.5. Khng phn ng vi bn thn Mt trong nhng tnh cht quan trng ca h min dch ca ngi bnh thng l kh nng nhn bit, p ng v loi b khng nguyn l (khng phi ca bn thn) v khng phn ng li gy hi cho c th (bn thn). Tnh cht khng p ng min dch ny cn c gi l dung np. Dung np i vi khng nguyn bn thn, tc t dung np, c duy tr bi nhiu c ch. Nhng c ch ny bao gm loi b t bo lymph c mang th th c hiu cho khng nguyn bn thn v cho php t bo lymph tiu dit cc khng nguyn t thn c kh nng to ra phn ng chng li bn thn. Nhng bt thng v kh nng t dung np c th dn n p ng min dch i vi khng nguyn bn thn (t khng nguyn) v hnh thnh cc bnh t min. Cc tnh cht trn y ca min dch thu c rt cn thit duy tr chc nng khng bnh thng ca c th ch. 1.4. Cc thnh phn t bo ca h thng min dch thu c Cc t bo chnh ca h min dch l t bo lymph, t bo trnh din khng nguyn, v t bo hiu qu. T bo lymph l nhng t bo c kh nng nhn din mt cch c hiu khng nguyn l v to phn ng chng li chng. Do vy, lymph bo l t bo trung gian ca c min dch dch th v min dch t bo. C nhiu tiu qun th t bo lymph khc nhau v c cch nhn din khng nguyn ln chc nng ca chng (Hnh 1.5). T bo lymph B l t bo duy nht c th sn xut khng th. Chng nhn din khng nguyn ngoi bo (k c khng nguyn trn b mt t bo) v bit ho thnh t bo tit khng th, do chng tc dng nh t bo trung gian ca min dch dch th. T bo lymph T nhn din khng nguyn ca vi sinh vt ni bo v c chc nng tiu dit nhng vi sinh vt ny hoc nhng t bo b nhim trng. Th th khng nguyn ca chng l nhng phn t mng khc vi khng th nhng c cu trc lin quan. T bo T c tnh c hiu rt cht ch i vi khng nguyn. Chng ch nhn din nhng phn t peptid gn vi mt protein bn thn c m ho bi nhng gen trong phc h ha hp m ch yu (MHC) v c th hin trn b mt ca nhng t bo khc. Nh vy, t bo T nhn din v phn ng vi khng nguyn gn trn b mt t bo ch khng phi khng nguyn ho tan. T bo T c nhiu nhm mang chc nng khc nhau. c bit nhiu nht l t bo T gip ,

T gy c. Khi p ng vi khng nguyn, t bo T gip tit ra nhng protein gi l cytokin c chc nng kch thch s tng sinh v bit ho ca t bo T v mt s t bo trong c t bo B, i thc bo v cc bch cu khc. T bo T gy c git cc t bo sn xut ra khng nguyn l nh cc t bo b nhim virus hay nhng vi khun ni bo khc. Mt s t bo T c gi l T iu ho c chc nng c ch p ng min dch. Bn cht v vai tr sinh l ca t bo T iu ho cha c bit y . C mt nhm t bo lymph th ba l t bo git (NK), y l nhng t bo tham gia vo h thng min dch bm sinh chng li nhim trng virus v cc vi sinh vt ni bo khc. S khi ng v pht trin p ng min dch thu c bao gi cng i hi khng nguyn phi c bt gi v trnh din cho t bo lymph. T bo chu trch nhim lm vic ny c gi l t bo trnh din khng nguyn (APC). T bo trnh din khng nguyn c chuyn mn ho cao nht l t bo hnh sao (dendritic), chng bt gi nhng vi sinh vt t bn ngoi xm nhp vo, vn chuyn nhng khng nguyn ny n cc c quan lymph v trnh din khng nguyn cho nhng t bo T khi ng p ng min dch. S hot ho t bo lymph bi khng nguyn dn n s hnh thnh nhiu c ch loi b khng nguyn. S loi b khng nguyn i hi s tham gia ca nhng t bo gi l t bo hiu qu. T bo lymph hot ho, thc bo n nhn, v mt s bch cu khc c th lm chc nng t bo hiu qu trong nhng p ng min dch khc nhau. T bo lymph v nhng t bo h tr ca h min dch c tp trung ti cc c quan lymph; chng tng tc vi nhau to ra p ng min dch. T bo lymph cng hin din trong mu. T mu chng c th theo mu tun hon n cc m lymph v cc v tr ngoi bin ni khng nguyn thng xm nhp loi tr chng.

Hnh 1.5. Cc tiu qun th lymph bo

Lymph bo B nhn din khng nguyn ho tan v pht trin thnh t bo tit khng th. Lymph bo T gip nhn din khng nguyn trn b mt ca t bo trnh din khng nguyn v tit ra cytokin kch thch cc c ch ca phn ng min dch v vim. Lymph bo T gy c nhn din khng nguyn trn t bo nhim trng v git nhng t bo ny. T bo NK (git t nhin) dng nhng th th (cha c xc nh c hon ton) nhn din v git t bo ch, v d t bo nhim trng.

1.5. Cc giai on ca p ng min dch thu c Qu trnh p ng min dch thu c c th chia thnh nhiu giai on khc nhau: nhn din khng nguyn, hot ho t bo lymph, v giai on hiu qu (loi tr khng nguyn). Sau l s tr li hng nh ni mi v duy tr tnh nh min dch (Hnh 1.6). Tt c p ng min dch u c khi u bng nhn din khng nguyn c hiu. S nhn din ny dn n hot ho t bo lymph v sau l hnh thnh cc c ch hiu qu lm chc nng loi b khng nguyn. Sau khi khng nguyn c loi b, p ng min dch du i v tr li tnh trng hng nh ni mi.

Hnh 1.6. Cc giai on ca p ng min dch thu c

Ba giai on u c tn l nhn din khng nguyn, hot ho t bo lymph v hiu qu (loi b khng nguyn). p ng tt dn v cc t bo lymph c khng nguyn kch thch s cht dn do hin tng cht lp trnh (apoptosis), nhng t bo c hiu khng nguyn cn li l t bo nh. Thi gian ca mi giai on thay i tu theo bi cnh p ng. Trc y tng trng cho cng ca p ng. M hnh ny p dng cho c min dch dch th v min dch t bo.

1.5.1. Nhn din khng nguyn Mi c th s hu mt lng t bo lymph vi rt nhiu cln khc nhau. Mi cln mang sn nhng yu t nhn din v p ng vi mt quyt nh khng nguyn nht nh. Khi khng nguyn xm nhp c th n tm n cln lymph tng ng v hot ho n (Hnh 1.7). Quan nim c bn ny c gi l thuyt chn cln (clonal selection hypothesis), ln u tin c Niels Jerne a ra vo nm 1955 v c Macfarlane Burnet lm sng t vo nm 1957. y l gi thuyt gii thch ti sao h thng min dch li c th p ng vi mt s lng rt ln cc loi khng nguyn khc nhau. Theo gi thuyt ny, cc cln lymph c hiu khng nguyn c sn trong c th trc khi tip xc vi khng nguyn. Nhng t bo trong cng cln mang th th khng nguyn ging ht nhau v khc vi t bo ca cln khc. Mc d rt kh xc nh gii hn trn ca s lng quyt nh khng nguyn m h min dch ca mt c th ng vt c v c th nhn din c, nhng ngi ta thng cho rng con s ny l vo khong t 107 n 109. y l con s c lng hp l i vi s lng protein th th khng nguyn c sn xut v do ngi ta cho rng s lng cln t bo lymph hin din trong c th cng nh th. Khng nguyn l s tng tc vi cln t bo lymph c hiu cho khng nguyn tn ti sn trong m lymph to ra p ng min dch.

Hnh 1.7. Thuyt chn cln

Mi khng nguyn (x hoc y) chn mt cln lymph c hiu c sn v kch thch s tng sinh, bit ho ca cln . S ny ch trnh by qu trnh lymph B pht trin thnh t bo hiu qu v tit ra khng th, nhng nguyn l ny cng p dng cho c t bo T.

Nhng nguyn l c bn ca thuyt chn cln dn c chng minh mt cch thuyt phc qua nhiu th nghim v to nn nn tng cho quan nim hin nay v s nhn din khng nguyn ca t bo lymph c hiu. 1.5.2. Hot ho t bo lymph S hot ho t bo lymph i hi 2 tn hiu khc nhau: tn hiu th nht l khng nguyn v tn hiu th hai l cc sn phm vi sinh vt hoc l cc thnh phn ca p ng min dch bm sinh i vi vi sinh vt (Hnh 1.8). tng ny c gi l thuyt hai tn hiu i vi s hot ho lymph bo. Yu cu v khng nguyn (tc tn hiu 1) nhm m bo tnh c hiu ca p ng min dch. Cn yu cu v kch thch ph do sn phm vi khun hoc ca p ng bm sinh i vi vi khun nhm m bo phn ng ch c to ra khi cn thit (tc chng vi khun hoc cht c hi khc) ch khng chng li cc cht v hi bao gm khng nguyn bn thn.

Hnh 1.8. Yu cu hai tn hiu i vi hot ho lymph bo

S nhn din khng nguyn ca lymph bo cung cp tn hiu 1 cho s hot ho, v cc thnh phn ca vi sinh vt hoc cc cht to ra trong qu trnh p ng min dch bm sinh cung cp tn hiu 2. Trong hnh ny, t bo lymph l t bo B, nhng i vi t bo T cng c nguyn l nh vy.

p ng ca lymph bo i vi khng nguyn v tn hiu th hai bao gm s tng hp cc protein mi, tng sinh t bo, v bit ho thnh t bo hiu qu v t bo nh. 1.5.3. Giai on hiu qu ca p ng min dch: loi b khng nguyn Trong sut giai on hiu qu ca p ng min dch, cc lymph bo c khng nguyn hot ho s to ra nhng chc nng hiu qu tin n vic loi b khng nguyn. Khng th loi b khng nguyn ngoi bo v t bo T loi b khng nguyn ni bo. Chc nng ny ca khng th v t bo T thng yu cu s tham gia ca cc t bo hiu qu khc khng thuc h lymph v c c ch khng ca min dch bm sinh. Nh vy, cng nhng c ch min dch bm sinh hot ng nh phng tuyn u tin nhng v sau li cn tham gia vo phng tuyn th hai ca min dch thu c loi b khng nguyn ra khi c th. Tht ra, nh ni trn, mt chc nng quan trng ca p ng min dch thu c l nhm tng cng c ch hiu qu ca min dch bm sinh v hng nhng c ch hiu qu ny vo cc m hoc t bo cha khng nguyn l. 1.5.4. Tnh hng nh ni mi: gim dn p ng min dch

Vo cui p ng min dch, h thng min dch tr li trng thi ngh c bn do phn ln cc t bo tin thn (progeny) ca lymph b khng nguyn kch thch cht do hin tng cht lp trnh (apoptosis). Cht lp trnh l mt dng cht sinh l c chun b trc, trong nhn t bo b c li v v ra tng mnh, mng bo tng ni bt, khng cn s tch bit ca lp lipid mng v t bo cht nhanh chng b thc bo m cc cht ni bo khng cn b gii phng ra ngoi (qu trnh cht ny ngc vi kiu cht hoi t, trong nhn v mng bo tng b phn gii v cc cht ni bo b v ra ngoi to ra mt phn ng vim ti ch). Mt lng ln t bo lymph b khng nguyn kch thch s cht i theo kiu lp trnh. Gii thch iu ny, ngi ta cho rng c l do s tn ti ca lymph bo ph thuc vo khng nguyn v cc yu t pht trin do khng nguyn khi ng nn khi p ng min dch loi b ht khng nguyn th t bo lymph khng cn nhn c nhng kch thch cn thit cho s sng.