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Chng 1

KHI NIM V MIN DCH HC


I. M u
Sinh vt trong mi trng sng buc phi trao i tch cc vi mi trng tn ti, pht trin v sinh sn. S trao i ny l cn thit tuy nhin n cng thng xuyn mang li cc nguy c c hi cho sinh vt bi v mi trng sng lun cha y nhng tc nhn gy bnh, c bit l cc tc nhn vi sinh vt. that khi cc nguy c ny, trong qu trnh tin ha sinh vt hnh thnh v hon thin dn cc h thng-chc nng bo v cho chnh mnh, mt trong cc h thng l h thng min dch. Min dch hc l mn hc nghin cu nhng hot ng sinh l cng nh bnh l ca h thng min dch. H thng min dch c th chia lm h thng min dch khng c hiu (MDKH) v h thng min dch min dch c hiu (MDH). Thut ng min dch khng c hiu cn c cc tn gi khc nh min dch t nhin, min dch bm sinh. Thut ng min dch c hiu cng c cc tn gi khc nh min dch thu c, min dch thch nghi. Trong lch s tin ha ca h min dch, cc p ng min dch khng c hiu c hnh thnh rt sm v pht trin n lp ng vt c xng sng th cc p ng min dch c hiu mi c hnh thnh. thc hin c chc nng bo v cho c th, hai loi p ng min dch trn hp tc, b tc, khuych i v iu ha hiu qu ca p ng min dch.

II. H thng min dch khng c hiu


H thng min dch khng c hiu l hng ro bo v u tin ca c th chng li s xm nhp ca vi sinh vt v cc yu t l khc. Chng bao gm cc thnh phn khng chuyn bit (cn mt s chc nng khc) v chuyn bit thc hin chc nng min dch. 1. Cc c ch khng chuyn bit tham gia vo p ng MDKDH 1.1. C ch c hc S nguyn vn ca da nim mc l hng ro bo v, ngn chn s xm nhp ca vi sinh vt. Mi s tn thng nh trong bng, rch da hoc cc th thut tim truyn u lm tng nguy c nhim trng. Ngoi ra cn c cc hot ng c hc ca lp tim mao nhy ca h thng ng h hp trn nhm loi b v tng kh cc vi khun, cht thi ra ngoi. Cc phn x ho, ht hi cng cho kt qu nh vy. S lu thng v nhu ng ca ng tiu ha, ng tit niu, ng mt ngn cn s pht trin ca vi khun. 1.2. C ch ha hc Trong cc dch tit t nhin c cha cc ha cht c tc dng dit khun khng chuyn bit. V d cc axit bo trong tuyn b, pH thp ca dch m o hn ch s tng trng ca vi khun. toan cao trong dch v c kh nng loi b hu ht cc vi khun. 1.3. C ch sinh hc Trn b mt da, ng tiu ha thng xuyn c mt cc vi khun cng sinh khng gy bnh. Cc vi khun ny ngn cn s pht trin ca cc vi khun gy bnh bng cch cnh tranh cht dinh dng, tit ra cc cht km khun nh colicin i vi vi khun ng rut.

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Bng 1.1. H thng p ng min dch khng c hiu (khng chuyn bit)

2. Cc c ch chuyn bit tham gia vo p ng MDKDH 2.1. Cc thnh phn dch th 2.1.1. Lysozym L enzym c trong nc mt, nc bt, nc mi, da (trong huyt thanh hm lng rt thp). Lysozym c kh nng ct cu ni phn t ca mng vi khun, do c kh nng lm ly gii mt s vi khun gram dng. Cc vi khun gram m nh c v bc ngoi l peptidoglican nn khng b ly gii trc tip. Tuy nhin khi v ngoi b thng do tc dng ca b th th lysozym s hip lc tn cng mng vi khun. 2.1.2. Cc protein vim L cc protein c to ra trong pha cp ca phn ng vim nh CRP (C-Reactive Protein, 1 antitrypsin, 1antichymotrypsin, haptoglobin). Trong CRP c sn xut sm nht v c th tng gp 100 ln so vi bnh thng. V vy trong lm sng s dng nh lng CRP huyt thanh chn on v theo di vim ni chung. 2.1.3. Interferon (IFN) L mt nhm cc polypeptid c sn xut do cc t bo nhim vi rut tit ra (Interferon - v ) hay do cc t bo lympho T hot ha (Interferon-). Cc interferon c nhiu hot tnh sinh hc nh cn tr s xm nhp v s nhn ln ca vi rut, km hm s tng sinh ca ca mt s t chc u, c kh nng hot ha cc i thc bo v tng biu l cc khng nguyn ha hp m gip cho qu trnh nhn din khng nguyn ca t bo lympho T. Cc hot tnh ny khng c tnh c hiu vi khng nguyn, c th xy ra vi tt c loi vi rut nn interferon c xp vo h thng min dch khng c hiu. 2.1.4. B th (complement, C) H thng b th bao gm khong 25 loi protein huyt thanh tham gia vo c ch khng t nhin ca c th v c p ng min dch c hiu. Trong huyt thanh b th c sn xut di dng khng hot ng v c hai con ng hot ha b th: - Con ng c in: bt u t C1q v khi ng bi phc hp khng nguyn v khng th (KN-KT), trong khng th thuc loi IgG hoc IgM. - Con ng tt: khng ph thuc vo c ch min dch c hiu (khng cn c s hin din ca khng th v khi ng t C3). Cc vi sinh vt v nhiu cht khc c th li hot ha b th theo con ng tt nh trc khun Gram (+) hay gr (-), vi rut Dengue (st xut huyt, nm, k sinh trng, v mt s cht khc nh polysaccharid vi khun (vi khun lao, ph cu).

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2.2. Cc thnh phn t bo 2.2.1. Cc bch cu ht

Chim a s trong bch cu mu ngoi vi (60-70%), c i sng ngn (3-4 ngy). Trong nhm ny bch cu ht trung tnh chim a s v tham gia tch cc vo phn ng vim, chng c kh nng thc bo v trong bo tng c cc ht cha nhiu enzym tiu m, enzym thy phn nh myeloperoxydase, elastase, cathepsin G, hydrolase, lactoferin, collagenase, lysozym. Cc bch cu i toan c vai tr trong khng i vi k sinh trng, phn ng d ng ti ch. Cc bch cu i kim c vai tr tng t nh t bo mast do trn b mt t bo c cc th th i vi mnh Fc ca khng th IgE (FcR). Cc t bo c hot ha khi c hin tng bt cu (lin kt cho) gia cc IgE v khng nguyn c hiu gii phng v tng hp cc hot cht trung gian nh histamin, serotonin, leucotrien. 2.2.2. Bch cu n nhn Cc t bo ny c ngun gc t ty xng lu hnh trong h tun hon, nhng khi xm nhp vo cc t chc th bit ha thnh cc i thc bo vi cc tn gi khc nhau nh t bo Kupffer, t bo bch tuc, t bo xe ngn tay. Chng c kh nng thc bo rt mnh nn c vai tr trong dn dp cc vt l, cc t chc b ph hy, t bo gi ci. Kh nng thc bo ca cc bch cu ht trung tnh , bch cu n nhn / thc bo ph thuc vo s lin kt gia vi sinh vt i vi cc th th b mt ca t bo nh th th i vi C3b. Mi khi vi sinh vt c nhp ni bo trong cc ti, tip theo l s ha mng vi cc th tiu bo. Qu trnh dit khun xy ra theo hai phng thc ph thuc oxy hoc khng ph thuc oxy to ra cc sn phm nh: O2-, H2O2, OCl-, OH- v 1O2, lysozym, lactoferin, cathepsin G, enzym tiu m. Ngoi ra cc t bo n nhn/i thc bo cn tham gia ch ng p ng min dch c hiu bng cch bit ha thnh cc t bo c chc nng trnh din KN cho cc t bo lympho T v tit ra cc cytokin (IL1, TNF,...) m u cho p ng min dch c hiu. 2.2.3. T bo NK (natural killer cells) C mt trong tun hon ngoi vi v c t l t 5-15% cc t bo lympho. V hnh thi th n ging t bo lympho nhng c nhng ht ln trong bo tng, t bo NK khng c cc du n (marker) b mt ca t bo lympho T v t bo lympho B. T bo NK c kh nng dit cc t bo ung th, t bo nhim vi rut m khng cn c mn cm trc v khng b gii hn bi phc hp ha hp m (khng c tnh c hiu).

III. H thng min dch c hiu


1. Cc thuc tnh c bn ca MDH 1.1. Tnh c hiu p ng min dch c hiu c ngha l cc khng th hay cc t bo lympho T hiu qu ch c th gn vi khng nguyn hay chnh xc l cc quyt nh khng nguyn c tip xc trc . V d: nu ta tim chng phng bnh un vn th hot tnh min dch ch bo v cho c th chng li bnh un vn m thi. 1.2. Tnh phn bit cu trc bn thn v cu trc l Bnh thng h thng min dch khng to ra p ng min dch gy tn thng cho cc cu trc bn thn trong khi chng li c kh nng thi loi cc cu trc ngoi lai t c th khc (khng cng thuc tnh di truyn).

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1.3. Tr nh min dch

p ng min dch c to ra khi tip xc vi khng nguyn ln th nht khc vi p ng min dch khi tip xc vi chnh khng nguyn ln th hai c gi l p ng th pht : p ng min dch th pht xy ra nhanh hn, mnh hn v c th chuyn th ng bng cch truyn cc t bo lympho mn cm. 2. Cc yu t dch th tham gia p ng MDH Khng th l yu t dch th tham gia vo p ng min dch c hiu v c hai dng: - Dng lu hnh t do trong dch th c kh nng kt hp vi cc khng nguyn (QKN) ho tan c hiu dn n cc thay i sinh hc. - Dng biu l trn b mt cc t bo lympho B, c vai tr l th th khng nguyn ca t bo B cn c gi l cc globulin b mt (sIg). V bn cht, khng th l mt globulin v chng c nhng c im cu trc thc hin c chc nng min dch nn c gi l globulin min dch (immunoglobulin). Cn c vo s di chuyn trn in trng ngi ta cn gi chng vi tn chung l globulin gamma, tuy nhin thc t cn c cc lp di chuyn trn in trng thuc c khu vc globulin v . Cc globulin min dch c kh nng nhn dng rt nhiu quyt nh khng nguyn khc nhau. Khi kt hp vi khng nguyn c hiu, khng th c kh nng hot ha b th v khi b th c hot ha s dn n nhiu hot tnh sinh hc khc nh hin tng opsonin ha to iu kin d cho thc bo, ly gii t bo ch, trung ha cc c t ca vi khun, gy c t bo ph thuc khng th (ADCC). 3. Cc thnh phn t bo tham gia p ng MDH Cc t bo tham gia p ng min dch c hiu ch yu l cc t bo lympho c ngun gc t t bo mm trong ty xng, sau bit ha theo hai con ng khc nhau to nn hai qun th lympho c chc nng khc nhau: t bo lympho T v t bo lympho B. T bo lympho T bit ha tuyn c, chu trch nhim v p ng min dch qua trung gian t bo trong khi t bo lympho B bit ha trong ti Fabricius loi chim v trong ty xng cc ng vt cp cao khc, khi cc th th b mt t bo lympho B kt hp vi cc khng nguyn c hiu v cng vi cc tn hiu khc s lm cho t bo lympho B tng sinh ri bit ha thnh cc tng bo sn xut ra khng th c tnh c hiu tng ng. Ngoi ra thc hin c chc nng min dch c hiu cn c cc t bo khc cng tham gia vo nh t bo trnh din khng nguyn, dng bo, bch cu ht trung tnh..v..v.. 4. Cc phng thc p ng MDH C ch p ng min dch c hiu c th hin hoc bng cch to ra cc khng th hoc qua trung gian ca cc t bo lympho T hoc c hai. Phng thc p ng kiu no ty thuc bn cht v v tr xm nhp ca khng nguyn. 4.1. Min dch dch th Cc khng th c th bt ng cc vi sinh vt, ngn cn kh nng dnh ca vi sinh vt vi cc th th trn b mt ca t bo thc bo, trung ha c t, hot ha b th lm ly gii t bo ch, hin tng opsonin ha lm d cho s thc bo. Khng th c to ra bi cc tng bo do s bit ha v tng sinh dng t bo lympho B c kch thch bi cc khng nguyn. S tng tc gia khng nguyn v t bo lympho B c th xy ra bi hai c ch: ph thuc t bo lympho T hoc khng ph thuc t bo lympho T.

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Hnh 1.1. C ch hot ng ca globulin min dch i vi tc nhn gy bnh

4.1.1. p ng min dch dch th khng ph thuc t bo lympho T p ng ny c quyt nh bi cu trc ca khng nguyn, c bit l cc phn t c cu trc trng lp vi cc quyt nh khng nguyn lp li, v d nhim trng Streptococcus pneumoniae. Do tnh cht cu trc nh vy s lm cho cc t bo thc bo nhn din d dng cc quyt nh khng nguyn v to nn nhng lin kt cho, kch thch s hot ha t bo lympho B bit ha thnh tng bo sn xut khng th . Nh vy s hot ha t bo B lc khi u l khng ph thuc t bo lympho T, khng th to ra ch yu l IgM v khng c tr nh min dch v p ng min dch khng bn vng. 4.1.2. p ng min dch dch th ph thuc t bo lympho T p ng ny c vai tr rt ln trong min dch chng nhim trng c c t, v d bnh bch hu v un vn. Khi khng nguyn kt hp vi cc th th b mt t bo, s c nhp ni bo trong cc ti thc bo (phagosome). y khng nguyn s phn ct thnh cc peptid bi cc enzym t bo. Sau cc peptid s c vn chuyn n b mt t bo cng vi phn t ha hp m ch yu bc II, gi tt l MHC bc II. Phn t MHC trnh din peptid khng nguyn vi th th c hiu ca t bo lymphoTCD4+ (t boTh2) gi tt l TCR (T cell receptor).

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Hnh 1.2. Cc hnh thc p ng min dch dch th

4.2. p ng min dch qua trung gian t bo p ng min dch qua trung gian t bo c th thc hin qua hai c ch: (1) lin quan n t bo lympho TCD4+ ( t bo Th1 ) nhn din khng nguyn do phn t MHC bc II trnh din trn b mt cc i thc bo, (2) lin quan n t bo lympho TCD8+( t bo T c tay gi tt l t bo Tc), nhn din khng nguyn do phn t MHC bc I trnh din trn cc t bo c nhn . 4.2.1. Vi sinh vt gn ti thc bo (p ng ca t bo lympho TCD4+) Khi cc vi khun lao, vi khun hi xm nhp vo c th, vi sinh vt lp tc c thc bo. Trong t bo cc vi khun pht trin cc c ch ngn cn s ph hy ca i thc bo v d sn xut fibronectin, cc enzym kh con ng dit khun cn oxy, ngn cn ha mng vi cc th tiu bo. Cc vi khun nhn ln trong cc ti ni bo v sn xut cc peptid , cc peptid s c vn chuyn n mng v c phn t MHC bc II trnh din vi t bo Th1. T bo Th1 sn xut IL-2, IFN-, TNF (tumour necrosis factor) tc ng tr li i thc bo, ring IFN- v TNF- hip ng tc ng trn hai con ng dit khun ca i thc bo (ph thuc oxy v khng ph thuc oxy). TNF- c vai tr to u ht, yu t ha hng ng cc bch cu v bc l cc yu t dnh trn b mt cc t bo ni mc gip cc bch cu xuyn mach.

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Hnh 1.3. p ng min dch c hiu i vi mycobacterium

4.2.2. Khng nguyn vi sinh vt t do trong bo tng (p ng ca t bo TCD8+) Ph bin nht l cc khng nguyn vi rut, mc du mt s vi khun nh Listeria monocytogenes c th thot khi cc ti ni bo vo bo tng. Cc vi rut vo t bo bng cch gn vo cc th th c hiu, v d th th CD21 i vi virut Epstein- Barr, th th CD4 i vi phn t gp120 ca HIV,... V tr phn b cc th th l mt trong cc yu t quyt nh i tnh t chc ca vi sinh vt. V d : cc vi rut bnh di gn vi th th acetylcholin c cc tip hp thn kinh, do c kh nng truyn mm bnh n thn kinh trung ng. Mt khi vo t bo , cc virut sao chp v dch m, cc protein ca vi rut vo bo tng v vn chuyn n h li ni m th , sau chng c vn chuyn cng phn t MHC bc I n mng t bo trong nhng ci ti. Phc hp peptid KN-MHC c nhn din bi cc th th c hiu vi khng nguyn c trn t bo lympho TCD8+ (Tc), nhng t bo ny c kh nng tiu dit t bo ch bng cc enzym t t bo lympho Tc vo t bo ch v gy cht t bo (apoptosis). Ngoi ra cn c c ch th hai thng qua cc cytokin TNF-, IFN- do t bo lympho Tc tit ra s iu bin s tng hp protein t bo ch gy cht t bo.

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Hnh 1.4. p ng min dch c hiu i vi cc vi rt

IV. ng dng gy min dch phng nga nhim trng


Ngn nga bnh bng c ch min dch chng t s hiu bit v bnh nhim trng hoc kh nng min dch ca lch s loi ngi, v d dng vy u ma ngi nhm ngn nga bnh u ma c nhc n t 590 nm trc cng nguyn ti Trung Quc. Ngy ra i ca ngnh min dch hc nh du bi s thnh cng ca Edward Jenner trong chng nga u ma (1798) v gn mt th k sau, ngi ta hiu bit v vn chng nga nh nhng thnh cng ca L. Pasteur. Thi k ng ghi nh cho vic gy min dch ngi l nm 1885. Cu b Joseph Meister c tim vc xin chng bnh ch di ln u tin. 1. Min dch ch ng Min dch ch ng t cn bn trn c ch min dch tng ng vi s khng vi tc nhn vi sinh vt, c th thc hin c m khng c nguy c gy nhim trng cho vt ch. Mc p ng c c ph thuc vo min dch t nhin i vi bnh. V d cc khng th lu hnh trong mu trc tip i vi ph cu khun s ngn cn kh nng nhim bnh nng do chng lm cho vi khun nhy cm hn vi cc c ch thc bo. Kch thch p ng min dch c th thc hin vi polysacarid vch t bo vi khun m khng cn gy nhim vi ph cu khun thc s. Khi c gy mn cm vi khng nguyn, c th s khi ng mt lot p ng mc t bo v dch th, in hnh vi nhng tnh cht: c hiu, a dng, hiu ng phn t v c tr nh min dch

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2. Min dch th ng

Min dch th ng do s dng khng th c hiu. Thc t thng dng iu tr cc bnh gy ra bi c t nh un vn, khng th chng nc c ca rn. Min dch th ng thng ngn do khng th b ging ho trong khi p ng min dch ch ng khng c to ra, khng c tr nh min dch nn vt ch khng c bo v trong ln nhim sau. Min dch th ng xy ra thi k s sinh do khng th thuc lp IgG ca m truyn qua nhau thai cung cp tm thi kh nng bo v i vi nhim trng trong thi k u sau sinh. Mt khi khng th ca m ging ho th a tr s nhy cm nhim trng tr khi n pht trin c p ng min dch ch ng. Min dch th ng s dng globulin min dch ngi, huyt thanh ng vt hoc huyt tng v cc ch phm ca chng. Cn quan tm n cc phn ng phn v, bnh huyt thanh, nhim trng km theo nh nhim vi rut vim gan B..v..v.. 3. Nguyn tc khng nguyn ca mt s loi vc xin 3.1. Vc xin vi rut v vi khun bt hot hoc gim c lc Cc vc xin vi khun gim c lc nh lao, cc chng v hi Salmonnella typhi, Vibrio cholerae, Bordetella pertussis. Vc xin ny thng c hiu qu hn ch v thi gian min dch ngn. Cc vc xin vi rut gim c lc c v hiu qu hn, ngi ta chit xut vi rut gim hot t mi trng nui cy chuyn t bo nhiu ln nh bi lit, si, st vng. Cc vc xin vi rut bt hot nh cm, ch di v vim no Nht bn B. Cc vc xin vi rut thng cho p ng min dch c hiu lu di, c th cho tr c kh nng bo v sut i . 3.2. Vc xin tinh khit S dng khng nguyn tinh khit ngn nga bnh gy ra do c t vi khun. V d gii c t (toxoide) v hi m khng lm mt tnh khng nguyn, dng trong vacxin bch hu v un vn. S dng khng nguyn polysacarid ca ph cu khun, tuy nhin polysacarid khng kch thch to ra cc t bo c tr nh min dch. Vc xin vim gan vi rut B s dng cc peptid khng nguyn v bng phng php ti t hp gen bng cng ngh sinh hc. 3.3. Vc xin tng hp Da trn s tng hp nhng ng phn (polymer) chui thng hoc nhnh (3-10 axit amin) da trn cu trc bit ca khng nguyn vi sinh vt. Tuy nhin bn thn peptid tng hp thng sinh min dch yu do phi gn vi protein kch thch p ng min dch . 3.4. Vc xin vec t vi rut sng Ngi ta a gen m ho khng nguyn vi rut gy bnh vo c th vt ch thng qua mt vi rut khc lnh tnh. Nh vy vi rut c s dng nh ngun khng nguyn trong c nhn . Tim vc xin vi rut ny vo trong nhiu loi vt gy c p ng min dch dch th ln t bo i vi khng nguyn do gen l sn xut, tuy nhin cho n nay vn cha c th nghim ngi bi v s an ton nhng trin vng ca n th khng cn bn ci.

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10

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Chng 2

. 10

T CHC V T BO CA H MIN DCH


I. T chc lympho
T chc lympho gm c cc t bo lympho, t bo biu m v cc t bo m c phn b vo mt t chc c lp c nang bao bc hoc c phn b di dng mt t chc lympho lan ta khng c nang bao bc. Cc t chc lympho cha cc t bo lympho cc giai on pht trin khc nhau c phn loi thnh: - T chc lympho s cp (trung ng): gm tuyn c, ti Fabricius ( loi lng v) hoc ty xng ( ng vt c v). - T chc lympho th cp (ngoi vi): gm lch, hch bch huyt v t chc lympho lin kt vi nim mc. 1. T chc lympho s cp T chc lympho s cp l ni m qu trnh bit ha ca cc t bo lympho khng cn s kch thch ca khng nguyn. Tt c cc t bo ca h min dch u c sinh ra trong ty xng t cc t bo mm (stem cells). Mt qun th cc t bo mm tin thn ca t bo lympho T (pre-T cells) s ri ty theo ng mu n mt t chc c hai thy di c, l Tuyn c, ti y chng tip tc bit ha thnh cc t bo lympho T trng thnh (mature T cells). Mt qun th cc t bo mm khc tin thn ca t bo lympho B (pre-B cells) s i n ti Fabricius hay tip tc li ty xng bit ha thnh cc t bo lympho B trng thnh (mature B cells). Nh vy, tuyn c v ti Fabricius (hoc ty xng) l nhng t chc lympho s cp m cc t bo lympho n c tr u tin v khi ri khi ni y, chng thu c nhng yu t di truyn quan trng cho php chng nhn bit c cc khng nguyn t thn dung np v nhn bit cc khng nguyn l loi b. C th ni t chc lympho s cp nh mt loi trng hc dnh ring hun luyn cc t bo lympho. Chnh ti ty xng m cc t bo lympho B c c cc Ig (Immunoglobulin) u tin v cng chnh ti tuyn c m cc t bo lympho T c c cc cht tip nhn khng nguyn (T cell receptor,TCR) u tin xut hin trn mng t bo. 1.1. Tuyn c (Thymus) 1.1.1. Cu trc Trong qu trnh pht trin ca c th, tuyn c l t chc lympho c hnh thnh sm nht vo khong tun l th 6 ca thai k, t t l ln nht vo thi s sinh v bt u thoi trin vo tui dy th nhng khng bao gi bin mt hon ton. V cu trc th tuyn c ng vt c v l mt t chc lympho biu m, nm trong lng ngc pha trc tim v cc mch mu ln, phn lm 2 thy, mi thy li phn lm nhiu tiu thy ngn cch vi nhau bi mt b t chc lin kt.

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V phng din m hc, tuyn c c chia thnh 2 vng: vng v v vng ty. Cc t bo biu m ca tuyn ni vi nhau thnh mt mng li, tha tht vng v nhng li dy c vng ty m c l chng c chc nng trong qu trnh bit ha ca cc t bo lympho. Ngoi ra trn mng li t bo biu m cn c cc t bo dng bch tuc (interdigitating cells) mang nhiu phn t MHCII m ngi ta cho rng chng cn thit cho cc t bo lympho trong vic hc nhn bit khng nguyn t thn. Trong vng ty cng thy cc tiu th Hassal, chc nng cha c bit, c th l ni cha cc t bo biu m b thoi ha. Cc t bo lympho khi cha ri khi tuyn c th c gi chung l cc t bo tuyn c (thymocytes) c s phn b kh khc bit. vng v, cc t bo tuyn c phn b dy c vi rt nhiu hnh nh phn chia (c lng s phn chia cao gp 7 ln hn cc ni khc). vng ty, t bo tuyn c tha tht hn v c kch thc nh, y chnh l cc t bo lympho T trng thnh chun b ri tuyn c i vo tun hon n c tr ti cc t chc lympho th cp. 1.1.2. Chc nng Th nghim ca Miller ct b tuyn c chut nht s sinh nhn thy chut con c cc biu hin nh mt kh nng thi loi mnh ghp, gim r rt p ng min dch to khng th i vi mt s ln khng nguyn (khng nguyn ph thuc tuyn c), gim s lng t bo lympho T trong mu v trong cc t chc lympho th cp. Sau khi nui t 2 n 3 thng, chut khng ln, lng x, a chy ko di,... gi l mc bnh ci (wasting disease). Nh vy r rng tuyn c l trng hc o to v hun luyn cc t bo tuyn c non tr tr thnh cc t bo lympho T trng thnh m nhim nhiu chc nng chuyn bit, c bit l chng chu trch nhim trong p ng min dch qua trung gian t bo (cell mediated immunity) v iu ha p ng min dch. 1.2. Ti Fabricius (Bursa Fabricius) 1.2.1. Cu trc Ti Fabricius ch thy loi lng v, y cng l mt t chc dng lympho biu m c hnh thnh sm nhng cng thoi trin sm. Khi u, n l mt ci ti lng hp, thng vi nhp (cloaca), nim mc c v thanh mc tip lin vi cc thnh phn tng ng ca ng tiu ha nhng cc lin bo y khng c cc t bo tit nhy. Ti ny sinh ra cc chi l cc nang lympho biu m cng chia lm 2 vng: + Vng ty gm cc lin bo l cc t bo li, i thc bo v cc t bo lympho non ang phn chia. + Vng v, ngoi lin bo l cc t bo lympho B trng thnh v mt s tng bo (plasmocyte). ng vt c v, khng c ti Fabricius nhng thay vo l c nhng m t bo to mu trong gan phi hoc trong ty xng ca ng vt trng thnh, chnh cc t no ny s pht trin thnh cc t bo lympho B. Vy ty xng l t chc tng ng vi ti Fabricius v mt chc nng. 1.2.2. Chc nng Nu ct b ti Fabricius phi g trc ngy th 17 th thy: g khng c kh nng p ng to khng th, trong mu khng c cc globulin min dch, vng c tr dnh cho t bo lympho B trong cc t chc lympho th cp tha tht, khng c cc nang lympho v khng thy xut hin cc trung tm mm.

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Nh vy r rng ti Fabricius v ty xng l ni bit ha v trng thnh ca dng t bo lympho B l cc t bo c tim nng sinh khng th, chu trch nhim chnh trong p ng min dch dch th. 2. T chc lympho th cp Lch, hch bch huyt, t chc lympho nim mc,... cu thnh t chc lympho th cp. Ni sinh sng ca cc t bo lympho trng thnh n t cc t chc lympho s cp v l ni gp g vi cc i thc bo. Chnh trong nhng t chc lympho th cp ny m cc p ng min dch c thc hin. 2.1. Hch bch huyt Hch bch huyt ngi thng c hnh ht u, pha lm gi l rn hch ni cc mch mu n v i. Nu b dc mt hch bch huyt ta thy hch c bao bc bi mt bao collagen c cc nhnh n su vo nhu m hch v c th phn bit lm 3 vng: - Vng v: L vng t bo lympho B cn gi l vng khng ph thuc tuyn c. y cc t bo lympho b tr st nhau to ra cc nang lympho s cp. Khi c khng nguyn kch thch, cc nang s cp pht trin rng xut hin cc nang th cp. - Vng cn v: L vng t bo lympho T cn gi l vng ph thuc tuyn c. Nu mt ni no trn da b khng nguyn xm nhp th s c s tng sinh ca cc t bo lympho T ti vng cn v ny, ngc li khi ct b tuyn c hoc khi tuyn c b teo th vng cn v cha rt t t bo. - Vng ty: C nhiu xoang bch mch, t chc lin kt v mt t lympho xm nhp t vng cn v vo. Hch bch huyt l mt t chc lympho th cp, c trch nhim thanh lc khng nguyn khi chng xm nhp vo c th bng ng bch huyt (ch yu qua da). Do vy, hch thng nm ti ni phn nhnh ca cc b mch bch huyt. 2.2. Lch Lch khng ch l mt t chc lympho th cp m cn l c quan to mu trong thi k bo thai v c lc trng thnh mt s ng vt . Lch cng c bao bc bi mt bao collagen v khi ct dc thy 2 vng: - Vng ty : L ni ph hy cc hng cu gi - Vng ty trng: L ni tp trung cc t bo lympho gm 2 vng nh: + Vng tp trung t bo lympho T l vng chung quanh tiu ng mch lch, cn gi la vng ph thuc tuyn c ca lch. + Vng tp trung t bo lympho B to thnh cc nang lympho l vng cng trong ty trng nhng khng bao quanh ng mch, cn gi l vng khng ph thuc tuyn c ca lch. Khi c khng nguyn kch thch, cc nang lympho s cp s pht trin thnh cc nang th cp cha cc t bo lympho di dng hot ng tng t nh cc nang th cp trong hch bch huyt. Ngoi chc nng ca lch i vi h to mu, v phng din min dch hc c th xem lch nh mt mng lc ln x l cc khng nguyn xm nhp c th bng ng mu. 2.3. Cc t chc lympho lin kt vi nim mc (MALT)

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Cc t chc lympho th cp khng c nang bao bc cn gi l t chc lympho lin kt vi nim mc (MALT = Mucosa-associated lymphoid tissu) v n nm di vng nim mc ca nhiu c quan v t chc khc nhau. Mt trong nhng t chc lympho lin kt nim mc quan trng l hch hnh nhn nm quanh vng hu (gm tuyn hnh nhn khu ci, li, vm v hu) hnh thnh vng Waldeyer. y l ni cha nhiu t chc lympho di dng cc nang lympho th cp. ng tiu ha, t chc lympho lin kt nim mc chia lm 2 loi. loi tp trung v loi phn tn: + Cc mng Peyer l ni tp trung cc t bo lympho to thnh cc nang vi s lng t 200 n 300 mng, cc mng ny nm v pha b t do ca rut. + Cc t bo lympho loi phn tn th ri dc theo nim mc ng tiu ha k c rut tha. Dc theo nim mc ph qun v nim mc ng tit niu sinh dc cng c nhiu t chc lympho nim mc tng t. Thnh phn t bo t chc lympho nim mc gm c t bo lympho B v T nhng cc t bo lympho B sn xut khng th IgA tit l chim a s (IgA tit l mt khng th c kh nng i qua lp nim mc v gip nim mc chng vi s xm nhp ca cc vi sinh vt). Vy c th ni rng t chc lympho nim mc c vai tr rt quan trng trong cc p ng min dch ti ch.

S 2.1. Lin h gia t chc v t bo lympho

3. Lin h gia t bo v t chc lympho 3.1. S di chuyn ca t bo lympho Cc t bo non dng lympho xut pht t t bo mm ca ty xng s theo ng mu n t chc lympho s cp tng ng, ti y chng c hun luyn thnh cc t bo lympho B hoc T trng thnh nhng cha tip xc vi khng nguyn nn gi l cc t bo cn trinh (virgin cells). Cc t bo li c chuyn vn bng ng mu n cc t chc lympho th cp c hoc khng c nang bao bc m y chng c thi gian sng t vi tun cho n vi nm. Mi ngy c khong 109 t bo lympho ri khi cc t chc lympho s cp n t chc lympho th cp v s vo ng v tr nht nh dnh cho chng thc hin chc nng ca mnh khi c khng nguyn xm nhp. 3.2. S ti tun hon ca cc t bo lympho

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Cc t bo lympho sau khi n cc t chc lympho s cp khng c nh ti ch m lun lun c s ti tun hon. Mt s t bo sau khi n lch, bch huyt, t chc lympho nim mc,... thc hin chc nng ca n ri cht i. Mt s khc th li tip tc ra i bng ng bch huyt, tr li mu ri quay tr li hch hoc lch,... v c nh th to thnh mt nhm cc t bo tun hon nhiu nm trong c th. Mi gi c khong 1-2% tng lng t bo lympho lu thng trn cc con ng ni trn, s lu thng ny l cn thit gip cho t bo tr v ng ni c ng ca mnh v gip cho chng c iu kin tip xc vi cc khng nguyn xm nhp. V mi t bo lympho ch c hiu cho mt loi khng nguyn cho nn nu khng c s lu thng lin tc ny th cc lympho s kh tm gp c khng nguyn tng ng mt cch kp thi.

S 2.2. Nhim v ca cc t bo lympho trong t chc lympho

II. Cc t bo tham gia p ng min dch


1. Ngun gc

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Hnh 2.1. S bit ho cc dng t bo t t bo mm

Tt c cc t bo ca h min dch u pht xut t cc t bo mm vn nng ti ty xng. Cc t bo ny bit ha thnh 2 dng t bo chnh: - Dng lympho: Cc t bo mm chung ca dng lympho bit ha tip thnh cc t bo tin B hoc tin T, theo th t cc tin t bo ny s ri ty xng n t chc lympho s cp. Ngoi ra cn c mt qun th lympho th 3 gi l lympho nuls c nhng tnh cht rt khc vi 2 qun th lympho trn m ngun gc cha c xc nh mt cch r rng. - Dng ty: Cc t bo mm chung ca dng ty s bit ha tip thnh cc bch cu n nhn, cc bch cu ht v tiu cu ... 2. Cc t bo dng lympho 2.1. T bo lympho B 2.1.1. Bit ha Cc t bo mm dng lympho bit ha thnh cc t bo tin B khi u bng s tng hp chui nng (muy) trong bo tng nhng cha c chui nh. Tip theo l s tng hp chui nh m phn ln thuc typ (kapa), chui nng v chui nh ghp li thnh phn t Ig trong bo tng gi l CIg (cytoplasma immunoglobulin). Cc CIg ca t bo tin B sau c biu l ln b mt t bo gi l SIg (surface immunoglobulin). cc t bo lympho B trng thnh u c SIg thuc lp IgM hoc phi hp gia lp IgM v IgD.

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Hnh 2.2 S bit ho ca t bo lympho B

2.1.2. Du n Cc t bo lympho B chim khong 5-15% t bo lympho ca mu. Trong qu trnh bit ha, chng biu l mt s du n b mt (surface marker), du n c tnh cht kinh in l S Ig m a s l IgM n phn c u k nc ca chui nng gip cho vic neo phn t vo mng t bo. y l th th ch yu m t bo lympho B dng nhn bit khng nguyn. Ngoi ra cc t bo lympho B cn c cc du n khc nh MHCII, cc th th dnh cho b th (CR2, CD21), cng nh cc du n khc: CD19, CD20, CD22,... 2.1.3. Hot ha Khi mt khng nguyn i vo c th chng s chm trn vi mt lng khng l cc t bo lympho B c mang cc khng th b mt khc nhau. Mi mt khng th c v tr nhn bit khng nguyn v khng nguyn th ch kt hp vi khng th no ph hp vi n nht. Cc t bo lympho B khi kt hp c vi khng nguyn s nhn c mt tn hiu khi ng tip tc bit ha thnh tng bo, l cc t bo c tim nng sinh khng th. Do cc t bo lympho B c chng trnh ha ch sn xut mt loi khng th c hiu no m thi cho nn cc khng th va mi c tng hp bi tng bo s hon ton tng ng vi khng th gc ban u. Nh vy khng nguyn chn khng th nhn bit mnh mt cch c hiu qu. S hot ha t bo lympho B cn ph thuc vo bn cht ca khng nguyn: - Khng nguyn khng ph thuc tuyn c typ I nng cao c th hot ha trc tip mt t l ng k lympho B. - Khng nguyn khng ph thuc tuyn c typ II c cu trc lp li khng b ging ha c th to ra lin kt cho (cross linking) hot ha t bo lympho B. - Khng nguyn ph thuc tuyn c th s hot ha t bo lympho B cn thit phi c s hp tc ca t bo lympho T h tr (Th) thng qua cc cytokin.

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Hnh 2. 3. Hot ho theo c ch chn lc khng nguyn ca lympho B

2.2. T bo lympho T 2.2.1. Bit ha

Hnh 2.4. Bit ho ca t bo lympho T

2.2.2. Du n Cc t bo lympho T chim khong 65% t bo lympho ca mu. Cc t bo lympho T trng thnh u c kh nng nhn bit khng nguyn nh vo TCR (T cells receptor), ti th

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th nhn bit khng nguyn ny c s phi hp vi phn t CD3 cho php hot ha t bo sau khi nhn bit khng nguyn. Nhng qun th t bo lympho T khc nhau cng mang nhng du n c hiu ring. V d: t bo lympho Th c CD4, Tc c CD8,... Cn c vo nhng du n ny m ngi ta c th nhn din c chng nh cc khng th n clon tng ng . 2.2.3. Hot ha

Hnh 2.5 . Hot ho t bo lympho T

Nh vy, s hot ha t bo lympho T ngh (TG) cn hi 2 tn hiu: Tn hiu 1: Gm 1 phc hp bc 3 TCR+KN( x l) + MHC tng ng . Tn hiu 2 : L Interleukin 1 (IL1) do t bo trnh din khng nguyn tit ra. 2.3. T bo lympho nuls Ngoi cc t bo lympho ni trn, cn c mt s t bo lympho khc chim khong 1525% t bo lympho ca mu v c vai tr quan trng trong phn ng gy c t bo. 2.3.1.T bo NK v LAK: c kh nng git cht cc t bo ung th gi l cc t bo dit t nhin hay t bo NK (Natural killer cells); t bo dit hot ha bi lymphokin (LAK=Lymphokin activated killer cells). 2.3.2. T bo K: c kh nng git cc t bo c bao ph bi cc khng th gi l cc t bo dit (killer cells) hay t bo gy c qua trung gian khng th (ADCC: Antibody dependent cellular cytotoxic cells). T bo lympho nuls c vai tr ti quan trng trong vic bo v khng c hiu chng vi rut v chng cc t bo ung th m khng cn phi c cc th th nhn bit khng nguyn, cng khng b gii hn bi MHC nh cc t bo lympho Tc. 3. Cc t bo dng bch cu n nhn 3.1. Cc i thc bo ca h li ni m Cc tin t bo n nhn sinh ra cc t bo n nhn, t bo ny mn ng mu di tr n nhiu c quan v t chc khc nhau v ti , chng bit ha thnh cc i thc bo ca t chc ni chng c ng. Cc i thc bo ny hnh thnh nn mng li gi chung l h

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li ni m (RES = reticuloendothelial system) c tc dng bo v c th loi b cc khng nguyn khi chng xm nhp vo mu v t chc. Ty theo t chc c ng v ty theo tng giai on bit ha m cc i thc bo ny c nhng tn gi khc nhau.

S 2.3. Bit ha ca i thc bo

Ngoi chc nng thc bo, m bo v tiu ha cc vt l, cc i thc bo ny cn tit mt s cht nh: cc enzym tiu protein, cc sn phm tham gia vo s khng nh C2 , C3 , C4, C5, interferon, interleukin 1, ... 3.2. Cc i thc bo trnh din khng nguyn Ngoi chc nng bo v s cp trn, mt loi t bo thuc dng bch cu n nhn cn ng vai tr cha kha trong vic khi ng cc p ng min dch c hiu. C th, chng hp ph khng nguyn, ct khng nguyn thnh nhng mnh nh trong bo tng ri trnh din n ln mng t bo cng vi MHC cc t bo lympho bo nhn din v hot ha lm thnh pha m mn cho p ng min dch c hiu. Cc t bo trnh din khng nguyn thy nhiu da, hch bch huyt, lch v tuyn c. T bo c trng cho loi ny l cc t bo Langerhans da lm nhim v bt gi, x l khng nguyn ri di chuyn vo vng v ca hch lympho gn nht trnh din khng nguyn cho cc t bo lympho T ti . Cc t bo dng bch tuc (interdigitating cell) gp nhng nang th cp ca t bo lympho B trong hch v lch cng l cc t bo trnh din khng nguyn. Nhng t bo trn cng thy tp trung nhiu ti vng ty ca tuyn c v bn thn chng c mang rt nhiu khng nguyn t thn. 4. Cc t bo dng bch cu ht c sn xut trong ty xng di dng nguyn ty bo vi tc khong 8 triu t bo mi pht v c i sng ngn ngi ch 2-3 ngy, chim 60-70% tng s bch cu trong mu. 4.1. Cc bch cu ht trung tnh Chim trn 90% bch cu ht trong mu. Trn b mt ca n c cc th th dnh cho mnh FC ca IgG v th th dnh cho C3 , nh cc receptor ny m bch cu ht trung tnh ( v i thc bo) d bm bt gi cc vi khun c gn vi khng th v b th (hin tng opsonin ha) do kh nng thc bo ca chng c nng cao v c hiu qu hn. Di nh hng ca cc yu t ha hng ng (chemotaxis factor), bch cu ht trung tnh b thu ht n v lm nhim v tiu thc bo, gii phng men tiu protid ng thi tit cc yu t hp dn thm cc bch cu khc lm cho phn ng vim ti ch c tng cng. Do

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vy bch cu ht trung tnh c vai tr rt quan trng trong phn ng vim cp do vi khun gy ra. Ngoi ra, bch cu trung tnh cn hin din ti cc vim khng do vi khun m do cc phc hp min dch. Nhiu bnh l do phc hp min dch xy ra bi s t tp qu mc ca bch cu ht trung tnh. Bch cu ht trung tnh cng p ng vi cc lymphokin nh yu t c ch di tn bch cu (MIF: Migration inhibition factor), yu t c ch s bm dnh bch cu,...cc yu t ny do cc lympho bo tit ra mc ch km gi bch cu ti ch xy ra phn ng vim. 4.2. Bch cu ht i kim v t bo mast Bch cu ht i kim tun hon trong mu ngoi vi vi s lng rt nh di 0,2% cn t bo mast th ch thy trong cc t chc m khng thy trong mu ngoi vi. Hai loi t bo ny c im ging nhau l trn b mt ca chng u c th th dnh cho mnh Fc ca IgE v trong bo tng ca chng c nhiu ht cha cc cht hot mch nh: histamin, serotonin, cht phn ng chm trong phn v (SRS-A: Slow reactive substance of anaphylaxis),... Khi c d nguyn bm ln cc v tr kt hp khng nguyn ca IgE s kch thch gy hin tng v ht gii phng cc cht hot mch. Cc cht ny tc ng ln cc t bo c trn gy co tht v tc ng ln thnh mch mu lm tng tnh thm ... v l nguyn nhn ca cc tnh trng d ng, phn v. 4.3. Bch cu ht i toan Ch c rt t trong mu ngoi vi khong 2-5% v cng nh bch cu ht trung tnh chng c kh nng tiu thc bo v tiu dit vi sinh vt nhng chc nng chnh ca chng l tp trung ti ni xy ra phn ng d ng. Trong bo tng ca bch cu ht i toan c nhiu ht cha cc men v cc cht c tc dng trung ha bt cc sn phm c gii phng ra do hin tng v ht t bo mast v bch cu i kim. Nh vy, bch cu ht i toan c tc dng iu ha s hot ha ca t bo mast v bch cu i kim. 5. Tiu cu Ngoi vai tr quan trng trong phn ng cm mu, tiu cu cn tham gia vo p ng min dch nht l trong phn ng vim. Tiu cu c hnh thnh t cc tiu cu m trong ty xng v trn b mt c cc th th dnh cho Fc ca IgG v IgE, cc th th dnh cho b th. Khi lp t bo ni m ca mch mu no b tn thng hoc khi c yu t hot ha tiu cu (PAF= Platelet activating factor) th ngay lp tc tiu cu s tp trung n v ngng vn tiu cu ng thi gii phng cc yu t lm tng tnh thm thnh mch, hot ha b th thu ht bch cu n ni tn thng to phn ng chng hu hiu hn.

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