模式识别受体与乙肝病毒感染(英文版).ppt
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1、Dept of Infectious Diseases Shanghai Ruijin Hospital Jiaotong University School of Medicine Qing Xie,Pattern Recognition Receptors and HBV Infection,Role of Toll-like Receptors,HBV infection is still a major global health care problem,350 million chronic carriers worldwide 9th leading causes of deat
2、h 75% of HBV carrier are Asian,High prevelance,Widely spread,Nature History of HBV Infection,Acute HBV Infection,Chronic HBV Infection,Chronic Hepatitis B,Cirrhosis,Liver Failure,HCC,3-5% Adult,95% Children,5年,6-15%,5年,20-23%,5年,12-20%,Antiviral treatment,HBV Virons,Complete Response,Partially Respo
3、nse,Non Response,Immune as a key factor influences the outcome and progression of disease,Challenge: What mechanism of virus clearance of host? How to do that?,HBV,H O S T,Virus clearance,resolved,Unable to clear virus,Persistent infection,Progression of disease,Immune function of Host,Central Role,
4、Three essential elements required in liver inflammation following HBV infection,HBV VIRONS,HEPATOCYTES,IMMUNOCYTES,调节性T细胞,Antigen specific-ADAPTIVE IMMUNITY,CD8,CD4,B,Th17,Host,Virus Clearance,Host Immune Response is mediated by Pattern Recognition Receptors(PRR) which recognizes specific molecular
5、or replication intermediator of virus particles.,HBV Virons,Type I IFN Induction,Activated Cytotoxic Response,Pattern Recognition Receptors(PRR),Recent Studies found:,The close relationship between host innate immunity and the recognition of pathogen and clearance. TLR as an important PRR,plays a ce
6、ntral role in defence of virus invasion. Different TLR can recognize various pathogen.,What is a role of TLR in HBV infection?,HBV,G+bacteria,G-bacteria,Virus clearance,Disturbance of TLR expression induces the persistent infection. Abnormal of signal passway initiated by TLR induces the inability t
7、o clear HBV or overclearance, that leads to immunotolerance or immune injury.,Toll-like receptor (TLR)-mediated recognition of specific structures of invading pathogens initiates innate as well as adaptive immune responses via antigen-presenting cells (APCs). DC represents the most potent antigen-pr
8、esenting cells and thus plays an important role in the induction of innate and specific immune response.,Requirement of DC involment in TLR-initiated antivirus response,Distribution of TLR on DCs,mDC: (myeloid dendritic cell,mDC) ( CD3、CD14、CD16、CD19、CD20、CD56) BDCA1(CD1c)+ CD11c+ TLR1 TLR2 TLR3 TLR
9、4 TLR5 TLR6 TLR8 pDC:(plasmacytoid dendritic cell, pDC) ( CD3、CD14、CD16、CD19、CD20、 CD56)BDCA2+ BDCA4+ CD123+ TLR7 TLR9 TLR3、TLR7、TLR9 参与抗病毒免疫,Scientific Questions?,Function of Myeloid and Plasmacytoid Dendritic Cells of Patients with CHB? Expression of TLR-3, TLR-9 in patients following HBV chronic
10、infection?,CHB: 28 cases Healthy:22 cases,Study Populations,Including criteria: (1) Serum HBsAg positive 6 months. (2) Abnormal liver function for 2 times with 2 weeks apart, ALT1.5 xU/L at screeing. (3) Serum HBeAg(+),HBeAb(-). (4) Serum HBV-DNA1105 /L. (5) excluded liver cirrhosis by liver ultraso
11、und (6) excluded HIV、HCV、HDV、HEV coinfection. (7) Not allowed to use antiviral treatment or immunmodulator within 6 months.,Selection and preparation of pDC、mDC,pDC BDCA4 DC isolation kir,mDC BDCA1 DC siolation kit,Fig.3. TLR9 expression of isolated peripheral precursor pDCs of chronic HBV patients
12、(n=28) and healthy controls (n=18). (A) No difference in the percentage of pDCs expressing TLR9 was found between the patients and the controls. (B) The MFI of TLR9 from patients were significantly reduced compared to controls. Data are expressed as meanSD,0,25,50,75,100,125,patients,n=28,controls,n
13、=18,p0.05,positive cell %,0,100,200,300,400,500,600,p0.05,patients,n=28,controls,n=18,MFI,Fig.4. Flow cytometric analysis for enumeration of pDCs. PBMCs were isolated and stained with the following antibodies:Lin-FITC( CD3,CD14, CD16,CD19,CD20,CD56), PE-BDCA-2, and APC-CD123. (A) Dead cells were exc
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