- Xam nhap qua ducmg bao thai: hien nay, ngudi ta da chumg minh duoc rang, nhi£u vat ky sinh cd kha nang cam nhiem qua dudng bao thai Fromann (1963) da xac dinh
1. mi £n dich ch6 ng kv sinh trung
Nhung benh ky sinh trung ra't pho bien, da va dang gay ra nhidu tu vong hon bat cu tinh trang nhidm trung nao khac, dac biet d cac vung nhiet ddi va cac nude dang phat tridn (Vu Trieu An va Jean Claude Homberg, 1997). Chi rieng doi voi benh sot ret, theo WHO (1992), tren thd gidi co khoang 120 trieu ngudi bi sot ret va 1 - 2 trieu tir vong m6i nam. Viet Nam la nude khi hau nhiet ddi, ngudi va dong vat luon nhidm ky sinh trung vdi sd lupng chung loai nhieu va cudng do nhidm cao (D6 Duong Thai va Trinh Van Thinh, 1978). Co the ngudi va dong vat dap ung nhu the nao? Dd la cau hoi ma ra't
nhieu ngudi quan tam tim cach tra ldi, hy vong tim ra dupe nhung phuong an phong nhidm ky sinh trung mot each huu hieu.
Noi mot each tong quat thi co the co dap ung midn dich vdi ky sinh triing nhung khong co may hieu qua, nen cac the nhidm ky sinh triing thudng mang tmh kinh didn, phan anh cuoc dau tranh lien tuc xay ra va da gay ra nhirng ton thuong keo dai, anh hudng den sue de khang cua co the vat chu.
1.1. Dap ung midn djch tu nhien
La dap ung ft hieu qua ddi vdi cac loai ky sinh triing da bao hay don bao. Mot so ldn ky sinh triing vuot qua hang rao phong ngu cua co the nhu da, niem mac nho cac vat chu trung gian (mu6i: truyen ky sinh triing sot ret, giun chi cho ngudi; ve: truydn don bao
Piroplasma cho bo, trau....) hoac vat moi gidi (ruoi trau va mong: truyen tidn mao trimg
Trypanosoma cho trau, bo, ngua...), hay nho kha nang cua chfnh ban than ky sinh triing (au triing giun dua co vo day da giup chung thoat dupe qua trinh thuc bao cua vat chu). Vi vay, su chong dd ciia co thd chii yeu dua vao dap ung midn dich dac hieu.
1.2. Dap ung mien djch dac hieu
Do ky sinh triing la mot sinh vat tuong ddi ldn nen co rat nhieu loai khang nguven khac nhau va m6i vat chii lai co mot cach dap ung rieng ciia minh.
1.2.1. Dap ung mien dich dich the
Vai tro ciia khang the dich the thay ro hon ddi vdi ky sinh triing don bao sdng ngoai te bao hoac khi ky sinh triing chua xam nhap vao trong te bao. Khang thd dich the co kha nang trung hoa ky sinh triing va tao thuan loi cho qua trinh thuc bao ky sinh trims.
6 nhung co the nhiem ky sinh triing. kha nang san xuat khang the dich the tang, nhung thudng ky sinh triing co rat nhieu vung man cam vdi khang thd (epitope khang
nguyen), vi vay tang san xuat khang the dich thd la mot phan ung da dong (da cion), trong do ngoai sir tang IgG, IgM thi sir tang IgE la kha dac hieu doi voi co the nhidm ky sinh trung. San xua't khang thd IgE dac hieu va tang bach cau toan tmh la bieu hien thudng thay trong co the gay nhidm ky sinh trung thuc nghiem hay trong benh ky sinh trung. d chuot, khi gay nhidm thuc nghiem vai san mang (Schistosoma) thi tha'y co tang bach cau toan tinh va nong do IgE trong mau. C) ngudi cung vay. Do la 2 chi tieu ca ban giup chan doan nhidm ky sinh trung.
Binh thudng d Viet Nam, nhung didu tra ban dau cho thay co tren 80% ngudi Viet Nam bi nhidm 1 - 2 loai ky sinh triing dudng ruot trd ldn. Vi thd ma d ngudi Viet Nam, tam goi la "ngudi binh thudng", ty le bach cau toan tinh chiem tdi 6% trong cong thuc bach cau va IgE ldn tdi 400 ng/ml, cao han ngudi d Chau Au va Chau My 2 - 3 lan. Co
che' cua dap ting nay la do khang nguydn ky sinh triing co xu hudng kich thich nhom te bao lympho T CD4+ tiet IL-4 va IL-5 (la nhung Cytokin do bach cau tiet ra) thuc te bao lympho B chuyen sang san xua't IgE va tuy xuong tang san xuat bach cau toan tinh.
Trong thuc nghiem, ngudi ta da tha'y duoc su phdi hap tac dung cua IgE vdi bach cau toan tinh theo co che doc te bao phu thuoc khang the ADCC (Antibody Dependent Cell - Mediated Cytotoxicity).
Trong dieu kien invitro, khi ngudi ta cho au trung Schistosoma vao ciing vdi bach cau toan tfnh va IgE (bach cau toan tfnh va IgE deu lay tir chuot da nhidm ky sinh triing nay) thi thay IgE bam vao a'u triing, dong thdi bach cau toan tinh sap tdi, vd hat va a'u
triing ky sinh triing bi tieu huy. Trong cac hat bach cau toan tinh co chua MBP (Major Basic Protein = Protein kiem chii yeu), tac dung ciia MBP con manh hon ca nhung men tidu protein hay cac goc tu do co trong thuc bao.
B ang 1. S u th a y doi mot so chi tieu mien dich if ngu&i bi sot ret ac tinh
(Dan theo Vu Trieu An va Jean Claude Homberg, 1997)
Chi so Ngi/di binh thuting Ngirdi sot ret ac tinh
IgG (Ul/ml) 178 198
IgM (Ul/ml) 128 191
Bo the (CH50) 32 13
Bach cau toan tinh/ml 365 21
Histamin (%) 11 75
Hoa hong E (Lympho T) % 62 44
Hoa hong EAC (Lympho B) % 29 32
P hut hop mien dich + 0 13
Trong bang tren. bach cau toan tinh giam trong can sot ret ac tfnh la do chung da bi mat hat nen khong phan biet duac r5 vdi loai bach cau trung tinh. Nhung dai thuc bao khi duac hoat hoa cung co kha nang nuot va tieu au trung thong qua cac goc tu do NO va TNF. Ngoai ra. cung phai ke den cac Ig khac nhu IgG2 hoat hoa bo the co the giup gay dung giai ky sinh triing.
Trong co the; ngucri bi sdt ret, khang thd dich th^ tang kha ro, nhung theo Cohen thi chi co mdt phan nho khoang 5% la co tac dung thuc su vdi ky sinh trung sdl r6t (Plasmodium), phan ldn con lai la nhirng khang thd tap khac. Nhung ro rang la trong con sdt ret ac tmh, nhung thay doi ve mot so chi tieu mien dich da cho thay la cd d ip ung nay.
Bang trdn cung cho thay, trong benh sdt ret co su giam dap ung qua trung gian \€
bao nhung co tang dap ung midn dich dich the, mac du mpt phan da tham gia vao su hinh thanh phuc hop midn dich. Cung vi the ma co su tidu thu manh bo the.
Mdt sd ky sinh trimg gay ra phan ung hat va phat trien xo. Trudng hop nay hay gap d au trung Cysticercus cellulosae cua san day Taenia solium. San day trudng thanh ky sinh d rudt non ngudi thai ddt san gia theo phan ngudi ra ngoai. Lon nudt phai ddt hoac trung san, au trung nd ra se qua niem mac da day, ruot vao mau, den cac co quan phat tridn thanh nang tai co van. Tai day, phan urng midn dich gay viem, tao thanh t6 chuc hat vdi mo xo phat trien xung quanh. Ngoai sinh thiet thi cd the ch^n doan bang ky thuat midn dich nhu: phan ung midn dich huynh quang, midn dich men ELISA. Vdi amip cung vay, nhat la khi chung gay ap xe gan, mot bien phap giup cho chan doan phan bidt la phat hien khang thd dac hieu chong khang nguydn amip. Trudng hcrp nhidm giun chi, co che cua hien tuong chan voi la do ky sinh trung phat trien trong mach bach huyet, tao ra t6 chuc xo lam tac nhung mach tuong ung thuoc dia phan co hien tupng phu.
1.2.2. Dap itng mien dich qua trung gian te bao (C M I: C ell M ediated lmmunoresponse)
Ngudi ta cho rang, midn dich qua trung gian te" bao la co che' phong thu quan trong
* JL/ —
nhat trong benh Leishmaniasis va Toxoplasmosis. 0 nhung con vat bj nhidm
Toxoplasma, cac td bao dai thuc bao da dupe hoat hoa dong vai tro quan trong trong dap ung midn dich.
Trong co the nhidm ky sinh trung cung san sinh ra nhung te bao doc TC (hay CTL), nhung chung co it tac dung va con phu thuoc nhieu vao co dia. Trong thuc nghiem gay nhidm chuot vdi Plasmodium bergei va dung chat chiet bach cau thi co the truydn phan nao sure de khang midn dich te bao cho chuot. Gay nhidm vdi don bao Leishmama tha'y co dong nhay va dong khang. 6 dong khang co su tang tiet IFN va TNF nhieu hon bdi cac td bao TCD4, nhung neu tiem khang the chong cac cytokin trdn thi tao ra con nhidm bot phai nhu d dong nhay. Ngupc lai, d dong nhay trong con nhidm bot phat thay tang
IL-4, nhung neu tiem khang the chong IL-4 thi lai co phan ung nhu dong khang. Ngudi ta cho rang, cac cytokin (IFN va TNF) lam tang hoat dong dap ung midn dich qua trung gian te bao, d day co su tham gia cua cac te bao h6 tro Thi, Th2 va cac dai thpc bao. con IL-4 co tac dung nhieu trong mien dich dich the nhung lai uc che dap ung mien dich qua trung gian te bao. Den nay, ngudi ta cung da thay bach cau toan tinh va tieu cau cung diet dupe ky sinh trung thong qua cac receptor be mat. Bach cau toan tfnh duoc tang sinh dudi tac dung cua interleukin 5 va dupe hoat hoa bdi interferon. Khi co I2A. IgE dac hieu tuong ung ket hop tren be mat ky sinh trung thi chung de dang bi tieu diet bdi bach cau toan tinh va tieu cau (thav doi vdi giun xoan. san mang va tien mao trung).
1.2.3. S u ne tranh dap ting mien dich cua ky sinh trung
Ky sinh trung co nhieu bien phap de lan tranh dap urng miSn dich cua co the: vat chu. Nhung bien phap thucmg tha'y la:
- Ky sinh trung luon luon thay doi cac khang nguyen be mat trong sudt chu trinh song cua chung. Co hai hinh thuc thay doi:
Mot la, thay doi qua tung giai doan. Hinh thuc nay thay dien hinh d kv sinh trung sdt ret (khi la the! liet, khi la thoa trung, khi la tieu th6 hoa cue). C) moi th6 nay, ky sinh trung sdt ret lai co nhung epitope khang nguyen rieng. Vi vay, khi co the ky chu vira tao ra duac khang the chong lai khang nguyen d the nay thi ky sinh trung da chuyen sang giai doan khac va ne tranh duac su de doa cua dap ung miSn dich.
Hai la, thay doi lien tuc khang nguyen be mat. Vf du dien hinh cua hinh thuc nay la tien mao trung Trypanosoma - loai ky sinh trung dudng mau co kha nang thay doi lien tuc khang nguyen be mat. M6i dot sd luong ky sinh trung trong mau tang len la mot lan chung thay doi tmh khang nguyen. Sd di Trypanosoma co kha nang nay la do chung co mot glycoprotein be mat thay doi - VSG (Variable Surface Glycoproteine). M6i
Trypanosoma co tdi tren 1.000 gen VSG khac nhau, m6i lan mot gen nay duoc sao ra va bieu lo, thay cho gen cu bi loai di. Cac loai tien mao trung khac nhau deu co cac Immunoglobulin cua vat chu gan vdi bS mat te bao cua chung. Ngudi ta cho rang, cac khang the nay khong gdn vdi tien mao trung qua vung bien d6i cua chung ma lai qua phan Fc cua phan tu khang the. Cac khang the nay co the che khuat ky sinh trung do va lam cho cac te bao co tham quyen midn dich khong nhan biet duac ky sinh trung.
Su thay doi tfnh khang nguyen nay lam kho khan cho viec che tao ra mot loai vac xin huu hieu ddi vdi ky sinh trung. Rieng ddi vdi ky sinh trung sdt ret, ngudi ta da phan lap duac mot khang nguyen CS (Circumsporozoit) khong thay doi va tu do tao ra duoc mot loai vac xin co nhiSu hua hen.
- Mot sd ky sinh trung nau minh ben trong te bao (vf du: Toxoplasma,
Plasmodium....) hoac trong mot vo boc day (vf du: amip, giun bao, giun ket hat....) nen moi kha nang mi6n dich cua ky chu khong tan cong duac. Khong nhung the, doi khi vo boc nay con co tac dung trung hoa lam bo the cung khong hoat dong duac, hoac lau lau vo boc lai tu bong ra va thay bang vo mdi.
Ngudi ta gia dinh rang, trong mot sd trudng hap, phuc hap khang nguyen - khang the trong huyet thanh cua vat chu gan vao be mat cua ky sinh trung, phong be mot cach co hoc cac tac dong cua khang the hoac lam ba cau, gay doc cho te bao va true tiep uc che tac dong cua cac lam ba cau. Co che trdn thoat miSn dich kieu nay la ca che cua cac giun, san ky sinh.
Su an nau cua ky sinh trung trong te bao co the- bao ve cho ky sinh trung tranh khoi cac tac dong co hai, hoac tac dung gay chet cua khang the, hoac ca che de khang cua te bao. Vf du: ky sinh trung sdt ret (Plasmodium) luc dau phat trien trong te bao gan, sau do trong hong cau. Chiing chi chiu lac dong cua khang the trong pha ngoai bao ngan ngui (giai doan Sporozoit va Merozoit). Khi ky sinh trong hong cau, Plasmodium tranh
dirpc ca che phong ho mien dich cua vat chu nhung cung tao ndn nhirng ba't lcfi cho ky sinh trung (chung phai lay dinh dudng qua ldp mang te bao cua vat chu va mang t<* bao cua chfnh no). VI vay, chung da lam thay doi cau true td bao cua vat chu bang cach c£c protein ciia chung gan vao mang hong cau, vi the chung tranh duoc dap (mg midn dich cua vat chii.
- Ddi vdi cac loai giun san kfch thudc tuong ddi ldn thi cho cu tru lau dai la long ruot, chung chi bi tieu diet khi vat chii duac sir dung thudc diet giun, san. Tuy nhidn, chung thudng phai trai qua thdi ky au triing. Vdi kfch thudc nho be, au triing phai di chuyen qua mau, gan hay phoi, khi a'y midn dich co kha nang phat huy tac dung, ndu khong tidu diet duac thi cung gay kho khan cho su phat trien ciia chung.
Mot sd loai giun san con l<£n tranh midn dich bang cach nau minh sau cac khang nguyen ciia chfnh vat chii, vi the ma ca the vat chii khong coi ky sinh trimg la vat la. Mot vf du ro nhat la a'u triing san mang Schistosoma: khi di chuyen tir da den ph6i, ngudi ta tha'y chung khoac la'y cac glycolipit ABO hay phan tir MHC II ciia vat chii (Major Histocompatibility Complex - cac phan tir MHC ldp II tha'y d cac te bao trinh dien khang nguyen nhu dai thuc bao, te bao lympho B....) nen phan ldn tranh dupe cac don midn dich ciia vat chii.
- Ky sinh triing con gay suy giam dap ung midn dich cua vat chii bang ban than cac chat doc ma chiing tiet ra. Ngoai ra, viec ky sinh trimg chiem doat dinh dudng cua vat chii, dan den tinh trang suy dinh dudng cung la mot cach gian tiep lam suy giam dap ung midn dich ciia vat chu.