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  • 1. KHA C NH MI N D CH H C C A B NH NHA CHUMichael P. Mills, DMD, MS, Assoc.ProfThi gian: 4h. 8/10/2010M C TIU H C T P: nh ngha min dch t nhin v min dch thu c. M t cc thnh phn c bn ca min dch t nhin v min dch thuc. So snh 5 lp khng th. Gi c tn cc loi t bo bch cu chnh.Tm tt 4 loi phn ng qu mn i vi nhng cht ngoi lai. Tho lun ngun gc, s trng thnh v chc nng ca t bo T v B. Hiu c vai tr ca cc phc hp vi khun trong bnh nha chu. Tho lun vai tr ca qu trnh vim trong s ph hy m nha chu.N I DUNG: Cn bng ni mi v h min dch Cc thnh phn ca h min dch Ba c im quan trng ca min dch thch ng Cht gy p ng min dch v khng nguyn (KN) Nm lp [di lp] ca globulins min dch Bch cu mu Bch cu ht Monocytes - Macrophages Lymphocytes S trng thnh ca t bo T v B Cc loi phn ng qu mn Tin trin ca sang thng nha chu vim Sang thng ban u (2-4 ngy) Sang thng sm (4-7 ngy) Sang thng n nh (2-3 tun) Sang thng tin trin Osteoimmunology Tm li Ti liu tham kho Thng tin tc gi1

2. n nh n i mi v h mi n d ch: Bnh sinh bnh nha chu l mt ch phc tp, i h i mt s hiu bit t m v cc c im i th v vi th ca m nha chu (l cutrc nng rng), cng nh vai tr ca h th ng min d ch trong png ca k ch.C th con ngi lun hot ng lin tc gi mi trng bn trongc th trong trng thi n nh ni mi (homeostasis). H thng gipphng bnh v cung cp sc khng (resistance) i vi cc VSV ngo ilai l h thng min dch. Trong xoang ming, VSV trong mng bm b tu lm tn thng nu bng cch kch hot mt phn ng vim tich. H thng min dch ca k ch to ra qu trnh vim b o vnhng khng may l n gp phn vo s ph hy m trong b nh nhachu.C nhiu tin b trong nhiu thp nin qua trong vic lm sng tbn cht phc tp ca h min dch. Kh nng bo v ca h min dchph thuc vo kh nng cc t bo min dch (immune cells) lin h vinhau c hot ng phi hp. Cc t bo c kh nng truyn hay g icc tn hiu (signals) cho nhau thng qua s tip xc t bo-t bo haybng cch tit ra cc cytokines. Cc t bo phn ng vi nhau hay v i 2 3. cytokines thng qua cc receptors v ligands gn trn mng t bo.Ligands l cc phn t gn vi cc receptors lm kh i u m t tn hi u.Tht vy, hng trm receptors v ligands c xc nh b i cc nhmin dch hc trn ton Th Gii. Ngy nay, mi receptor c nhcn bng cch s dng mt thut ng quc t gi l cm bit ha("Cluster of Differentiation") hay CD. Sau CD l mt con s ch th tm receptor c pht hin. V d, tt c lymphocytes T u creceptor CD3. Tuy nhin, mt loi c bit ca lymphocyte T c gi lt bo T gip ("Helper" T Cell) cn c receptor CD4.Cc thnh ph n cha kha c a h mi n d ch ng vt bc cao, s khng chng li tc nhn gy bnh baogm mt p ng bm sinh, khng c hiu (MD t nhin) v m t png c hiu (MD thu c hay MD mc phi), chng ho t ng ph ihp bo v k ch. p ng MD bm sinh xy ra theo cng mt cchv cng mc bt k gp tc nhn gy bnh bao nhiu ln. Ngc li,p ng min dch thu c xy ra sau khi mt tc nhn gy bnh ti pxc vi k ch v pht sinh mt "p ng c hiu" vi tc nhn gybnh v c lu tr trong mt ngn hng b nh (memory bank)cho bt k ln tip xc no sau ny. ln tip xc th 2 v i tc nhngy bnh, mt p ng min dch nhanh hn v mnh hn s xy ra loi b tc nhn .Min dch t nhin hay MD bm sinh (Innate immunity) bao gm: Hng ro da, nim mc, cc dch tit ca c th v thm ch l cc VSVthng tr (ni sinh). Cc yu t sinh l nh pH v nhit c th. Bch cu trong mu v m (neutrophils, monocytes, macrophages,mast cells, basophils, eosinophils v t bo dit t nhin NK (naturalkiller cells)). T bo ui gai (Dendritic cells) chu trch nhim gim st mi n d ch(immune surveillance) v trnh din KN. M lymph trung ng v ngoi bin. Cc cht trung gian ca qu trnh vim gm protein phn ng pha cp(acute phase proteins), b th (complement) v cytokines.Min dch thu c hay mc phi (adaptive or acquired immunity) thqua trung gian t bo T v t bo B. C 3 c im quan tr ng c a MDthu c: Nhn din khng nguyn Tnh c hiu Tr nh min dch3 c i m quan tr ng c a mi n d ch thu c (MD thch ng): 3 4. Nh n di n khng nguyn (Recognition) ngi khe mnh, p ng MD khng c sinh ra chng li ccthnh phn ca chnh c th. ng vt c xng sng, phc hp ha hp m ch yu (MHC- MajorHistocompatibility Complexes) tn ti cho php phn bit gia KN cabn thn (self antigens) v KN khng ca bn thn (non-self antigens). ngi n c gi l KN bch cu ngi (HLA- Human LeukocyteAntigen) chu trch nhim m ha v mt di truyn cc t bo c angi c h thng min dch nhn din. Cc t bo c nhn ccc gen MHC lp I, trong khi cc t bo trnh din KN (antigen presentingcells -APCs) - mt di nhm ca t bo MD- c cc gen MHC l p II. mt t bo khe mnh, phn t MHC lp I kt hp vi mt trong nhngpeptide t bo c biu hin trn b mt t bo. Phc h p ny ho tng nh mt tn hiu lymphocytes dit t nhin (t bo NK) hay tbo Tc c t bo (cytotoxic T cells) khng tn cng. Tuy nhin, n u t bo b tc nhn gy bnh xm nhp, phn t MHC l p I s k t h pvi mt peptide ca tc nhn gy bnh (khng ph i c a b n thn) sau bo hiu cho lymphocytes tn cng v ph hy t bo. Cc t bo tri qua bin i c tnh cng c peptides v i phn t MHC l p Ikhng cn c nhn ra l ca bn thn na; do thc y s phhy cc t bo ung th.Tnh c hi u (Specificity)Tnh cht ny ni n kh nng ca h min dch nhn din cc KNkhng phi ca bn thn v p ng mt cch c hiu vi chng, ch khng phi l p ng ngu nhin, thng thng. Tnh c hiu ca MDthu c c m u bi cc t bo trnh din KN nh t bo T hot ha, t bo B, i thc bo, t bo ui gai (dendritic cells) v t bo biu m tuyn c. T bo APCs c phn t MHC lp II trn b m tc kt hp vi peptides KN. Khi peptide KN ny c trnh din chot bo T, t bo T s c hot ha v gip kch thch t bo B tngsinh v bit ha thnh tng bo (Plasma Cells) sinh ra khng th (antibodies) "c hiu" ch vi KN .4 5. Tr nh (Memory)S tip xc u tin vi mt phn t (KN) lm pht sinh p ng MD li mt du n thng tin. Vi s gip ca t bo T hot ha, t bo Bcng sinh ra cc t bo tr nh (memory cells) vi cc KT c hi u KNnm trn b mt ca chng nh l th th ca t bo B (BCR- B cellReceptors). Cc t bo tr nh ny sng trong thi gian di h n v khitip xc vi KN ln 2, c th cho p ng mnh hn v nhanh hn loi tr KN. Him khi chng ta mc bnh si, quai b,.. ln th 2. S tipxc ln th nht c ghi nh c th y li s xm nh p l nk tip. Vaccines l dng tng hp hoc l KN c x l kchthch sn xut KT. Mi ln KN xm nhp c th, c th ghi nh v m tp ng c hiu, thch hp c to ra bi KT v cc t bo MD ca kch.Ch t gy p ng mi n d ch (Immunogens) v khng nguyn(Antigens)Cht l (Foreign material), bao gm c VSV, c th c cha cc nhmha hc m c th nhn din l vt l. Cc phn t cc bt k nhm hahc no lm pht sinh p ng MD th c gi chung l ch t gy png MD (immunogens). c bit hn, mt phn t c kh nng lm sinh5 6. ra (generating) khng th (antibody) th c gi l khng nguyn(antigen). Nu mt VSV thot khi cc c ch phng v khc ca c th,h MD s to ra mt p ng c hiu trc tip ch ng li KN c a VSV.ImmunoglobulinsGlobulins min dch (Ig) l gamma globulin (protein) trong cc d ch c th (nh huyt thanh) v dch tit nim mc (nc bt, nc mt,dch m o), v cng tm thy vng m vim. Chng c sn xu tt tng bo, c bit ha t t bo B. Da vo cu trc v thnhphn protein, immunoglobulins c chia thnh 5 lp (class), 2 trongchng c chia nh hn thnh di lp (subclass). Mi Ig c c u trcha hc ring v chc nng sinh hc c trng.C u trc Ig i n hnhPhn t Ig gm vng hng nh (Constant region) v vng thay i(Variable region).Vng hng nh thng l c nht cho lp hoc di lp Ig v cho nhot tnh sinh hc. Vng thay i to ra hnh dng phc tp cho s bmdnh ca mi KN c hiu.5 l p [d i l p] Immunoglobulins Immunoglobulin G (IgG) [di lp IgG1, IgG2, IgG3, IgG4] Immunoglobulin A (IgA) [di lp IgA1, IgA2]6 7. Immunoglobulin M (IgM) Immunoglobulin D (IgD) Immunoglobulin E (IgE)IgGHin din ch yu trong mu v chim 70%-75% lng Ig trong mu.Nhiu di nhm IgG qua c hng ro nhau thai v ch u trch nhi mchng li nhim trng trong vi thng u ca i sng a tr. 7 8. IgACung cp s bo v ti ch trn cc b mt nim mc. N c tmthy trong cc dch tit nim mc nh nc bt, nc mt, m hi, dchmi, cc dch ca phi v sa non, dch ng tit niu-sinh d c vng tiu ha. L s phng v ch yu chng li VSV tn cng b m tnim mc. IgA c chc nng chng VSV bm dnh v xm nh p l p ph biu m nim mc.IgMIg ch yu hin din trn b mt ca t bo B tr ng thnh v c tcdng chng li VSV bng cch gn kt vi b th, gy ngng k t(agglutination) v ly gii VK (bacteriolysis). N l KT u tin tham giavo p ng MD v gi mt vai tr quan trng trong kim sot VK i votrong dng mu (nhim trng huyt). 8 9. IgDL KT chim lng rt nh trong huyt thanh v hin di n trn b m tca t bo B. N c lin quan n vic kch thch v c ch cc t bony trong sn xut KT.IgENng rt thp trong huyt thanh, tng trong phn ng d ng v m ts trng hp nhim k sinh trng.9 10. IgE gn kt vi i lc cao vi receptors trn mng (FceRI) c a t boMast trong m v basophils trong mu. Lin kt cho ca t bo gnkt vi IgE vi mt tc nhn gy d ng lm tit ra cc ha ch t trunggian vim nh histamine v nhiu cytokines. IgE cng l Ig chnh p ngvi nhim mt s k sinh trng. Khi VSV xm nhp c th, p ng u tin ca c th c thchin bi cc bch cu.B ch c u (Leukocytes) trong muc phn loi thnh 5 loi chnh da vo hnh thi v chc nng.Chng cng c phn loi thnh BC ht v BC khng c ht.BC chng li cc VSV xm nhp bng cch kch thch cc p ng MDdch th v MD t bo c hiu hay bng cch thc bo (phagocytosis).3 lo i BC h t (granulocytes):1. Neutrophils hay BC a nhn trung tnh (PMNs)2. Eosinophils3. BasophilsTn ca chng c t theo s bt mu ca cc ht trong bo tng. 10 11. Monocytes, loi BC th 4, c mt t ht v nhn hnh qu th n i nhnh. Trong m, monocytes tr thnh i thc bo (macrophages).Loi cui cng l lymphocytes. Chng l t bo trn khng c h t, nhnto cn xng vi t bo. Lymphocytes chu trch nhim ch y u cho MDthu c.B ch c u h tNeutrophils (PMNs) thng l t bo u tin di chuyn n v tr VSVxm nhp hay v tr chn thng. S di chuyn c hng ny (hahng ng-chemotaxis) c gy ra bi s tit cc phn t tn hiu(signaling molecules) c gi l chemokines c th c phng thchbi nhiu loi t bo khc nhau ti v tr vim. PMNs lo i b VSV xmnhp bng cch thc bo v cc c ch khc. PMNs chim 50-70% BCtrong mu v > 90% BC ht trong mu.PMN c 3 lo i h t:1. Ht th 1 hay ht a azua (azurophilic granules) l lysosomes ch aenzymes tiu ha mnh gm hydrolases, elastase, myeloperoxidase vproteins khc nh lysozyme v defensins.2. Ht th 2 hay ht c hiu (specific granules) ch a lactoferrin,lysozyme, collagenase v proteins khc.3. Ht th 3 cha gelatinase v enzymes khc.11 12. Eosinophils c lin quan trong s phng v chng li nhim k sinhtrng v trong kim sot phn ng d ng (qu mn). Eosinophils chi m1%-3% BC mu.Basophils chim