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SÖÏ HÌNH THAØNH MOÄT ÑAÙP ÖÙNG MIEÃN DÒCH • GS Phaïm Hoaøng Phieät • BS Huyønh Thanh Bình 1 Ñoäng hoïc moät ñaùp öùng mieãn dòch . . 2 So saùnh ñaùp öùng thì 1 vaø thì 2 ÑÖMD Thì 1 Tính chaát Tieàm aån Dieãn Taêng SLKT tieán Bình oån Giaûm suùt Thì 2 1-2 tuaàn 3-5 ngaøy Taêng nhanh Taêng raát nhanh 2-3 tuaàn Nhieàu thaùng- naêm Nhanh Töø töø Soá löôïng Cao hôn thì 1 nhieàu Lôùp KT Chaát löôïng Aùi löïc vôùi KN IgM IgG + +++ 3 Teá baøo trình dieän khaùng nguyeân HLA lôùp II –TCD4 (peptid 15-34 aa) HLA lôùp I –TCD8 (peptid 9 aa) 4 Class I MHC Pathway Peptide is presented by MHC-I to CD8 cytotoxic T cell Plasma membrane Peptide passes with MHC from Golgi body to surface Viral protein is made on cytoplasmic ribosomes Globular viral protein - intact Peptide associates with MHC-I complex rER Proteasome degrades protein to peptides Peptide transporter protein moves peptide into ER Golgi body Peptide with MHC goes to Golgi body MHC class I alpha and beta proteins are made on the rER 5 Class II MHC Pathway Peptide MHC-II complex is presented to CD4 helper T cell Endosome fuses with plasma membrane Immunodominant peptide binds to class II MHC Golgi body Globular protein CD4 helper T cell Endosome Fusion of endosome and exocytic vesicle Endocytosis Lysosome Exocytic vesicle fuses with endosome releasing Ii from αβ dimer Protein is processed to peptides in endosome or lysosome Class II MHC α Synthesis 3 chains: α,β and Ii β Ii 6 Endoplasmic reticulum Hoaït hoùa Lympho T ÑTB,Tc, (B) 4 IL2 (IL4) 3 2 1 7 Points Concerning Antigen Processing and Presentation 1. Location of pathogen • viruses in cytosol, MHC class I pathway, Tc response • extracellular bacteria, MHC class II pathway, Th2 response, Ab formation • intracellular bacteria, MHC class II pathway, Th1 response 8 Points Concerning Antigen Processing and Presentation 2. Peptides derived from both self and non-self proteins can associate with MHC class I and class II molecules. 3. Chemical nature of MHC groove determines which peptides it will bind. 9 Hoaït hoùa Lympho baøo T Tín hieäu KN Tín hieäu thöù 2 B (1)Ti (TCR) KN (2) CD4 (TH) HLAII(APC) sIg (BCR) KN (1) IFN- (TH) (2) IL1 (APC) IL2,IL4, IL5 10 Hoaït hoùa Lympho B 11 Söï hôïp taùc giöõa Ñaïi thöïc baøo, lympho T vaø lympho B 12 Cellular Events in 1o Response to T-dependent Ags • Lag – Clonal selection • Log 1o Ag – IgM – Class switching • Stationary • Decline • Memory Cell Pool IgM IgG Memory Cells 13 Cellular Events in 2o Response to T-dependent Ags • Lag phase – Virgin cells – Memory cells Virgin B cell • Log phase IgG – Pool size – IgG, IgA or IgE • Stationary • Decline – Sustained production IgM Memory Pool Memory Cells IgG 14 Memory Cells Hieäu öùng Hapten-taûi Hapten khoâng coù tính gaây MD Hapten phaûi gaén vôùi 1 protein taûi => phöùc hapten taûi (hapten-carrier complex) Th nhaän dieän taûi, B nhaän dieän hapten Taûi ôû thì 1 vaø thì 2 phaûi gioáng nhau. 15 Söï hôïp taùc haïn cheá trong nhoùm phuø hôïp moâ (hieän töôïng Zinkernagel vaø Doherty) Mouse Strain A or B Mouse Strain A or B Immunize with antigen Period of 7 days Peritoneal macrophage Antigen T cells isolated from lymph nodes T cell primed with antigen Macrophages and T cells are co-cultivated Macrophage presents antigen Anti X-induced Macrophage T-cell proliferation Assay DNA synthesis after 48 hr Strain A Strain A Strain B Strain B A B B A yes no yes 16 no Tc Cell Self MHC Restriction Mouse Strain A or B Mouse Strain A or B Immunize with virus Purify Fibroblasts Period of 7 days Isolate spleen Virus-specific cytotoxic T cells (CTLs) isolated from spleen 51Cr labeled fibroblast presents antigen Spleen Fibroblast 51Cr release CTLs (target cells) from fibroblasts immunized infected (lysis) with with Virus-specific CTLs CTLs and fibroblasts are co-cultivated Infect fibroblasts with virus and radiolabel with 51Cr Assay 51Cr release Strain A Strain A Strain B Strain B A B B A yes no yes 17 no Self MHC Restriction in the Thymus 4 low 8 low 48 low Productive TCR rearrangement 4+ 8 + TCR Sub-capsular region Non-productive TCR rearrangement Not recognise self MHC APOPTOSIS Recognise self MHC TCR recognises 4+ 8 + self antigens TCR TCR does not recognise self antigens Negative selection 4- 8 - macrophage Cortex Cortico-medullary region 4+ 8 + TCR Medulla vessel 4+ 8 TCR 4- 8 + TCR 18 KN khoâng leä thuoäc thymus  Caáu truùc: ñaïi phaân töû do truøng phaân caùc ñôn vò nhoû (lipopolysaccharide, dextran…)  Caùc epitop gioáng nhau treân ñaïi phaân töû lieân keát vôùi nhieàu sIg taïo thaønh ñaùm (hieän töôïng ñoäi muõ) => hoaït hoùa Lympho B thaønh töông baøo => SX KT  KT thuoäc lôùp IgM, khoâng taïo ra trí nhôù MD 19 Hieän töôïng ñoäi muõ 20
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