乙型肝炎临床免疫学特点和临床转归的相关性研究.ppt

乙型肝炎临床免疫学特点和临床转归的相关性研究
解放军第三○二医院
王福生
2012-4-27
2
医生的追求!
病人的福气!
有效的药品
科学的方案
病人的依从
3
医学
看病
Study
实验室
临床
没有研究、没有医学
4
Important Functions of the Liver
Hemostasis
Synthesis
Storage
Excretion
Filtration
Immunity
Tzanakakis/Hu, Annu Rev Biomed Eng 2000
我国是乙肝大国,慢性乙肝易发展为肝硬化、肝衰竭和肝癌,严重危害军民健康。
Rehermann B. Nat Rev Immunol, 2005 王福生. Expert Rev Gastro Hepatol, 2009
研究背景和目的
乙肝是病毒性疾病
病毒学指标: HBV DNA、乙肝五项…
乙肝更是免疫性疾病
免疫学指标:空白
HBsAg阳性:

慢性乙肝:
2500万人
死于相关疾病:
30万人/每年
每年治疗费用:
1000亿元
免疫应答
王福生. Hepatol Res 2007; Exp Rev Gastro Hepatol 2009
控制病毒
免疫损害
病毒感染
急性乙肝
慢性乙肝
肝硬化
肝癌
三部曲
HBV
肝细胞
乙肝进展和转归:三驾马车
3. Antiviral Therapy
Decreased viral load.
Active HBV replication
after infection.
Viral Replication > Clearance
Increased viral load.
2. Host Immunities inhibit
VR and clarify virus
Viral Replication = Clearance
Balance of blood viral load
Viral replication and host immunity
Liver
Host immunity
Virus in circulation
Virological characteristics during chronic HBV infection
Viral reservoir
cDNA
The persistent HBV replication
The accumulation of HBV antigens in vivo
Characteristics in liver pathology in chronic hepatitis B
Lymphoctyes
Plasma cells
Macrophages
Fibrosis
Liver cirrhosis
Degradation
Necrosis
Atalas of the Liver, Maddrey WC, 3rd Edition
Inflammation
infiltration
NK and Kuffer cells
activated HSC
Epithelial cells
T cells
NK, MΦ,
Treg, PD-1
HCC
Impairment of specific T cells
Impairment & Disorder of immune responses in CHB patients
Impairment of Ag presentation
Abnormal B-cell responses
Suppressive
factors increased: Treg and PD-1
Hyper-activated NK, Th17 immunity inducing liver injury
Specific Immune
Responses 
Non-Specific Immune
Responses 
Host Immune
Disorder
B cell
T cell
Th17 cell
Treg cell
NK cell