宿主防御區(qū)段-第五neruo-immuno enrine network

NeuroimmunoRegulation&

Neuro-immuno-endocrineNetworkHaixiaLuMD,PhDInstituteofNeurobiology,SchoolofBiomedicalSciencesE-mail:Tel:1.Neuroimmunology*;2.Interactionbetweennervoussystemandimmunesystem*;3.Immune-braincommunication4.Immune-endocrinecommunication5.Neuro-immuno-endocrinenetwork*Outline:References:1.壽天德主編《神經(jīng)生物學(xué)》，第2版，高等教育出版社2.李云慶主編《神經(jīng)科學(xué)基礎(chǔ)》，第2版，高等教育出版社3.Wikipedia

（維基百科）4.ChesnokovaVandMelmedS.Minireview:Neuro-Immuno-EndocrineModulationoftheHypothalamic-Pituitary-Adrenal(HPA)Axisbygp130SignalingMolecules.Endocrinology.2002,143(5):1571–15745.ChaczkoZandMosesP.Neuro-Immune-Endocrine(NIE)ModelsforEmergencyServicesInteroperatibility.LectureNotesinComputerScience.2007,4739:105-1126.KaiserP,WuaZ,RothwellL,etal.Prospectsforunderstandingimmune-endocrineinteractionsinthechicken.GeneralandComparativeEndocrinology.2009,163:83–917.胡格，穆祥，段慧琴，楊佐君，高立云.免疫、神經(jīng)和內(nèi)分泌系統(tǒng)間的關(guān)系.動(dòng)物醫(yī)學(xué)進(jìn)展，2003，24(1)：5-7NervoussystemEndocrinesystemNeuralinnervationNeurotransmittersNeuropeptidesHormonesInteractionbetweenNervesystemandEndocrinesystem（復(fù)習(xí)“神經(jīng)內(nèi)分泌調(diào)節(jié)”內(nèi)容）Driveorinhibition

oftenstartsintheCNS.NegativeorPositiveFeedbackfromperipheralhormonestomaintainlevelsatasetpoint.I.ConceptofNeuroimmunologyStudyofinteractionsbetweentheimmuneandthenervoussystemsArapidlygrowingareaofresearchwithenormouspotentialtocontributetoourunderstandingofphysiologicalanddiseaseprocessesNeuralImmunoregulationNeuroimmunoRegulationImmuneresponsetodiseasesofthenervesystemInfectivediseaseAutoimmunediseaseIschemicdiseaseDegenerativediseaseTraumaticdiseaseNeoplasm(新生物，腫瘤)II.ClassicalfieldsofNeuroimmunology抵抗力排斥反應(yīng)III.InteractionbetweenNervoussystemandImmunesystemNointeraction!Thecentralnervoussystemwasconsideredasanimmunologicalprivileged(免疫豁免)siteImmuneresponse1.Bloodbrainbarrier(BBB)-circulatingbloodandthebrainextracellularfluid(BECF)血-腦、血-腦脊液和腦脊液-腦三種屏障的總稱2.Pro-apoptoticmolecules(促凋亡因子)

atBBB3.NoMHC(majorpatibilitycomplex)moleculesonnervecells(神經(jīng)細(xì)胞沒有主要組織相容性復(fù)合體)4.Noclassicaldendriticcells(樹突狀細(xì)胞)intheCNS1.Bloodbrainbarrier(BBB)-circulatingbloodandthebrainextracellularfluid(BECF)However1.ExistenceoflymphdrainageintheCNS(淋巴引流)2.PassageofTandBcellsthroughBBB(hypothalamus)(T,B細(xì)胞可以通過BBB)3.Microgliacanprocessandpresentantigens(小膠質(zhì)細(xì)胞)III.InteractionbetweenNervoussystemandImmunesystemSoTheinteractiondoesexist.NeuralinfluencesontheimmunesystemModulationofnervecellfunctionbyimmuneandinflammatorymediatorsSimilaritiesbetweennerveandimmunecellsIII.InteractionbetweenNervoussystemandImmunesystemAgrin:heparansulphateproteoglycan,stabilizessynapsis;rapsyn,inducesclusteringofAchreceptor;EphrinB:receprtortyrosinekinase;NMDAR:N-methyl-D-aspartatereceptor,glutamatereceptor;PSD95:postsynapticdensityprotein95requiredforsynapticplasticity;CD2AP:CD2adaptorprotein,adapterproteinbetweenmembraneproteinsandtheactincytoskeletonNeuralinfluencesontheimmunesystem1.Whatarethestructuresthatareinvolvedinneuroimmunoregulation?Centralnervoussystem(CNS):

Hypothalamus,Pituitary,SpinalcordPeripheralnervoussystem(PNS):

Nerve,Sensoryreceptors,Ganglia,etcNervecells:

Neurons,Glia(Astrocytes,Microglia,etc)III.InteractionbetweenNervoussystemandImmunesystemMicrogliaMicrogliaareatypeofglialcellthataretheresidentmacrophagesofthebrainandspinalcord,andthusactasthefirstandmainformofactiveimmunedefenseinCNS.MicrogliaPartofmononuclearphagocytesystemExpresstypicalmonocytemarkerslikeCD11b,CD45,MHCIIUniqueisabilitytoproliferateDifferentiateuponactivationLongsurvival(over6months)FriendofneuronsPhagocytoseapoptoticneuronsSecreteneuroprotectivefactors(BDNF,NT-3)RestingmicrogliasecreteIL-10Foe

(敵人)ofneuronsSecreteneurotoxicmoleculesTNFandIL-1,glutamate,freeradicalspeciesCaninduceapoptosisInteractwithastrocytesAstrocyte-MicrogliaInteractionNeuralinfluencesontheimmunesystem2.CommunicationBetweenNerveSystemandImmuneSystem*III.InteractionbetweenNervoussystemandImmunesystem2.1Innervation2.2Communicationthroughneutrotransmittersandneuropeptides-Immunecellsexpressthereceptorsofneuralproducts2.3CytokinesproducedbyNervecellsNeuralinfluencesontheimmunesystem2.1Innervationthymus,spleen,lymphnodesSympatheticnerves:

來自頸胸段交感神經(jīng)鏈

Parasympatheticnerves:

來自迷走神經(jīng)

Peptidergicnerves：如SP、VIP、NPY、CGRP等肽能神經(jīng)纖維

Cholinergicanti-inflammatorypathway(膽堿能抗炎通路)III.InteractionbetweenNervoussystemandImmunesystem2.CommunicationBetweenNerveSystemandImmuneSystem*Neuralinfluencesontheimmunesystem2.2Communicationthroughneutrotransmittersandneuropeptides-ImmunecellsexpressthereceptorsofneuralproductsAcetylcholine:增加淋巴細(xì)胞和巨噬細(xì)胞的數(shù)量，促進(jìn)其產(chǎn)生IL

Monoamines(一元胺)Norepinephrine(NE)：抑制干擾素的作用

Dopamine(多巴胺)：刺激免疫反應(yīng)

Serotonine(5-HT)：抑制體液免疫，B細(xì)胞分泌Ig能力下降

Histamine(組胺)：抑制巨噬細(xì)胞的功能，減少干擾素以及IL-2的產(chǎn)生III.InteractionbetweenNervoussystemandImmunesystem2.CommunicationBetweenNerveSystemandImmuneSystem*NeuralinfluencesontheimmunesystemAcetylcholine:增加淋巴細(xì)胞和巨噬細(xì)胞的數(shù)量，促進(jìn)其產(chǎn)生IL

Monoamines(一元胺)：

Neuropeptides

Endorphines(內(nèi)啡肽)：刺激免疫反應(yīng)，也有相反報(bào)道

SubstanceP(P-物質(zhì))：刺激免疫反應(yīng)

VasoactiveIntestinalPeptide(血管活性腸肽)：抑制免疫反應(yīng)

Enkephaline(腦啡肽)：刺激免疫反應(yīng)為主III.InteractionbetweenNervoussystemandImmunesystem2.2Communicationthroughneutrotransmittersandneuropeptides-Immunecellsexpressthereceptorsofneuralproducts2.CommunicationBetweenNerveSystemandImmuneSystem*NeuralinfluencesontheimmunesystemAcetylcholine:增加淋巴細(xì)胞和巨噬細(xì)胞的數(shù)量，促進(jìn)其產(chǎn)生ILMonoamines(一元胺)：

Neuropeptides

Others：GABA,Glycine（氨基乙酸）,Glutamate,NitricoxideIII.InteractionbetweenNervoussystemandImmunesystem2.2Communicationthroughneutrotransmittersandneuropeptides-Immunecellsexpressthereceptorsofneuralproducts2.CommunicationBetweenNerveSystemandImmuneSystem*Neuralinfluencesontheimmunesystem2.3CytokinesproducedbyNervecellsGlialcellssecretILs,TNF,IFN,etc-Astrocytes:IFN,TNF-Microglia:IL-10,IL-1,TNFIII.InteractionbetweenNervoussystemandImmunesystem2.CommunicationBetweenNerveSystemandImmuneSystem*NeuralinfluencesontheimmunesystemInnervation:

SympatheticnervesandparasympatheticnervesNeurotransmitters:

acetylcholine,norepinephrine,serotonin,etcNeuropeptides:

SubstanceP,endorphin,etcCytokines:IL,IFN,TNFIII.InteractionbetweenNervoussystemandImmunesystemModulationofnervecellfunctionbyimmuneandinflammatorymediatorsIII.InteractionbetweenNervoussystemandImmunesystemModulationofnervecellfunctionbyimmuneandinflammatorymediators1.Evidencesofimmunemodulationofnervecells

Nervecellsexpressreceptorsofimmunoregulators

神經(jīng)細(xì)胞表達(dá)免疫調(diào)質(zhì)的受體III.InteractionbetweenNervoussystemandImmunesystem

Passageofimmunoregulator(IL-1)throughBBB

免疫調(diào)質(zhì)（白細(xì)胞介素-1）通過血腦屏障

Neurotransmittersandneuropeptidesproducedbyimmunecells

免疫細(xì)胞可產(chǎn)生神經(jīng)遞質(zhì)和神經(jīng)肽

PassageofTandBcellsthroughBBB

免疫細(xì)胞通過血腦屏障NGFandNT-ssecretedbyTlymphcellsBraincellsexpressreceptorsforimmuneproductsModulationofnervecellfunctionbyimmuneandinflammatorymediators2.Immunemodulationofnervecells-8aspects2.4Modulatingthesynthesisandreleasingofneurotransmittersandneuropeptides調(diào)節(jié)神經(jīng)遞質(zhì)、神經(jīng)肽的產(chǎn)生和釋放2.3Affectingthefunctionofvegetativenerve(automaticsystem)

影響植物神經(jīng)功能如：IL-1andINFstimulatethefoodintakeandinducefever

2.1Effectsonnervecellproliferationanddifferentiation

影響神經(jīng)細(xì)胞生長(zhǎng)、分化如：IL-6促進(jìn)PC12分化為神經(jīng)元，促使星形膠質(zhì)細(xì)胞分泌NGFIII.InteractionbetweenNervoussystemandImmunesystem2.2Neuroprotectionandneurotoxicity神經(jīng)保護(hù)和神經(jīng)毒性如：TNF引起少突膠質(zhì)細(xì)胞死亡以及脫髓鞘,IL-6抑制NMDA毒性Modulationofnervecellfunctionbyimmuneandinflammatorymediators2.Immunemodulationofnervecells-8aspects2.6EffectsonAnalgesia參與鎮(zhèn)痛如：INF通過影響中樞阿片類物質(zhì)的功能而參與鎮(zhèn)痛

2.7Inducingandmediatinggeneexpression刺激和介導(dǎo)基因表達(dá)

如：血小板激活因子PAF誘導(dǎo)神經(jīng)元的基因表達(dá)2.8Effectonhighbrainfunction(memoryandlearning)

影響腦的高級(jí)功能如：IL-6，IL-1，TNF等抑制LTP，使記憶力下降III.InteractionbetweenNervoussystemandImmunesystem2.5Adjustingnervecellactivity調(diào)節(jié)神經(jīng)細(xì)胞的活動(dòng)狀態(tài)

IL-2,TNF,IL-6,IFNNatureReviewsImmunologyISSN:1474-1733EISSN:1474-1741Cytokinehypothalamic-pituitary-adrenalaxis

iii).Influencesonimmunefunctionthroughneurotransmittersorneuropeptidesii).Neuralcellsproduce/release

immuneregulatorsi).InnervationofimmunesystemNervecellproliferationanddifferentiationNeuralprotectionandneuraltoxicityNervecellactivityNervecellfunction-transmitters,peptidesNeuralfunction-automaticsystemHighbrainfunctionOtherfunction-AnalgesiaGeneexpression-mechanismIII.InteractionbetweenNervoussystemandImmunesystemNeuralinfluencesontheimmunesystem

Innervation:Neurotransmitters:

acetylcholine,norepinephrine,serotonin,etcNeuropeptides:

SubstanceP,endorphin,etcCytokines:

IL,IFNTNFModulationofnervecellfunctionbyimmuneandinflammatorymediatorsCytokinesReactiveoxygenandnitrogenspecies(活性氧、活性氮)III.InteractionbetweenNervoussystemandImmunesystemIV.InteractionbetweenEndocrinesystemandImmunesystemInfluenceofimmuneregulatorsonneuroendocrineEvidenceofinteractionbetweenendocrinesystemandimmunesystemImmunecellsexpressthereceptorofneurohormoneNeurohormonereceptorsarefoundoninmunecells:

corticortrophin-releasingfactorgrowthhormoneadrenocorticotrophinhormoneprolactinIV.InteractionbetweenEndocrinesystemandImmunesystem2.InteractionpathwaysCytokineHPAaxisInfluenceofimmuneregulatorsonneuroendocrineCytokineHypothalamusPituitaryglandAdrenalglandCRHACTHGlucocorticoidImmunesystemIL1,IL2,IL6,IL11,IL12,TNFa,INFgNatureReviewsImmunologyISSN:1474-1733EISSN:1474-1741Cytokinehypothalamic-pituitary-adrenalaxis

IV.InteractionbetweenEndocrinesystemandImmunesystem2.InteractionpathwaysCytokine-HPAaxis*Cytokine-HPGaxisInfluenceofimmuneregulatorsonneuroendocrineIV.InteractionbetweenEndocrinesystemandImmunesystem2.InteractionpathwaysCytokine-HPAaxis*Cytokine-HPGaxisPituitary-thymusaxisthymosin

α1,thymulininducethereleasingofACTH,LHandLHRHGHandPRLinducethedevelopmentofthymusInfluenceofimmuneregulatorsonneuroendocrineIV.InteractionbetweenEndocrinesystemandImmunesystem2.InteractionpathwaysCytokine-HPAaxis*Cytokine-HPGaxisPituitary-thymusaxisHormonecanbesynthesizedandreleasedfromimmunecellsthymusproduceGH,PRLLymphcellsproduceTSH,ACTHInfluenceofimmuneregulatorsonneuroendocrineIV.InteractionbetweenEndocrinesystemandImmunesystem1.GlucocorticoidssuppressimmunereactionGlucocorticoidsuppressesthesynthesisofIL-1,IL-2Glucocorticoidsuppressesthereleasingoflymphokines(淋巴因子)GlucocorticoidinducesthymuscelldeathLymphokinesareasubsetofcytokinesthatareproducedbyTcellstodirecttheimmunesystemresponse.LymphokinesaidBcellstoproduceantibodies.Itisnotantibodyorantigen.-FromWikipediaModulationofimmunesystembyendocrinesystemIV.InteractionbetweenEndocrinesystemandImmunesystem2.SynthesizeofimmuneregulatorsbyendocrinecellsIL-6frompituitaryglandIL-1fromadrenalglandNotmanyreportsbasedonthistopicModulationofimmunesystembyendocrinesystemIV.InteractionbetweenEndocrinesystemandImmunesystemModulationofimmunesystembyendocrinesystem3.Feedbackbetweenmelatonin(MLT,褪黑素)andcytokinesMLTup-regulatesthereleasingofIL-2fromlymphcellanddendriticcell,whileIL-2reducesthereleasingofMLTTNFincreasesthereleasingofMLT,howeverMLTinhibitsthethesynthesis