新生猪惊人的免疫系统

The Amazing Immune System in the Neonatal Pig 新生猪惊人的免疫系统 Tom Molitor 汤姆莫利特博士莫利特博士 University of Minnesota 明尼苏达大学 molit001umn.edu Leman China,October 13-15,2013,Xi”an Amazing Immune system in the neonatal pig 新生猪惊人的免疫系统:Outline大纲 Differences in Immune system in the pig.猪免疫系统的差异 Developmental Immunity in the pig 猪免疫功能的发育 Vaccination of the Neonatal Animal 新生动物的疫苗接种 Passive Immunity被动免疫:Pros and cons 优点和缺点 Cross-fostering affects immunity交叉寄养影响免疫力 Maternal Interference?母抗干扰？Summary总结-Applications应用 Rationale思考/对比/分享 PEDV,PRRSV,FMDV,PPV,Mycoplasma,Protection,recovery,dependent on the immune system.PEDV,PRRSV,FMDV,PPV,支原体，保护，恢复，对免疫系统的依赖。Maternal interference,ineffective vaccination,Immunosuppression,stress,disease,all resulting from an ineffective immune response.母抗干扰，无效疫苗接种，免疫抑制，应激，疾病，都源于无效的免疫反应 The Immune system is highly important for the health and welfare of swine.免疫系统对猪的健康和福利来说是非常重要的。Swine have a number of profound differences in the Immune system including anatomical,physiological,cellular and from a functional response.猪有一些免疫系统的深刻差异，包括解剖，生理，细胞和功能反应。Your task is.你的任务是.Think/Pair/Share思考/对比/分享 Provide at least three differences in the immune system of a pig compared to human(or the classic animal model-mice)?相比于人类（或经典的动物模型-老鼠），提供至少三个猪免疫系统的不同点 Differences in Immune system 免疫系统的差异?Development of Immunity免疫力的发育 Fetus胎儿 Neonate新生儿 Weaned pig断奶猪 Why does the piglet need maternal Immunity?仔猪为什么需要母体的免疫力？Epitheliochorial placenta 上皮绒毛膜 胎盘 The multi-layered placenta in pigs prevents the transit of maternal Ig into the fetus 多层猪胎盘防止母体lg运输到胎儿(Butler,1998;Salmon,1999).The placenta is a sterile environment 胎盘是一个无菌的环境 Sterzl et al 1966,Porter 1988 Neonatal Piglet immunologically nave 新生仔猪是无免疫的 Immune system develops 70 d of 116 total of gestation for the pig,third trimester for all 猪免疫系在总共夫人116 天妊娠统发育70天 New born is Immature,not incompetent 新生猪不成熟，不是无能 Adkins et al 2005 Relationship of Placental Type to Maternal Immunity Transfer胎胎盘类盘类型与母体免型与母体免疫疫传递传递的关系的关系 Immunoglobulin Transfer Type of Placenta In utero Colostrum Species Epitheliochorial None 100%Horse,cow,pig,sheep Endotheliochorial 5-10%90-95%Dog,cat Hemochorial 90%10%Primates,rodents How is immunity transferred?细胞介导的免疫转移？胎胎盘类盘类型型 免免疫疫传递传递 种类 子宫内 初乳 上皮上皮绒绒毛膜毛膜 马，牛，猪，羊 狗，猫 灵长类动物，啮齿类动物 绒绒毛膜受血毛膜受血 内皮内皮绒绒毛毛 Colostrum初乳 The perfect Food-colostrum 完美的食物-初乳！!ImmunePlus with colostrum 7505 初乳7505 ImmunePlus Elixir of life 仙丹仙丹 Daniel Clark in Colostrum lifes first food:“Bovine Colostrum rebuilds the immune system,destroys viruses and bacteria and fungi,accelerates healing of the body tissue,helps loose weight,burn fat,increase bone and lean muscle mass and slows down and even reverses aging”丹尼尔克拉克在初乳生命的第一食物中提到：“初乳重建免疫系统，破坏病毒和细菌和真菌，加速身体组织的愈合，有助于减轻体重，燃烧脂肪，增加骨骼和肌肉质量，减慢甚至逆转老化“Absorption of colostrum components is critical for piglet survival 吸收初乳成分是仔猪存活的关键 Epitheliochorial placenta 上皮绒毛膜胎盘 The piglet is immunologically nave and immature 仔猪无免疫能力并且不成熟 Need for colostrum 需需要初乳要初乳:Colostrum deprivation and survival to 90 kg 无初乳无初乳和和生存至生存至90kg的关系的关系 生存 出生断奶 24小时断奶 Colostrum components初乳成分 Hosea Blewett et al.,2008 Wagstrom et al.,2000 Salmon et al,2008 Le Jan,2004 Colostrum初初乳乳=first milk首次乳汁首次乳汁 免疫球蛋白 溶菌酶 乳过氧化物酶 核苷酸水解抗体 K-酪蛋白-乳球蛋白 结结合咕啉合咕啉 粘蛋白 奶中的乳铁蛋白 抗分泌外源凝集素 自由分泌成分 低聚糖 脂肪酸 母体白细胞和细胞因子 sCD14 补体及补体受体-防御素1 Toll样受体 双歧因子 益生元 Immunoglobin in sow colostrum 母猪初乳中的免疫球蛋白 Klobasa et al.,1987 Straw et al.,1999 相对浓度 泌乳日 哺乳期母猪乳浆中IgG,IgM及IgA浓度 泌乳阶段 Approach途径 Sow Periphery 母猪外周 Mammary Gland(MG)乳腺 Piglet仔猪 Samples 样品 Sow Blood 母猪血液 Sow Colostrum 母猪初乳 Piglet blood pre colostrum ingestion 摄入初乳前仔猪血 Piglet blood after colostrum ingestion 摄入初乳后仔猪血 Endpoints终点 Total IgG and IgA via ELISA 通过ELISA总的IgG和IgA Total mononuclear cells 单核细胞总数 CD4,CD8,T lymphocyte phenotyping via flow cytometry通过流式细胞仪CD4,CD8,淋巴细胞表型 Immunoglobulin G and A in sow serum and colostrum母猪血清和初乳中的免疫球蛋白G和A 0 1 0 2 0 3 0 4 0 5 0 6 0 S o w s e r u m C o l o s t r u m I g G I g A Immunoglobulin(mg/ml)n=16 Variation:SEM Maternal derived immunity 母源免疫:In the sow vs the neonatal pig?在母猪vs新生猪？Bandrick et al 2010 免疫球蛋白 母猪血清 初乳 Maternal immunoglobins are beneficial to the newborn pig母体免疫球蛋白有利于仔猪 Maternally-derived antibody-mediated immunity(AMI)is protective母体介导的免疫是有保护性的 PCV-2 猪圆环病毒-2;Opriessnig et al.,2008 SIV 猪流感病毒;Loeffen et al.,2003 B.pertussis 百日咳博德特氏菌;Elahi et al.,2006 CSF 猪乙脑病毒;Parchariyanon et al.,1994 TGEV 猪传染性胃肠炎病毒;Sestek et al.,1996 Pseudorabies 伪狂犬病;Kritas et al.,1997 Janeway,2005 Relative immunoglobin concentration in piglet serum pre and post colostrum ingestion仔猪摄入初乳前后血清免疫球蛋白相对浓度 PS=Pre Suckle 哺乳前;AS=After suckle 哺乳后 Neither IgG nor IgA were detectable by ELISA in PS serum 哺乳前血清用哺乳前血清用ELISA检测检测不到不到IgG或或IgA Bandrick et al 2010 Ig concentration mg/mL IgG PS IgG AS IgA PS IgA PS Ig浓浓度度 Cells in Sow Colostrum母猪初乳中的细胞 6.32E+06 1.48E+06 1.76E+06 2.75E+05 1x107 cells/mL Wagstrom et al.,2000 Total number of cells/m 细细胞胞总总数数/ml 70-90%are T cells 70-90是T细胞 巨噬细胞 中性粒细胞 巨噬细胞 淋巴细胞 上皮细胞 泌乳日 中性粒细胞 淋巴细胞 上皮细胞 T lymphocyte distribution in sow bloo