KHNG NGUYN, KHNG TH V CC HP CHT SINH HC(ANTIGEN, ANTIBODY AND CYTOKIN)TS. HIU LIM*CHNG V

*5.1. ANTIGEN5.1.1. i cng5.1.2. Tnh cht5.1.3. Phn loi5.2. ANTIBODY-IMMUNOGLOBULIN5.2.1. i cng5.2.2. Cu trc phn t5.2.3. Cc lp globulin min dch5.2.4. Sinh tng hp khng th5.2.5. Tc ng sinh hc ca khng th5.3. CC HP CHT SINH HC5.3.1. B th5.3.2. Phc hp ha hp m chnh (MHC)5.3.3.Cytokine

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S P NG MIN DCH (IMMUNE RESPONSE)*

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5.1.1. I CNG Antigen (cht sinh bnh pathogen) c ngun gc t nm mc, vi khun, virus hay cc loi protein ngoi lai c kh nng sinh bnh (gy bnh) cho vt ch. Antigen hon chnh c 2 thuc tnh: tnh sinh min dch, tnh c hiu. Hapten (semiantigen) l hp cht hu c khng c tnh sinh min dch, nu c gn vi protein ti s to thnh antigen hon chnh.*

HaptenMW (daltons)Aspirin180Methyl DOPA211Penicillin320Gentamycin700

5.1.2. TNH CHT CA ANTIGEN(1).Tnh sinh min dch Trng lng phn t (polypeptide-10.000 dal, polysaccharide-100.000) Nhm quyt nh antigen (antigenic determinant) vi amino acid vng (Tyr, Trp, His...) Yu t c a ca vt chAntigen (vaccin) ph thuc Tnh l hay quen ca antigen Tnh d hay kh phn hy ca antigen Tnh d hay kh bt gi bi monocyte, macrophage Thnh phn t dc trong vaccin(2). Tnh c hiu antigen Tnh c hiu ca antigen Cc domain cu trc-nhm quyt nh antigen = Trung tm hot ng ca enzyme*

Nhm quyt nh antigen-Epitop-Nhn din khng th tng ng-Lin kt vi th th ca lymphocyte T hoc khng th(3). Epitop- Kch thc 1-3nm, MW=5 Kdal- Cu to 6-8 cu t amino acid hoc 4-6 phn t monosaccharide- S lng epitop l ho tr ca antigen *

antigenMW (daltons)Ho trRibonuclease ty b13.6003Ovalbumin42.0005Albumin huyt thanh nga69.0006IgG ngi160.0007Virus khm thuc l40.000.000650

Trn phn t antigen c nhiu epitop Tnh c hiu ca antigen da vo tnh c hiu ca epitopAntigen n gi (Monotonous antigen)-polysaccharide, c mt epitop c hiuAntigen a gi (Polytonous antigen)-polypeptide, c nhiu epitop c hiuEpitop nhn din khng th (lymphocyte B) Epitop nhn din lymphocyte T Lymphocyte T nhn din epitop x l v trnh din bi MHCLin kt cho (crossing linking): 2 antigen c mt hay nhiu epitop hon ton ging nhauVaccin bnh u (human pox = cow pox)Vaccin bnh di (rabies) t no b*

5.1.3. PHN LOI(1). Da vo ngun gcAntigen vi sinh vt (vi khun, virus v cc VSV khc)Antigen khng c ngun gc vi sinh vt (antigen b mt t bo, antigen t ng)(2). Da vo cu to ho hcProtein, polysaccharide, lipoprotein, glycolipid, nucleic acid(3). Da vo s hp tc vi tuyn c Antigen ph thuc tuyn cAntigen a gi, to tr nh min dch tt, tng hiu ng th hai (antigen nhm mu, protein cy ghp, antigen virus...) kch thch min dch vi lymphocyte T helper Antigen khng ph thuc tuyn cAntigen n gi, kch thch lymphocyte B sn sinh khng th (lipopolysaccharide ca vi khun Gr -)*

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5.2.1. I CNGKhng th l nhng phn t globulin min dch (Ig) c tng hp t cc lymphocyte B v tng bo (plasma cell) c 2 c tnh:-Nhn din antigen-Kt hp c hiu vi nhm quyt nh antigen5.2.2. CU TRC PHN T2.1. Chui nh (L) v chui nng (H)-Cu trc khng gian i xng gm 2 i to hnh ch Y, mi i gm chui L v H lin kt bng cu ni disulfide (S-S)-Chui L (23 Kd) gm 2 loi l chui v , cu to khong 220 cu t amino acid; vng bin i (VL)-110aa v vng khng bin i (CL)-110aa-Chui H (53-75 Kd) gm 5 loi l chui , , , v ; t u N c vng bin i (VH)-110 aa v cc vng khng bin i (CH)-330-340 aa*

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5.2.3. CC LP IMMUNOGLOBULIN*

IgGIgMIgAIgDIgEMW(x103) 155940170185196400Cng thc phn tL22(L22)5L22L22L22(L22)2Glucid (%)2-310-128-101210-12Hm lng (%)70-757-1010-12

(1). Immunoglobulin G (IgG) IgG1(70%), IgG2(28%), IgG3(8%) v IgG4(4%) Chc nng sinh hc-Trung ho c t-Ngng kt t bo vi khun-Phi hp vi b th phn gii t bo vi khun-Opsonin ho (gn t bo vi khun ln b mt macrophage)-Di chuyn qua mng nhau thai*

3.2. Immunoglobulin M (IgM)IgM l loi khng th u tin c tng hp trong c th ng vt s sinh; ng thi xut hin trc nht khi c s kch thch ca antigen, sau thay th bng IgG.Chc nng sinh hc- Trung ho c t- Ngng kt vi khun- Phi hp vi b th phn gii t bo vi khun- Lin kt b mt cc lymphocyte B to thnh th th cho antigen c hiu*

3.3. Immunoglobulin A (IgA)-IgA huyt thanh v Ig A ngoi tit (sa, nc bt, nc mt, dch tit ng h hp, dch tit ng tiu ho, dch tit ng niu dc)-IgA1(93%) v IgA2(7%)C hot tnh khng khun cao nht, m nhn vai tr chnh trong s cm nhim vi khun*

3.4.Immunoglobulin D (IgD)-D b bin tnh bi nhit v b phn gii bi enzyme-IgD trong huyt thanh tng trong cc trng hp nhim khun mn tnh-IgD c vai tr nh th th antigen c hiu gn trn b mt lymphocyte B (mnh ui)3.5.Immunoglobulin E (IgE)-Gn ln b mt t bo Mast v basophil (Cc4), kt hp vi antigen s gii phng cc cht trung gian (histamin) gy ph n, ni mn .-Tng tnh thm thnh mch*

5.2.4. SINH TNG HP IMMUNOGLOBULIN*

-Do 2 tp on polysome khc nhau-Chui L c tng hp trc, khi c 19-22 cu t th chui H bt u c tng hp, tng hp n u s lin kt vi chui L n .-Hnh thnh cc domain-Lin kt vi cc phn t glucid-Phn tit hoc ng gi zymogen trong lymphocyte B*

5.2.5. TC NG SINH HC CA IMMUNOGLOBULIN*

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5.3.1. H thng b th (Complement system) Nhm protein huyt thanh, c hot tnh enzyme (min dch t nhin-min dch khng c hiu), b ph hy 560C trong 30 pht. Gm 9 loi protein (C1-C9) Tng hp t gan, macrophage, monocyte v lin bo lp nim mc rut Vai tr sinh hc- Hot tnh phn v (C3a v C5a)-Anaphylatoxin- Hot tnh ho hng ng (C5a)- Opsonin ho (gip cho macrophage thc bo)- Phn gii mng t bo vi khun- Kch thch lymphocyte B sn sinh Immunoglobulin- Ngn nga v loi b phc hp antigen-khng th*

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5.3.2. Phc hp ho hp m chnh (MHC - Major histocompatibility complex)- Histocompatibility antigen hay transplantation antigen MHC l nhng cu trc phn t trn b mt t bo ng vt b cm nhim, cu to l glycoprotein- Vai tr: trnh din antigen l cho tp on lymphocyte T- Gm 2 loi: MHC lp I v MHC lp II(1). MHC lp I2 chui polypeptide, chui hay chui H (43 Kdal) v chui hay chui 2 microglobulin (12 Kdal)*(2). MHC lp IIc sn xut v biu l trn b mt ca mt s loi t bo nh lin bo tuyn c (nurse cell), t bo thn kinh nh (microglial cell), t bo ni mc mch mu, monocyte, macrophage v lymphocyte B. Cu to gm chui (34 Kdal) vi 2 domain cu trc 1, 2 v chui (28 Kdal) vi 2 domain cu trc 1, 2

*MHC lp IMHC lp II

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5.3.3. Cytokine Cytokine c cu to ho hc l glycoprotein, c tng hp v sn sinh t cc t bo tham gia trong h thng min dch ca c th ng vt. Bao gm: Interferon, interleukin, tumor necrosis factor v chemokin.(1). Interferon (IFN)IFN (16-25 Kdal) c sn sinh khi t bo ng vt b cm nhim virus, rickettsia hoc protozoa.5 loi IFN: IFN - T bo hnh rng ca IFN - T bo l phi IFN - Nguyn si bo IFN - T bo l phi IFN - helper Tcell 1 IFN - T bo l phiVai tr- Chng s nhim v nhn ln ca virus trong t bo - Kch thch s thc bo ca macrophage- c ch s pht trin cc khi u*

(2). Interleukin (IL)(8-75 Kdal)Gm 18 loi IL-1 n IL-18Vai tr: iu ho s tng tc gia lymphocyte vi cc loi bch cu khc.Ngun gc: macrophage, helper T cell 1, helper T cell 2, sinh si bo, t bo bn th, lymphocyte B, CD8+ T cell, CD4+ T cell.(3). Tumor necrosis factor (TNF)(17-25 Kdal)Vai tr: Tiu dit cc t bo buNgun gc: Macrophage v lymphocyte T(4). Chemokin (8-10 Kdal)Vai tr: D phn vo phn ng vim, to ho hng ngNgun gc: macrophage, neutrophil *

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CHC NNG SINH HC CA MACROPHAGETrnh din AntigenThc bo v tiu dit vi khunTi t chc m bo v s lnh vt thngPHN TITTiu dit t bo buCytokinIL 1IL 6IL 12IL18TNF-EnzymeLysozymeProteaseCollagenaseElastasePlasminogen activatorCc yu t khcProstanoidComplementFibronectinYu t ng mu*

CHC NNG SINH HC CA ACIDOPHILO2-H2O2Phospholipase DLysophopholipaseHistaminaseCatalaseProstaglandin D2 Prostaglandin E2 Prostaglandin F2Leukotriene A-E4PAFProtein chnhEosinophil cationic proteinEosinophil neurotoxinEosinophil peroxidaseIL-1 TGF- IL-2 TGF-IL-3 TNF-IL-4 GM-CSFIL-6 PDGFIL-10IL-16IL-8MIP-1RANTECytokinCationic ProteinCht chuyn ho lipidChemokineEnzyme*

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