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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
University of Minnesota 明尼苏达大学
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 naïve 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胎盘类型与母体免疫传递的关系
How is immunity transferred?? 细胞介导的免疫转移？
胎盘类型 免疫传递
种类子宫内 初乳
上皮绒毛膜 马，牛，猪，羊
狗，猫
灵长类动物，啮齿类动物 绒毛膜受血
内皮绒毛
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
¡Daniel Clark in Colostrum life’s 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 naïve and immature 仔猪无免疫能力并且不成熟
Need for colostrum 需要初乳:Colostrum deprivation and survival to 90 kg 无初乳
和生存至90kg的关系
生存
出生断奶
24小时断奶
Colostrum components初乳成分
Hosea Blewett et al., 2008Wagstrom et al., 2000Salmon et al, 2008Le Jan, 2004
Colostrum初乳= first milk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α-乳球蛋白结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β-防御素1Toll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
üSow Blood 母猪血液
üSow Colostrum 母猪初乳
üPiglet blood pre colostrum ingestion 摄入初乳前仔猪血
üPiglet blood after colostrum ingestion 摄入初乳后仔猪血
Endpoints终点
üTotal IgG and IgA via ELISA通过ELISA总的IgG和IgA
üTotal mononuclear cells 单核细胞总数
üCD4, CD8, T lymphocyte phenotyping via flow cytometry通过流式细胞仪CD4, CD8, T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
10
20
30
40
50
60
Sow serum Colostrum
IgGIgA
Imm
unog
lobu
lin (m
g/m
l)
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ELISA检测不到IgG或IgA Bandrick et al 2010
Ig con
centratio
n mg/mL
0
10
20
30
40
50
60
70
80
90
0 1 2 3 4 5
IgG PS IgG AS IgA PS IgA PS
Ig浓度
Cells in Sow Colostrum母猪初乳中的细胞
63.214.8
17.62.75 PMN
Macrophagelymphocyteepithelial cell
> 1x107 cells/mL
Wagstrom et al., 2000
Total number of cells/m 细胞总数/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 blood and colostrumT淋巴细胞在母猪血液和初乳中的分布
Black黑色: colostrum初乳
Dark Gray深灰色: Blood血
Light Gray浅灰色: negative control阴性对照
Variation变异: SEM均值标准误
A
B
% m
onon
ucle
ar
cells
0
10
20
30
40
50
60
Sow blood Colostrum
% mon
onuclear cells
单核
细胞
百分
数CD8CD4a
b
ab
Even
t cou
nts
Neg BloodColostrumCD8
Neg
Colostrum
CD4Blood
Neg
Blood Colostrum
c
a,b
母猪血 初乳
Lumen管腔 Circulation循环
Epithelial Surface上皮表面
Ig- dam
Ig- diff dam
Ig- bovine
DAM
killed
diff sow
bovine牛
死亡的
母猪
Intestinal absorption of lymphoid cells in pigs猪淋巴细胞的肠吸收
§ Maternal derived live cells母源活细胞---yes是§ Allogeneic cells, other dam异体细胞，其他母猪---no否§ Heat killed maternal cells热灭活母体细胞----no否§ Bovine derived cells in pigs猪的牛源性细胞----no否
Tuboly and Bernath 2002Tuboly et al 1988Williams P 1993Reber et al 2008
• Does the absorption of colostrum affect immunity?初乳的吸收影响免疫力吗？
A. The lymphocyte migration across the neonatal intestine is source dependent 淋巴细胞在新生肠道转移是依赖来源的
A No cells 无细胞
B . Non mother 非母体
C. Mother cells 母体细胞
Jejunum intestinal section空肠段
Elmubark et al 2013
B. The transfer of lymphocytes across intestinal epithelium is colostral cell specific. 淋巴细胞肠上皮的转移具有初乳细胞特异性
A No cells 无细胞 B. PBMNCC. Mother cells 母体细胞
Function of Colostral T lymphocytes初乳T淋巴细胞功能
Proliferation 增殖 : Mitogens 有丝分裂原
Le Jan 1994*Williams 1993*Evans 1982*
Mixed Leukocyte Reaction 混合淋巴细胞反应
Reber et al 2005 #
Activation of neonatal APC 新生儿APC的激活
Reber et al., 2008 #Donovan et al., 2007 #
Toxicity 毒性 : Bactericidal/Fungicidal 杀菌/杀真菌
Ho & Lawson 1978= Robinson et al 1978=
Proliferation 增殖 : Bacterial antigens细菌抗原
Park et al, 1992* Viral antigens病毒抗原
Ogra & Ogra 1978*Parmeley 1976*
Colostral Tlymphocyte
初乳T淋巴细胞
Innate Immunity先天免疫 Adaptive Immunity适应性免疫
CD11a CD11c CD14
Macrophage巨噬细胞
Delayed-Type Hypersensitivity 迟发型超敏反应
Schlesinger & Covelli, 1977+
MHC I CD25CD26
Activation of neonatal lymphocytes新生儿淋巴细胞的激活
Reber et al., 2008#
Le Jan 1996*Bertotto et al., 1996+
Sirota et al., 1995*IL-2
B-cell:B细胞Isotype switching同型交换
Cytokine Production细胞因子的产生
Ngyuen et al., 2007*Le Jan 1996*Kohl et al 1982+
Pro-inflammatory TNF, IL-1, IL-6
Anti-inflammatory TGF- , IL-10
Th-1 response promoting IFN- , IL-12
Th-2 response promoting TGF- , IL-4
References Species参考物种: * Swine猪 # Bovine牛 + Human人 = Murine鼠
Post natal protection出生后保护•The first post natal protection of piglet is provided by colostrum and milk. 产后仔猪的首次保护由初乳和奶提供
•This protection is the function of timing and quality of colostrum保护受时间和初乳质量影响
IgG and IgA in piglet serum piglet before and 24 h after colostrum ingestion摄入初乳
前和24 h后仔猪血清IgG和IgA
0
5
10
15
20
25
Pre-suckling After-suckling
IgGIgA
Imm
unog
lobu
lin (m
g /m
l)
n=35
Variation: SEM
免疫球蛋白
哺乳前 哺乳后
T lymphocyte subsets in piglet blood before and 24 h after colostrum ingestion摄入初乳前和24 h后仔猪血液中的T淋巴细胞亚群
Perc
ent (
%) P
BMC
Variation: SEM
0
5
10
15
20
25
30
Pre-suckling After-suckling
CD8CD4
4.4 +/- 0.73x106 cells/ml 7.0 +/- 0.71x106 cells/ml*
p<0.01
百分数
哺乳前 哺乳后
Conclusions 结论§Maternally-derived Ig and lymphocytes are transferred to piglets母源Ig和淋巴细胞传递至仔猪
There is no selectivity in Ig transfer into piglets Ig转运至仔猪无选择性 There is selectivity in lymphocyte transfer into piglets淋巴细胞转运至仔猪有选择性
§Colostral lymphocytes are functional初乳淋巴细胞是功能性的
Integration of immunity综合免疫力: transfer from sow to piglet从母猪转移到仔猪
Sow Periphery母猪外周
Mammary Gland (MG) 乳腺
Piglet仔猪
Antibodies 抗体 (IgG, IgM, IgA): blood & MG血&乳腺
IgG, IgM, IgA from so serum; concentrated via Fc-R in MGIgG, IgM, IgA来自血清，通过FcR集中在乳腺中
IgA, IgG, IgM locally produced in the MG under hormonal control 在激素控制下IgA, IgG, IgM在乳腺局部生产
Transfer via intestinal FcRn; Peripheral or local protection 通过肠道FcRn转移; 周围或局部保护
Lymphocytes 淋巴细胞 (T & B): mucosae粘膜
MadCam-1, CCL25 VCAM-1, CCL28 Unknown transfer mechanism; Mucosal & Lymph node 未知的传输机制; 粘膜及淋巴结
Bourne & Curtis 1973; Porter 1988; Stokes & Bourne 1989; Schnulle and Hurley, 2003; Watson, 1980; Stirling et al., 2005
Tuboly et al, 1988; Harp and Moon, 1988; Kleinman and Walker, 1979; Salmon, 2000; Bourges et al, 2008; Wilson and Butcher, 2004
Immune component免疫成分
Location in the sow/ transfer to the MG母猪体内
部位/转移至乳腺
Transfer to the piglet/ location in the piglet转移至仔
猪/仔猪体内部位
Transfer to the MG转移至乳腺
Maternal cells are functional in the recipient: specific immunity
母体细胞对受体是功能性的：特定免疫§ Humans人: tuberculin sensitivity (DTH) transferred from mom to
offspring 结核菌素敏感性(DTH)从母亲转移到后代§ Schlesinger and Covelli 1977
§ Mice鼠: transfer of CMI sensitivity (DTH and lymphoproliferation) to nematode and fungal antigens CMI敏感度（DTH和淋巴组织增生）转移到线虫和真菌抗原
§ Rifkind§ Kumar
§ Pigs猪: ???
Maternally-derived antigen specific CMI is transferred to the neonate? 母体衍生的抗原特异性CMI被转移到新生儿？
母体猪肺炎支原体特异性细胞免疫被动转移至仔猪
A
DTH validation DTH验证
0
1
2
3
4
5
6
7
24 36 48
NonvaccinatedVaccinated
DxT
(mm
2 )
B
Time post injection (hours)
0
1
2
3
4
5
6
7
24 36 48
NonvaccinatedVaccinated
DxT
(mm
2 )
C
D
E
Negative Control 阴性对照: Saline 盐水
Positive Control 阳性对照: PHA
Experimental实验: M. hyopneumoniae肺炎支原体
PHA-DTH responses in piglets仔猪PHA-DTH反应
M. hyopneumoniae -DTH responses in piglets仔猪猪肺炎支原体DTH反应
M. hyopneumoniae specific immunity in piglets仔猪猪肺炎支原体特异性免疫
Time at piglet blood sampling仔猪采血时间
PS AS
S/P
ratio
Pre-suckling哺乳前 After-suckling哺乳后
M. hyopneumoniae-specific antibodies猪肺炎支原体特异性抗体
Pre-suckling哺乳前After-suckling哺乳后
M. hyopneumoniae-specific proliferation猪肺炎支原体特异性扩增
*
Variance: SE
M. h
yopn
eum
onai
e –
cont
rol (
%)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5V sowN sow
*
M. hyopneumoniae-immunity is transferred to piglets of vaccinated sows猪肺炎支原体免疫力转移给了免疫母猪的仔猪
猪肺炎支原体对照
S/P比值
DTH
lesi
on s
ize
(mm
)
M. hyopneumoniae DTH responses in 3 d-old pigs3日龄猪的猪肺炎支原体DTH反应
Maternal M. hyopneumoniae CMI is functional in the recipient母体肺炎支原体CMI对受体是功能性的
Conclusions 结论
Maternal M. hyopneumoniae immunity is transferred to piglets 母体肺炎支原体免疫力转移到仔猪
Maternal M. hyopneumoniae CMI participates in the neonatal immune response母体肺炎支原体CMI参与了新生猪的免疫反应
Vaccination of Neonates: pros and cons新生猪接种的利弊
Traditional dogma传统的教条: neonatal and functional immature and maternal immunity is immunosuppressive新生的，功能不成熟的和母体免疫是免疫抑制
Need to be revisited需要修订:
Vaccination of Neonates: Problems and Issues 新生猪接种疫苗：问题与建议Douglas Hodgins and Patricia Shewan Vaccine 30: 1541-59 2012
Obstacles to Neonatal vaccination新生猪接种疫苗的障碍
§ Corticosteriod associated with birth 与出生相关的皮质类固醇
§ Maternal cytokines eg TGF-b and IL-12 母体细胞激素，如TGF-b和IL-12 Nyugen et al 2007
§ Immunocompetent but Immunological Naïve 免疫功能正常，但免疫缺乏
§ No exposure to antigens 没有接触抗原
§ Complement low 补体低
§ Microflora 菌群
§ Colonization with normal flora-increase in IgG, IgA 定植正常菌群 - IgG，IgA增加-Butler et al 2000
§ Gnotobiotic pig with E.coli---T and T independent Ag 无菌猪给大肠杆菌 - T和T独立抗原
§ Germfree –No response 无菌- 无反应 Butler et al 2002
§ Adjuvant CpG enhanced response in gnotobiotic pigs CpG佐剂增强无菌猪的反应Butler et al 2005
Mucosal immune system黏膜免疫系统—Gut flora肠道菌群
§ Development of mucosal immune system in neonate driven by commensial microbial flora 微生物菌群驱动的新生猪黏膜免疫系统的发育 (Rothkotte etal 1991, Butler et al 2000)
§ Pathogen associated molecular patterns 病原相关分子模式 (eg MDP, LPS)§ Substitute for gut flora in driving immunosresponsiveness替代肠道菌群驱动免疫反应 (Butler
et al 2005)
Microflora will prove to be both essential for immune development and a approach in which to modulate responses微生物群落将被证明是免疫发育所必须，也是一种调节反应的方法
Pros of maternal immunity in the neonate新生猪母体免疫的优势
Cons of maternal immunity in the neonate新生猪母体免疫的劣势
• Contributes to the neonatal immune repertoire 有助于新生猪免疫保留
• Immediate immune protection 直接来源免疫保护
• Antigen neutralization & opsonization in vivo 抗原中和&体内调理作用
• Activate neonatal leukocytes 新生猪白细胞激活
• May allow for memory CMI responses in the neonate可以允许新生猪CMI反应记忆
• May allow for memory AMI responses in the neonate可以允许新生猪AMI反应记忆
• Masks B-cell epitopes掩盖B-细胞抗原决定基
• Potential interference with AMI responses AMI反应的潜在干扰
• Potential interference with CMI responsesCMI反应的潜在干扰
MDI (AMI) may not always beneficially affect development in the neonate
MDI（AMI）可能并不总是对新生猪的发育有有利影响
Sow Periphery母猪外周血 Mammary Gland (MG)
乳腺
Piglet仔猪
MDI influences neonatal immune developmentMDI影响新生儿免疫发育
• Pseudorabies伪狂犬病: •Wittan and Ohlinger, 1987
• Mycoplasma hyopneumoniae猪肺炎支原体: •Haesebrouk et al., 2006
• Swine influenza virus (SIV) 猪流感病毒•Loeffen et al., 2003
• Bordetella bronchiseptica支气管败血波氏杆菌: •Kono et al., 1994
• Classical swine fever (CSF) 猪瘟•Klinkenberg et al., 2002
• Pseudorabies 伪狂犬病•Bouma, 1998; Wittman and Ohlinger, 1987
• Measles 麻疹Gans, 2001
• BVDV Endsley, 2004
• Lymphocytic choriomeningitis virus淋巴细
胞性脉络丛脑膜炎病毒 Seiler, 1998
•Swine Influenza virus猪流感病毒• Classical Swine Fever猪瘟• Kitikoon et al., 2006; Surdahat and
Damrongwatanapokin, 2003
Sow vaccination 疫苗接种
Piglet vaccination and blood
collection仔猪接种疫苗和血液收集
DTH and blood collection DTH和采
血
DTH and blood collection DTH和采
血
Blood (0 & 24 hr) and colostrum collection血（24小时）和初乳采集
21 d14 d7 d0 d5 w 3 w
Commercial Farm: Prairie Land Pork in MN; not a naïve herd
Sow Vaccination status母猪接种情况
Vaccinated接种(10) Nonvaccinated未接种(10)
20 (V V) 20 (N V)
20 (V N) 20 (N N)
Piglet vaccination status仔猪疫苗接种
状态
Vaccinated接种 (V)
Nonvaccinated未接种 (N)
M. hyopneumoniae antibodies in piglets仔猪猪肺炎支原体抗体
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
14 21
S/P
rat
io
N N N V V V V N N N N V V V V N
14 day old piglets 14日龄仔猪, 7 dpv 21 day old piglets 21日龄仔猪, 14 dpv
Piglet Treatment仔猪处理Sow & Piglet treatment母猪及仔猪处理; N: Nonvaccinated未接种;
V: Vaccinated接种; dpv: days post vaccination接种后天数; Variance: SD方差
No evidence of AMI stimulation following piglet vaccination没有证据表明仔猪疫苗接种后AMI激活
S/P比值
M. hyopneumoniae-specific proliferation猪肺炎支原体特异性扩增
M. h
yopn
eum
onia
e –
cont
rol
猪肺
炎支
原体
-对照
(%)
0
2
4
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d14
a
14 day old piglets 14日龄仔猪, 7 dpv
N N N V V V V N -2
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d 21
b b
aa
N N N V V V V N
21 day old piglets 21日龄仔猪, 14 dpv
Piglet Treatment仔猪处理 Sow & Piglet treatment母猪及仔猪处理; N: Nonvaccinated 未接种; V: Vaccinated 接种; dpv: days post vaccination接种后天数; Variance: SE 标准误
Evidence of CMI stimulation following piglet vaccination仔猪疫苗接种后CMI激活的证据
0
2
4
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14
0 1 2 3 4 50
2
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0 1 2 3 4 5
N N N V V N V V N N N V V N V V
Piglet treatment 仔猪处理
21 day-old piglets 21日龄仔猪, 14dpv14 day-old piglets 14日龄仔猪, 7dpv
Sow & Piglet treatment母猪及仔猪处理; N: Nonvaccinated未接种; V: Vaccinated接种; dpv: days post vaccination接种后天数
Lesi
on s
ize 病灶大小
(mm
)
Evidence of CMI memory response following piglet vaccination 仔猪疫苗接种后CMI记忆反应的证据
Conclusions 结论7 day-old piglets respond to vaccination7日龄仔猪接种疫苗的反应
Maternally-derived cells are functional and participate in the antigen specific immune response in piglets 母体源性细胞是功能性的，并参与仔猪抗原特异性免疫反应
No evidence that passively transferred immunity interferes with CMI responses in piglets 没有证据表明被动转移免疫力干扰仔猪CMI反应
Transfer of maternally-derived immunity (MDI) from colostrum to the piglet自初乳将母源免疫力转移至仔猪
Sow Periphery母猪外周
Mammary Gland (MG)乳腺
Piglet仔猪
Effects of management Cross fostering? 管理交叉寄养的效应?
The effect of cross-fostering on transfer of maternal Mycoplamsa
hyopneumonia-specific immune transfer交叉寄养对母源猪肺炎支原体特异性免疫
转移的影响Bandrick et al Vet Record 2011
5 weeks 3 weeks 0h 6h 12h 18h 24h 36h 48h 72h
piglet movement仔猪移动
piglet movement仔猪移动
piglet movement仔猪移动
piglet movement仔猪移动
AS blood collection哺乳后采血
DTH sample
injectionDTH样品注入
DTH measurement
DTH测量
PS blood collection哺乳前采血
Piglet age (hrs) 仔猪年龄（小时）
Endpoints终点:Sows母猪: Serum-Antibody quantitation via ELISA通过ELISA血清抗体定量Piglets仔猪:
Delayed-type hypersensitivity (DTH) 迟发型超敏反应Serum-Antibody quantitation via ELISA通过ELISA血清抗体定量
Sow vaccination母猪疫苗接
种
Sow blood collection母
猪采血
***
S:P
ratio
Pre-vaccination接种前 Nonvaccinated未接种 Vaccinated接种
Sow M. hyopneumoniae vaccination status母猪猪肺炎支原体疫苗接种状态
Figure 2A. Mycoplasma hyopneumoniae-specific antibodies in sow serum 图2A. 母猪血清中猪肺炎支原体特异性抗体
0.0
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***
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3.5
***
S:P
ratio
S：P比
Nonvaccinated未接种 Vaccinated接种
Sow M. hyopneumoniae vaccination status 母猪猪肺炎支原体疫苗接种状态
Figure 2B. Mycoplasma hyopneumoniae-specific antibodies in sow colostrum 图2B. 母猪初乳中的猪肺炎支原体特异性抗体
Figure 2. Mycoplasma hyopneumoniae-specific antibodies in sows 图2. 母猪猪肺炎支原体特异性抗体
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Non-cross-fostered 非交叉培育
Vaccinated NonvaccinatedDam vaccination status Dam疫苗接种状况
Vaccinated接种 x Nonvaccinated未接种
Time at cross-fostering交叉寄养时间
0 6 12 20
Vaccinated接种 x Vaccinated接种
Time at cross-fostering交叉寄养时间
0 6 12 20
Nonvaccinated未接种 x Vaccinated接种
Time at cross-fostering交叉寄养时间
0 6 12 20
DTH
orth
ogon
al d
iam
eter
DTH
正交
外径
(mm
)D
TH o
rthog
onal
dia
met
erD
TH正
交外
径 (m
m)
DTH
orth
ogon
al d
iam
eter
DTH
正交
外径
(mm
)D
TH o
rthog
onal
dia
met
erD
TH正
交外
径 (m
m)
A B
C D
Figure 3. Mycoplasma hyopneumoniae-specific DTH responses in piglets at 3 d of age图3. 猪肺炎支原体特异性DTH反应，仔猪3日龄
a
b
b b
a a
a a
b b
0.0
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0 1 2 30.0
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0 6 12 20
Non-cross-fostered非交叉培育
Vaccinated接种 Nonvaccinated未接种
Dam vaccination statusDam疫苗接种状况
Vaccinated接种x Nonvaccinated未接种
Time at cross-fostering交叉寄养时间
0 6 12 20
Vaccinated接种x Vaccinated接种
Time at cross-fostering交叉寄养时间
0 6 12 20
Nonvaccinated未接种x Vaccinated接种
Time at cross-fostering交叉寄养时间
0 6 12 20
S:P
ratio
S：P比
S:P
ratio
S：P比
S:P
ratio
S：P比
S:P
ratio
S：P比
A B
C D
Figure 4. Mycoplasma hyopneumoniae-specific antibodies in piglets at 24 hrs of age图4. 猪肺炎支原体特异性抗体, 仔猪24小时龄
a
b a
b bb
b
cd
a
Conclusions 结论
Cross-fostering affects transfer of maternally-derived CMI and AMI differently交叉寄养不同地影响母源性CMI和AMI传递
Sow immune status should be uniform母猪免疫状态应该是一致的
Cross-foster pigs after 12 at least 12 hours 至少12小时后交叉寄养猪
Amazing Immune system in Neonatal pig Summary惊人的新生猪免疫系统总结
§ Swine are different in their immune system and response compared to humans and mice. 猪与人和鼠相比免疫系统和反应是不同的
§ Both AMI and CMI is transferred to piglets in colostrum; there is selectivity in lymphocyte transfer AMI和CMI都通过初乳被转移至仔猪，淋巴转移有选择性
§ Maternally-derived CMI is functional in the recipient母源性CMI对受体是功能性的
§ Piglets respond to vaccination with CMI responses in the face of MDI面对MDI，仔猪以CMI反应来回应疫苗接种
§ No evidence of passive interference with CMI responses from MDI at least in M. hyopneunominae至少在猪支原体肺炎没有来自MDI的CMI反应被动干预的证据
Amazing Immune system summary cont…惊人的免疫系统总结续
§ Important consideration重要的考虑因素 Vaccination programs疫苗接种计划
Pay attention to maternally-derived CMI注意母体源性CMI
CMI is an important response and may be stimulated even when there is a lack in AMI responses CMI是一个重要的反应，且可能在AMI反应缺乏时被激活
Cross-fostering timing and piglet management 交叉寄养时间和仔猪管理
§ Question问题: Using this information--what are the further challenges and opportunities?
§ 使用此信息进一步的挑战和机遇是什么？
Acknowlegement致谢
§ University of Minnesota Collaborators明尼苏达大学的合作者
Meggan Bandrick DVM PhDGamal Elmubark MD PhDMike Olin PhDSam Baidoo, PhDMike Murtaugh PhD
• Funding support资金支持
Minnesota Pork BoardNational Pork BoardNIH T32 (Bandrick)Zoetis
Future directions未来的发展方向--Wellness Testing健康测试
§ Acute Phase proteins急性时相蛋白
§ Immunoglobulins免疫球蛋白
General, Ag specific总体的，抗原特异的
§ Immune cell population-免疫细胞群
numbers, function数字，功能
§ Cell mediated responses细胞介导的反应
ELISPOT , general, Ag-specific酶联免疫斑点，总体的，抗原特异的
§ Cytokine measures 细胞因子测量
