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TheThe ImmuneImmune SystemSystem

Xue Hui

DepartmentDepartment ofof HistologyHistology && EmbryologyEmbryology IntroductionIntroduction

ˆˆ ComponentsComponents

ˆˆ FunctionFunction ˆˆ MechanismsMechanisms ofof ImmunityImmunity StructuralStructural componentscomponents ofof thethe immuneimmune systemsystem

ˆ Immune cell „ „ presenting cell „ „ ˆ Immune tissue ( Lymphatic tissue ) „ Diffuse lymphoid tissue „ Lymphoid nodule ˆ Immune organ ( Lymphatic organ ) „ Central lymphoid organ „ Peripheral lymphoid organ

LymphocyteLymphocyte

ˆ SmallSmall lymphocytelymphocyte „„ Diameter:Diameter: 66 ~~ 88μμmm ˆ MediumMedium -- sizedsized lymphocytelymphocyte „„ Diameter:Diameter: 99 ~~ 1212μμmm ˆ LargeLarge lymphlymphocyteocyte „„ Diameter:Diameter: 1313 ~~ 2020μμmm LymphocyteLymphocyte

Medium - sized lymphocyte (Left) & Small lymphocyte (Right) LymphocyteLymphocyte LymphocyteLymphocyte

ˆˆ ThymusThymus dependentdependent lymphocytelymphocyte (T()cell) „„ HelperHelper cellcell (Th(Th cell)cell) „„ CytotoxicCytotoxic cellcell (Tc(Tc cell)cell) „„ MemoryMemory cellcell ˆˆ BoneBone marrowmarrow dependentdependent lymphocytelymphocyte (B()cell) ˆˆ NaturalNatural killerkiller cellcell (NK(NK cell)cell) LymphocyteLymphocyte

T Cell

NK Cell

B Cell StructuralStructural ComponentsComponents ofof thethe immuneimmune systemsystem

ˆ Immune cell „ Lymphocyte „ Antigen presenting cell (APC) „ Plasma cell „ Granulocyte ˆ Immune tissue ( Lymphatic tissue ) „ Diffuse lymphoid tissue „ Lymphoid nodule ˆ Immune organ ( Lymphatic organ ) „ Central lymphoid organ „ Peripheral lymphoid organ LymphaticLymphatic tissuetissue

ˆˆ DiffuseDiffuse lymphaticlymphatic tissuetissue „ Postcapillary venule ˆˆ LymphaticLymphatic nodulenodule „„ PrimaryPrimary lymphoidlymphoid nodulenodule „„ SecondarySecondary lymphoidlymphoid nodulenodule ˆˆGerminalGerminal centercenter DiffuseDiffuse lymphoidlymphoid tissuetissue && LymphoidLymphoid nodulenodule Postcapillary venule LymphoidLymphoid nodulenodule

↓: Afferent lymphatic vessels ※ : Subcapsular sinus D : Dark zone L : Light zone C : Cap LymphaticLymphatic organorgan

ˆˆ CentralCentral lymphaticlymphatic organorgan „„ ThymusThymus „„ BoneBone marrowmarrow ˆˆ PeripheralPeripheral lymphaticlymphatic organorgan „„ LymphLymph nodenode „„ SpleenSpleen „„ TonsilTonsil ThymusThymus

ˆˆ StructureStructure ofof thethe thymusthymus „„ CapsuleCapsule ˆˆ InterlobularInterlobular septumseptum „„ ParenchymaParenchyma ˆˆ ThymicThymic lobulelobule „„ CortexCortex ------DarkDark stainingstaining „„ MedullaMedulla ------LightLight stainingstaining ThymusThymus

★★ △△

Capsule △Cortex ★Medulla ThymusThymus

ˆˆ StructureStructure ofof thethe thymusthymus „„ ReticularReticular connectiveconnective tissuetissue „„ EpithelialEpithelial reticularreticular cellcell ThymusThymus cortexcortex

ˆˆ ThymusThymus epithelialepithelial cellcell (epithelial(epithelial reticularreticular cell)cell) „„ SubcapsularSubcapsular epithelialepithelial cellcell ˆˆ NurseNurse cellcell „„ InterdigitatingInterdigitating dendriticdendritic cellcell ˆˆ ThymocyteThymocyte ˆˆ ThymusThymus matrixmatrix cellcell ThymusThymus Subcapsular epithelial cell Interlobular septum Nurse cell

Thymocyte Cortex Interdigitating

Macrophage Interdigitating dendritic cell

Medulla Medullary epithelial cell

Thymic corpuscle epithelial cell Thymus

E: Epithelial reticular cell

T: ThymusThymus medullamedulla

ˆˆ ThymusThymus epithelialepithelial cellcell „„ MedullaryMedullary epithelialepithelial cellcell „„ ThymicThymic corpusclecorpuscle epithelialepithelial cellcell ˆˆ ThymicThymic corpusclecorpuscle (( oror HassallHassall’’ss corpusclecorpuscle )) ˆˆ MatureMature thymocytethymocyte ˆˆ MacrophageMacrophage ThymusThymus Subcapsular epithelial cell Interlobular septum Nurse cell

Thymocyte Cortex Interdigitating dendritic cell

Macrophage Interdigitating dendritic cell

Medulla Medullary epithelial cell

Thymic corpuscle epithelial cell Thymus medulla Thymic corpuscle

H: Thymic corpuscle or Hassall corpuscle BloodBlood –– thymusthymus barrierbarrier

ˆˆ EndotheliumEndothelium ofof continuouscontinuous capillarycapillary ˆˆ BasementBasement membranemembrane aroundaround endotheliumendothelium ˆˆ PeriPeri--vesselvessel spacespace aroundaround capillarycapillary ,, whichwhich containscontains macrophagesmacrophages ˆˆ BasementBasement membranemembrane ofof epithelialepithelial reticularreticular cellscells ˆˆ ProcessesProcesses ofof epithelialepithelial reticularreticular cellscells BloodBlood –– thymusthymus barrierbarrier

Processes of epithelial reticular cells

Cell junction Basement membrane of epithelial reticular cells Endothelium of continuous capillary Basement membrane around endothelium Peri-vessel space Macrophage

Lymphocyte BloodBlood –– thymusthymus barrierbarrier FunctionFunction ofof thethe thymusthymus

ˆˆ TheThe thymusthymus isis thethe sitesite ofof thethe terminalterminal differentiationdifferentiation andand selectionselection ofof TT .lymphocytes. ˆˆ TheThe thymusthymus produceproduce severalseveral proteinsproteins thatthat actact asas growthgrowth factorsfactors toto stimulatestimulate proliferationproliferation andand differentiationdifferentiation ofof TT lymphocytes.lymphocytes. LymphoidLymphoid organorgan

ˆˆ CentralCentral lymphoidlymphoid organorgan „„ ThymusThymus „„ BoneBone marrowmarrow ˆˆ PeripheralPeripheral lymphoidlymphoid organorgan „„ LymphLymph nodenode „„ SpleenSpleen „„ TonsilTonsil Lymph node ParenchymaParenchyma ofof thethe lymphlymph nodenode

ˆ CortexCortex „„ SuperfacialSuperfacial cortexcortex ˆˆ LymphoidLymphoid nodulenodule ˆˆ DiffuseDiffuse lymphoidlymphoid tissuetissue „„ ParacortexParacortex zonezone (Deep(Deep cortexcortex unit)unit) „ Postcapillary venule „„ CorticalCortical sinussinus ˆˆ SubcapsularSubcapsular sinussinus ˆˆ PeritrabecularPeritrabecular sinussinus ˆ MedullaMedulla „„ MedullaryMedullary cordcord „„ MedullaryMedullary sinussinus SuperfacialSuperfacial cortexcortex andand deepdeep cortexcortex unitunit ofof lymphlymph nodenode

Afferent lymphatic vessel

Lymphoid nodule

Deep cortex unit (Central zone) Deep cortex unit (Peripheral zone)

Medulla Lymph node SuperfacialSuperfacial cortexcortex ofof thethe lymphoidlymphoid nodulenodule

↓: Afferent lymphatic vessels ※ : Subcapsular sinus D : Dark zone L : Light zone C : Cap Cortex of the lymph node Paracortex zone of the lymph node

Postcapillary venule Postcapillary venule in the lymph node

Reticular cell

High endothelial cell Lymphocyte

Lymphocyte

Lymphocyte

Nuclear of endothelial cell

Lymphocyte Postcapillary venule in the lymph node

Postcapillary venule lymphocyte Postcapillary venule in the lymph node

Postcapillary venule lymphocyte Cortex of the lymph node Subcapsular sinus of the lymph node

Afferent lymphatic vessel Endothelial cell Valve Capsule

Endothelial cell

Lymphocyte Astroid Macrophage Endothelial cell

Endothelial cell

Reticular cell Lymphocyte Macrophage Subcapsular sinus of the lymph node Medulla of the lymph node

Medullary cord Medullary sinus Trabecula LymphLymph circulationcirculation inin thethe lymphlymph nodenode LymphLymph circulationcirculation inin lymphlymph nodenode

Afferent lymphatic vessels

Subcapsular sinus Peritrabecular sinus

Cortex lymphoid tissue

Medullary sinus

Efferent lymphatic vessels FunctionFunction ofof thethe lymphlymph nodenode

ˆˆ FilterFilter lymphoidlymphoid fluidfluid ˆˆ ParticipateParticipate inin immuneimmune responseresponse ˆˆ ParticipateParticipate inin recirculationrecirculation ofof lymphocyteslymphocytes RecirculationRecirculation ofof lymphocyteslymphocytes

Afferent lymphatic vessel Postcapillary venule

Germinal center

Medullary sinus Lymphocytes in Arteriole Efferent artery system lymphatic vessel LymphoidLymphoid organorgan

ˆˆ CentralCentral lymphoidlymphoid organorgan „„ ThymusThymus „„ BoneBone marrowmarrow ˆˆ PeripheralPeripheral lymphoidlymphoid organorgan „„ LymphLymph nodenode „„ SpleenSpleen „„ TonsilTonsil SpleenSpleen

ˆˆ StructureStructure ofof thethe spleenspleen

ˆˆ BloodBlood circulationcirculation ofof thethe spleenspleen

ˆˆ FunctionFunction ofof thethe spleenspleen StructureStructure ofof thethe spleenspleen

ˆˆ CapsuleCapsule && trabeculatrabecula ˆˆ ParenchymaParenchyma „„ WhiteWhite pulppulp ˆˆ PeriarterialPeriarterial lymphaticlymphatic sheathsheath ˆˆ SplenicSplenic corpusclecorpuscle „„ MarginalMarginal zonezone „„ RedRed pulppulp ˆˆ SplenicSplenic cordcord ˆˆ SplenicSplenic sinusoidsinusoid SpleenSpleen

Trabecula White Red pulp StructureStructure ofof thethe spleenspleen

S: Splenic sinus SplenicSplenic corpusclecorpuscle

Germinative center

Central artery RedRed pulppulp ofof thethe spleenspleen RedRed pulppulp ofof thethe spleenspleen

Splenic cord Splenic sinusoid RedRed pulppulp ofof thethe spleenspleen RedRed pulppulp ofof thethe spleenspleen

M: Macrophage SplenicSplenic sinusoidsinusoid

M: Macrophage SplenicSplenic sinusoidsinusoid

1. Endothelial cell 2. Red cell 3. Lymphocyte 4. Macrophage 5. Granulocyte 6. Reticular cell SpleenSpleen

ˆˆ StructureStructure ofof thethe spleenspleen ˆˆ BloodBlood circulationcirculation ofof thethe spleenspleen ˆˆ FunctionFunction ofof thethe spleenspleen BloodBlood circulationcirculation ofof thethe spleenspleen

S: Splenic sinus BloodBlood circulationcirculation ofof thethe spleenspleen

Splenic arteries

Trabecular arteries Central arteries

Marginal zone sinuses Penicillar arteriole

Splenic cord Splenic sinus

Pulp venules

Splenic vein Trabecula vein SpleenSpleen

ˆˆ StructureStructure ofof thethe spleenspleen

ˆˆ BloodBlood circulationcirculation ofof thethe spleenspleen

ˆˆ FunctionFunction ofof thethe spleenspleen FunctionFunction ofof thethe spleenspleen

ˆˆ BloodBlood filterfilter ˆˆ ImmunologicalImmunological defencedefence ˆˆ ProductionProduction ofof bloodblood cellscells ˆˆ BloodBlood storagestorage MononuclearMononuclear phagocyticphagocytic system,system, MPSMPS

ˆˆ Definition:Definition: monocytesmonocytes andand macrophagesmacrophages ˆˆ ConstitutorConstitutor „„ LiverLiver::KupfferKupffer cellcell „„ LungLung::DustDust cellcell „„ NerveNerve tissuetissue::MicrogliaMicroglia „„ OsseousOsseous tissuetissue::OsteoclastOsteoclast „„ SkinSkin::LangerhansLangerhans cellcell ˆˆ Function:Function: phagocytosephagocytose SummarySummary

ˆ MasterMaster thethe classificationclassification andand functionsfunctions ofof lymphocytelymphocyte .. ˆ UnderstandUnderstand mononuclearmononuclear phagocyticphagocytic system.system. ˆ MasterMaster mainmain structurestructure andand functionsfunctions ofof thymus,thymus, lymphlymph nodenode andand .spleen. ˆ UnderstandUnderstand thethe compositioncomposition andand mainmain functionsfunctions ofof immuneimmune system.system. ˆ UnderstandUnderstand thethe structurestructure andand functionsfunctions ofof diffusediffuse lymphoidlymphoid tissuetissue andand lymphoidlymphoid nodulesnodules