医学部医学科2年 免疫学講義 10/26/201 - Kurume U

1 10/26/201 - : T T T Ag TCR T Ag MHC class II cells (green) lysosome (red) Lysosome: an organelle in the cytoplasm of eukaryotic cells containing degradative enzymes enclosed in a membrane +++ Janeway s 7 332, +++ Dendritic Cell: DC) Uematsu S, et al. Nat Immunol 2006, 2008 1) TLR5 CD11c DC 2) CD11c DC CD11chigh CD11bhigh DC TLR5 3) DC IgA Th1 Th17 TLR5 CCR7 : T +++ MHC class II I (+) MHC: Major histocompatibility complex HLA (clonal expansion) T CD11c T Immunologic Synapse T SMAC.

2 Supramolecular activation complex T T T cell APC 15nm Lipid Raft T p-SMAC( ) d-SMAC( ) c-SMAC( ) TCR: T ( ) CD4 CD2 CD45, CD44 CD43 Central Peripheral Distal Janeway s 7 342, 3 2) MHC 3) 4 5 Janeway s 7 335, -like Receptor (TLR) PAMPs (LPS) RNA TLR4 TLR3 ( ) TLR7 ( ) TLR9 ( ) TLR5 CD14, MD-2 ( ) ( ) ( ) CpG DNA CpG DNA TLR1/TLR2 TLR6/TLR2 RNA Ribosome Nucleoid Flagellin DEC205.

3 In vivo Janeway s 7 336, D -SIGN CD209 : , MHC ICAM-1, ICAM-2, LFA-1, DC-SIGN, CD58 Janeway s 7 336, DC) B MHC II CD4 : Ag (APC) T cell CD28 B7 2 CD4 T CD8 T (CTL) Janeway s 7 352, : (IL-6, IL-12, TGF ) APC CD28: CTLA4: PD-1: Genetics Institute (Cambridge, MA) DFCI: Dana-Farber Cancer Institute and Harvard Medical School (Boston, MA) Co-stimulatory molecules: ( ) CD.

4 Cluster of Differentiation PI3K Akt Vav1 PKC CARMA1 MALT1 Bcl10 P65 p50 IKK IKK IKK NF B DNA T TCR CTLA-4, PD-1 T ( , ) PD-1L PD-1 CD28 CTLA4 CD80 CD86) CD80/CD86 CD80/CD86 MHC TCR CD28 CTLA4 -1/ PD-1 ligand APC PD-1 ligand (PD-L1, PD-L2) PD-1 (Progammed cell death-1) Genetics Institute (Cambridge, MA) DFCI: Dana-Farber Cancer Institute and Harvard Medical School (Boston, MA) 1992) PD-L1: (2000) PD-L2: DFCI (2001) PD-1/PD-L1 CTL PD-1 PD-1 PD- PD- L1 PD-1 nivolmab) 5 12 CCL21 CXL12 CCR7 High Endothelial Venules.

5 HEV T HEV) L- - - LFA-1=CD11a/CD18= L/ 2 ICAM1 (CD54) Janeway s 7 327, (CD8 ) Cytotoxic lymphocytes (CTL) MHCI ( ) Janeway s 7 352, IL-2 CD4 T T helper (Th) IL-2: T NK IL-4: B IgG1, IgE Th1 IL-5: IL-9: IL-10: IL-17: , IL-21: T IL-22: IFN- : IgG MHC Th2 TNF- , TGF- : IgA Janeway s 7 353, APC FOXP3 ROR T T-bet GATA-3 IL-4, IL-5, IL-13 Janeway s 7 324, T CBT 1 A.

6 B. C. D. E. CBT A. B. C. D. E. CBT A. B. C. D. E. CBT 1 A. B. C. D. E. CBT 1 A. B. C. IL-1 D. IFN- E. IL-18 IL-10, IL-27 CBT 1 A. B. C. D. E. CBT 1 A.

7 B. C. D. E. Thank you for your attention! Any questions? Please contact me at