免疫刺激剂.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,*,天然免疫系统的主要成员,补体系统complement,溶菌酶,lysozyme,干扰素,interferon，IFN,转铁蛋白,transferrin,巨噬细胞,macrophage,嗜中粒细胞,neutrophils,自然杀伤细胞,natural killer cells,适应性,免疫系统的主要成员,B淋巴细胞与抗体,辅助T淋巴细胞（Th cells),与细胞因子（cytokines),细胞毒性T淋巴细胞,（cytotoxic T cells,CTL),P,P,感染的细胞,P,P,P,激活的,补体系统,自然杀伤细胞,激活的,NK,巨噬细胞,激活的,M,MAC,MAC,C3b,C3b,免疫刺激剂,Immunostimunants,Synthetic chemicals,Levamisole,FK-565,Biological substances,Bacterial derivatives,Animal and plant extracts,HCl,Levamisole,Anthelminthic drug,In mammals,metabolic and phagocytic activities of neutrophils,number of phagocytes and leucocytes,level of lsozyme in serum,In Coho salmon and Carp,Injection of levamisole,+,modified Freunds complete adjuvant increased Coho salmons resistance to,A.salmonicida.,Injection of levamisole increased the phagocytic activity and myeloperoxidase activity of neutrophils,leucocyte numbers and serum lysozyme levels in carp.,In,Rainbow trout,Injection of levamisole（0.1-0.5mg/kg）,Resistance to,Vibrio anguillarum,Phagocytic activity and chemiluminescance responses of leucocytes,NK cell activities,Concentration of complement,No effects with h,igh dose（5mg/kg）,Effects,of,levamisole on fish,Spleen cells,Phagocytic activity,NBT reaction,Number of antibody-producing cells,High dose,No stimulation,Completely suppress,Oral administration of,levamisole,Leucocyte numbers,Serum lysozyme levels,The stimulated NBT reduction and phagocytic index of phagocytic cells,Immersion of,levamisole,Carp in 10ug/ml for 24h,Resistance to,A.hydrophila,Chemotactic ability of phagocytes,Phagocytic activity and chemiluminescence,Rainbow trout in 5ug/ml for 30min,Phagocytic activity and index,Specific antibody titers 2min later in,A.salmonicida,O-antigen bacterin,FK-565,FK-156,Lactoyl tetrapeptide,isolated from cultures of,Streptomyces olivaceogriseus,is,a,ctive against microbial infection in mice.,FK-565 is the synthetic derivative of FK-156.,Heptanoyl-y-D-glutamyl-(L)-meso-diaminopimelyl-(D)-alanine，庚酮-谷氨酸-内消旋-二氨基庚二基-丙氨酸,FK-565 in Rainbow trout,Injection of FK-565,Resistance to,A.salmonicida,Activation of phagocytic cells,Injection of FK-565 with,Y.ruckeri,O-antigen or,A.salmonicida,O-antigen,Number of splenic antibody-producing cells,Specific antibody titers,Polysaccharides,-,glucan,Chitin,Chitosan,Oligosaccharide,Lentinan,Schizophyllan,Beta-1,3-D glucan,Zymosan,酵母聚糖,The nude cell wall of,saccharomyces cerevisiae,1940s Dr.Pillemer Louis,Anti-tumor effect in mouse,Proteins,lipids and other impurities,Toxity and side-effects,Zymocell,Purified,-,1,3-D glucan,Anti-diabetes,Anti-high-lipids,Anti-infection after high risk operation,Increase of marrow and white blood cells after lethal radiation,purity,85%or higher,slightly beige,very fine particulate,free from proteins and lipids,-,Glucan,genuine,Mechanism of Uptake,Particulates of,2 um in diameter,could be easily,engulfed by,macrophages.,Beta Glucan Enhances Four Keys Immune Responses,Production of white blood cells that destroy pathogens.,Cellular mobilization WBC to the site of a foreign challenge.,Phagocytic capacity or the ability to engulf non-self cells.,Production of reactive oxygen intermediates and other agents that kill the foreigners.,Beta Glucan StimulatesPost-Radiation Hematopoietic Recovery in Mice,Beta Glucan StimulatesPost-Radiation Hematopoietic Recovery in Mice,-,1,3-D glucan Increases Phagocytic Capacity of Human Innate Immune Cells,多糖的分子量,8kDa,500kDa,多糖的分枝度,分支度在,0.2,0.33,抗肿瘤的,效果最佳。,Beta Glucan in aquaculture,与体液因子及免疫细胞的特异受体结合,15-30mg/kg体重或0.5-1g/kg饲料,In fish,促进M向病灶转移，ROS,，,抗病毒、抗应激,显著提高疫苗效价,In shellfish,PO（酚氧化酶原系统）activity,通过多种途径参与机体的防御反应,附：虾蟹贝类的免疫系统,Hemocytes,pro,phenoloxidase,phenoloxidase,PO,氧化酪氨酸、,二羟基苯丙氨酸等,生成苯醌中间产物,最终生成黑色素,Oyster hemocyte,Peptidoglycan&Lipopolysaccharide,Peptidoglycan,Mechanisms of,Peptidoglycan,In vertebrates,Activate T&B lymphocytes,Activate phagocytes,Activate complete system,通过血小板溶解释放多种药理活性物质,诱发抗体的产生和补体的生成,Effects of Peptidoglycan in aquaculture,混饲（,6-60mg/kg,体重或,0.2-2g/kg,饲料）,降低条件致病菌感染引起的死亡率，预防病毒感染，防御寄生虫侵袭。,与抗生素合用具有协同作用。,作为疫苗的佐剂增强抗原细胞的信号分子被有效呈递，促进淋巴细胞产生抗体。,促进机体生长，提高生长率、存活率、饲料利用率。,Effects of Peptidoglycan in Fish,从嗜热双歧杆菌（,Bifidobacteriumthermophilum,）细胞壁中提取的肽聚糖，,提高,虹鳟,（,Oncorhynchusmykiss,）对弧菌病、五条鰤（,Seriolaquinqueradiata,）对链球菌病和日本对虾（,Penaeusjaponicus,）对弧菌病与病毒性血症的抵抗力。,Effects of Peptidoglycan in Shrimp,促进小颗粒细胞脱粒、抗菌肽的分泌,激发细胞黏附、包囊作用,促进ROS生成,提高透明细胞的吞噬功能,激活丝氨酸蛋白酶原，激活酚氧化酶系统。,Lipopolysaccharide,LPS,脂多糖,Mechanisms of,LPS,淋巴细胞有丝分裂原,巨噬细胞激活剂，M ROS,嗜菌作用,刺激对虾防御细胞的功能（嗜菌、黑色素沉着、包囊和凝结）,注射0.01-0.05mg/kg体重,混饲6-60mg/kg体重或0.2-2g/kg饲料,LPS,of,A.stenohalis,Achromobacter stenohalis,isolated from sea water.,In mouse,macrophages,B-lymphocytes,Anti-tumor effects,In white-spotted char Inject with inactivated,A.stenohalis,Chemiluminescent responses of kidney cells,Complement activation,Resistance to,A.salmonicida,challenge,Muramyl dipeptide,MDP,胞壁酰二肽，Derived from,Mycobacterium,In coho salmon:injection of MDP+modified Freunds incomplete adjuvant，47-fold increase in resistance to,A.salmonicida,In,rainbow trout,:injection of,MDP-Lys,Phagocytic activities,respiratory burst and migration activities of kidney leucocytes；Resistance to,A.salmonicida,Chitin and Chitosan,Effects of chitin and chitosan in Fish,Injection,immersion or oral administration,Chitin,Rainbow trout Phagocytic activity，Resistance to,Vibrio anguillarum，,yellowtail Resistance to,P.piscicida,Adjuvant effects,Chitosan:de-N-acetylated chitin,Rainbow trout，NBT，myeloperoxidase，total Ig concentration,brook trout Resistance to,A.salmonicida,