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Lymphoid Organs

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LLymphatc

ymphatc Sysem

Sysem

 Lymphatc vessels  Lymphatc vessels  1ºlymphoid organs  1ºlymphoid organs  Thymus  Thymus  Bone marrow  Bone marrow  2ºlymphoid organs  2ºlymphoid organs  Lymph nodes  Lymph nodes  Adenoids  Adenoids  Tonsils  Tonsils  Spleen  Spleen  Appendix  Appendix  SALT  SALT  ALT  ALT  BALT  BALT

(2)

A! "unctons A! "unctons

1! #emove excess inersttal $uid 1! #emove excess inersttal $uid 2! Transpor o% dieary lipids

2! Transpor o% dieary lipids

&! Speci'c immuniy (as compared o non)speci'c immuniy* &! Speci'c immuniy (as compared o non)speci'c immuniy*

Lymph organs and tssues Lymph organs and tssues

•+rimary (re,uired %or sem +rimary (re,uired %or sem cell immunocompeance*cell immunocompeance*

i! red marrow produces all lymphoid precursor cells -u also .educaes. i! red marrow produces all lymphoid precursor cells -u also .educaes. B)lymphocyes

B)lymphocyes

ii! hymus .educaes. pre)Tlymphocyes %rom -one marrow/ ma0ing ii! hymus .educaes. pre)Tlymphocyes %rom -one marrow/ ma0ing maure T)lymphocyes!

maure T)lymphocyes! os actve untl pu-ery! os actve untl pu-ery!

(3)

PRIMARY

PRIMARY LLYMPHOID YMPHOID ORGANSORGANS

+rimary lymphoid organs are where lymphocyes arise and maure in +rimary lymphoid organs are where lymphocyes arise and maure in hehe a-sence o% antgenic stm

a-sence o% antgenic stmuli! uli! They are he -one mThey are he -one marrow and harrow and hymus!ymus!

Bone marrow: Bone marrow:

he so tssue in he hollow cener o% -ones he so tssue in he hollow cener o% -ones

Source o% all hemaopoietc progenior (sem* cells/ sie o% B cell mauraton Source o% all hemaopoietc progenior (sem* cells/ sie o% B cell mauraton pos)-irh in mammals!

pos)-irh in mammals!

hemaopoietc sem cell hemaopoietc sem cell

sromal sem cell  secrees sromal sem cell  secrees cyo0ines %or he stmulaton o% B) cyo0ines %or he stmulaton o% B) cell mauraton

(4)

Thymus

Thymus

•Bilo-ed organBilo-ed organ

•Locaed in he anerior mediastnum o% he horacic caviy anerior o he racheaLocaed in he anerior mediastnum o% he horacic caviy anerior o he rachea

and hear

and hear and grea vessels and poserior o and grea vessels and poserior o sernum!sernum!

•Sie where lymphoid cells undergo mauraton and educaton ino T cells prior oSie where lymphoid cells undergo mauraton and educaton ino T cells prior o

release ino he circulaton! This process allows T cells o develop he imporan release ino he circulaton! This process allows T cells o develop he imporan a3ri-ue

a3ri-ue 0nown 0nown as as sel%)olerance!sel%)olerance!

•4specially imporan in new-orn -a-ies wihou a hymus a -a-y5s immune4specially imporan in new-orn -a-ies wihou a hymus a -a-y5s immune

sysem collapses and he -a-y will die sysem collapses and he -a-y will die

•6raduall6radually enlarges during y enlarges during childhoodchildhood

•Aer pu-ery i undergoes a process o% involuton resultng in a reducton in heAer pu-ery i undergoes a process o% involuton resultng in a reducton in he

%unctoning mass o% he gland! 7 contnues o %uncton hroughou li%e/ however! %unctoning mass o% he gland! 7 contnues o %uncton hroughou li%e/ however!

(5)
(6)
(7)

A! Sroma A! Sroma

1!

1! capsulecapsule 2! r

2! ra-eculae (sra-eculae (srands o% ands o% connectve connectve tssue intssue ino parenco parenchyma*hyma* a!

a! lo-ules lo-ules (ouer (ouer corecorex x 8 8 inner inner medulla*medulla* &! 7ner

&! 7nerdigiatng digiatng dendritc cells dendritc cells  ma0 ma0e ore organ %rgan %rameowr0ameowr0 conri-ue

(8)

B! +arenchyma B! +arenchyma 1! 1! corexcorex a! immaure T lymphocyes a! immaure T lymphocyes

7mmaure lymphoid cells ener he

7mmaure lymphoid cells ener he corex/ where hey proli%ercorex/ where hey proli%erae/ maure/ and move o heae/ maure/ and move o he medulla/ %rom where maure T lymphocyes ener he

medulla/ %rom where maure T lymphocyes ener he circulaton!circulaton! 9urse cells  hymic epihelial cells

9urse cells  hymic epihelial cells wih long mem-rane exensionswih long mem-rane exensions :ortcal epihelial cells

(9)

2! medulla 2! medulla

a!

a! T T lymphocyes lymphocyes ener ener venulesvenules -!

-! ;assall<s ;assall<s corpusccorpuscles les  eosinophilic solid

(10)

:! ;isophysiology :! ;isophysiology

1!

1! T T lymphocyes lymphocyes originae originae in in -one-one marrow

marrow 2!

2! involuton involuton aer aer pu-erypu-ery a!

a! parenchyma parenchyma replaced replaced -y -y %a%a &!

(11)

Secondary Lymphoid >rgans

Secondary Lymphoid >rgans

+eripheral lymphoid organs? lymph nodes/ spleen/

+eripheral lymphoid organs? lymph nodes/ spleen/

onsils/ adenoids/ and lymphoid tssue associaed wih

onsils/ adenoids/ and lymphoid tssue associaed wih

oher organ sysems (gu/ s0in/ mucosa*!

oher organ sysems (gu/ s0in/ mucosa*!

Along he vessels o% lymphatc sysem

Along he vessels o% lymphatc sysem

conrol he ,ualiy o% immune responses

conrol he ,ualiy o% immune responses

@ell organied 8 encapsulaed  Spleen 8 Lymph

@ell organied 8 encapsulaed  Spleen 8 Lymph

nodes

nodes

=iused 8 unencapsulaed aggregaton o% lymphoid

=iused 8 unencapsulaed aggregaton o% lymphoid

tssues

(12)

•=ierences among he various lymphatc tssues signi'canly=ierences among he various lymphatc tssues signi'canly

aec he %orm o% immuniy and relae o how antgens are aec he %orm o% immuniy and relae o how antgens are ac,uired -y hese organs 

ac,uired -y hese organs 

lymph nodes are 'lers o% lymph/ lymph nodes are 'lers o% lymph/ spleen is a 'ler o% -lood/ and

spleen is a 'ler o% -lood/ and

mucosal associaed lymphatc tssues ac,uire antgens -y mucosal associaed lymphatc tssues ac,uire antgens -y ranscyosis o lymphoid tssue %rom he .exernal. ranscyosis o lymphoid tssue %rom he .exernal. environmen across specialied %ollicle)associaed epihelial environmen across specialied %ollicle)associaed epihelial cells

(13)

This drawing simpli'es srucures and connectons o% secondary lymphatc tssues where antgen may This drawing simpli'es srucures and connectons o% secondary lymphatc tssues where antgen may mos eCcienly direc immune responses! ultple 0nown and un0nown %acors inrinsic o he mos eCcienly direc immune responses! ultple 0nown and un0nown %acors inrinsic o he microenvironmens o% lymph node/ spleen and mucosa associaed lymphatc tssue (here ALT is microenvironmens o% lymph node/ spleen and mucosa associaed lymphatc tssue (here ALT is represened -y +eyer5s paches* in$uence wheher a .peripheral. or .mucosal. ype o% response represened -y +eyer5s paches* in$uence wheher a .peripheral. or .mucosal. ype o% response occurs! The drawing also indicaes ha hese tssues are inegraed wih each oher and he res o% occurs! The drawing also indicaes ha hese tssues are inegraed wih each oher and he res o% he individual hrough vascular and lymphatc connectons and a sysem o% lymphocye recirculaton! he individual hrough vascular and lymphatc connectons and a sysem o% lymphocye recirculaton!

(14)

Lymph 9odes

Lymph 9odes

4ncapsulaed 8 -ean shaped conaining lymphocyes/ macrophages 8 =:<s in 4ncapsulaed 8 -ean shaped conaining lymphocyes/ macrophages 8 =:<s in a retcular newor0

a retcular newor0

"iler lymphatc $uidD "iler lymphatc $uidD

Sies o% Ag presenaton 8 cell raCc Sies o% Ag presenaton 8 cell raCc

"irs organied lymphoid srucure o encouner Ag<s ha ener tssue spaces "irs organied lymphoid srucure o encouner Ag<s ha ener tssue spaces

Cortex Cortex Cortical nodules Cortical nodules   (follicles)   (follicles) Medullary Medullary  sinuses  sinuses

(15)

Functons o s!ruc!ura" e"emen!s o "ym#h no$es

Functons o s!ruc!ura" e"emen!s o "ym#h no$es

Subcapsular  Subcapsular    Sinus

  Sinus

Lymphatc sysem ) a series o% vessels which drain and 'ler he Lymphatc sysem ) a series o% vessels which drain and 'ler he tssue $uids!

tssue $uids!

Lymph eners he node via aeren lymphatcs/ passes hrough he Lymph eners he node via aeren lymphatcs/ passes hrough he sinuses lined wih macrophages and leaves via eeren lymphatc sinuses lined wih macrophages and leaves via eeren lymphatc (ultmaely all drain ino he poral vein*!

(16)

Lymphocyes ener he node primarily %rom he -lood via ;4E Lymphocyes ener he node primarily %rom he -lood via ;4E and leave via eeren lymphatcs!

and leave via eeren lymphatcs!

=:s migratng %rom tssue ener he node ino he T cell areas! =:s migratng %rom tssue ener he node ino he T cell areas!

B cells enering nodes %rom -lood mus cross he T rich area in B cells enering nodes %rom -lood mus cross he T rich area in ransi o

ransi o he B cell rich areas hus he B cell rich areas hus optmiing optmiing TT)B coopera)B cooperaton!ton! The B cell rich areas conain maure/ restng B cells organied The B cell rich areas conain maure/ restng B cells organied ino srucures around %ollicular dendritc cells (primary ino srucures around %ollicular dendritc cells (primary %ollicles*!

(17)

A! 6ross Anaomy A! 6ross Anaomy

1! -ean shaped/ wih hilus 1! -ean shaped/ wih hilus 2!

2! aeren aeren 8 8 eereeren en lymphatcslymphatcs &!

&! locaed locaed hroughou hroughou -ody -ody along along lymphatcslymphatcs

B! Sroma B! Sroma 1! capsule 1! capsule 2! 2! ra-eculaera-eculae &!

(18)

:! +arenchyma :! +arenchyma

1!

1! su-capsular su-capsular sinussinus a!

a! diagnodiagnostc stc %eaure%eaure

2!

2! corexcorex a!

a! lymph lymph nodulesF%ollinodulesF%olliclescles 1* B lymphocyes

1* B lymphocyes

 -! inner corex F paracorex  -! inner corex F paracorex

1* T lymphocyes 1* T lymphocyes c!

c! inermediae inermediae F F ra-ecular ra-ecular sinusessinuses

&!

&! medullamedulla

a! medullary cords (B cells* a! medullary cords (B cells* -!

(19)

+arenchyma ) hree componens? +arenchyma ) hree componens?

G G corexcorex G G paracorexparacorex G G medullamedulla

G :orex (B cell area* G :orex (B cell area*

+rimary %ollicle s (lymphocyes / mosly restng B cells/ +rimary %ollicle s (lymphocyes / mosly restng B cells/

macrophages 8 "=:<s* macrophages 8 "=:<s*

Ag challange Ag challange

Secondary %ollicles  conains germinal cener (discree Secondary %ollicles  conains germinal cener (discree lymphoid comparmens where

lymphoid comparmens where B%ce""sB%ce""s  undergo division/  undergo division/ isoype swiching and memory developmen*

(20)

B cells B cells

via ;4 via ;4EEss

7n lymph node 7n lymph node

7n %ollicles 7n %ollicles

Stmulaed B cells ) proli%erae and remain in he node! Stmulaed B cells ) proli%erae and remain in he node!

Actvaed B cells wihin he lymphoid %ollicles )

Actvaed B cells wihin he lymphoid %ollicles )  follicle centr follicle centre e cells cells --centroblasts ( 

centroblasts ( cells wih cleaved nucleicells wih cleaved nuclei )  ) centrocytes centrocytes ( ( cells wihcells wih larger more open nuclei and several nucleoli

larger more open nuclei and several nucleoli  ) ) o paracorex 8o paracorex 8 medullary

medullary sinuses sinuses immuno-lasimmuno-lass s plasma plasma cellsFmemorycellsFmemory cells

cells

The pale saining cenral area o% a secondary %ollicle )

The pale saining cenral area o% a secondary %ollicle ) germinalgerminal centre

centre  ) surrounded -y a manle one o% small/ naive B cells and a  ) surrounded -y a manle one o% small/ naive B cells and a %ew T cells

%ew T cells

(21)
(22)

B cells alone are no a-le o moun immune responses! They B cells alone are no a-le o moun immune responses! They are assised -y accessory cells?

are assised -y accessory cells? G

G sinus sinus macrophages macrophages (highly (highly phagocytc*phagocytc* G

G tngi-le tngi-le -ody -ody macrophages macrophages (inges (inges cellular cellular de-ris de-ris inin germinal cenres*

germinal cenres* G

G marginal marginal one one macrophages macrophages (%ound (%ound -eneah -eneah hehe su-capsular sinus*

su-capsular sinus* G

(23)

B cell differentiation in the germinal center

B cell differentiation in the germinal center

B cell differentiation in the germinal center

B cell differentiation in the germinal center

centrocyte centrocyte FDC FDC mature mature B cell B cell helper helper T cell T cell bacteria bacteria LIGHT  LIGHT  ZON ZON !CL"## #$ITCH !CL"## #$ITCH %CO&BIN"TION %CO&BIN"TION !#O&"TIC !#O&"TIC H'(%&)T"TION H'(%&)T"TION D"%* ZON D"%* ZON

Centrobla+t

Centrobla+t

apoptosis apoptosis anergic anergic Memory Memory B cell B cell Plasma B cell Plasma B cell

(24)

+ar

+aracorex (T celacorex (T cell area*l area*

•conains lymphocyes and accessory cells along wihconains lymphocyes and accessory cells along wih

supportng cells! supportng cells!

•predominan sie %or T cells wihin he lymph node!predominan sie %or T cells wihin he lymph node! •

•The various ypes o% T cell ener he node %rom he -lood viaThe various ypes o% T cell ener he node %rom he -lood via

he ;4Es! @hen actvaed hey %orm lympho-lass/ which he ;4Es! @hen actvaed hey %orm lympho-lass/ which divide o produce a clone o% T cells responding o a speci'c divide o produce a clone o% T cells responding o a speci'c antgen! Actvaed T cells hen pass ino he circulaton o reach antgen! Actvaed T cells hen pass ino he circulaton o reach peripheral sies!

peripheral sies!

•Accessory cells? 7nerdigiatng cells are numerous in heAccessory cells? 7nerdigiatng cells are numerous in he

paracore

(25)
(26)

edulla edulla

comprised o%? comprised o%?

G

G large large -lood -lood vesselsvessels G

G medullary medullary cordscords G

G medullary medullary sinusessinuses

•The medullary cords are rich inThe medullary cords are rich in plasma  plasma cellscells/ which produce A-/ which produce

A-ha pass ou o% he node via he eeren lymphatc! ha pass ou o% he node via he eeren lymphatc!

Macrophages

Macrophages are also numerous wihin he medulla! are also numerous wihin he medulla!

•Lymph passes ino he node hrough he aeren lymphatcLymph passes ino he node hrough he aeren lymphatc

ino he marginal sinus/ hough he cortcal sinuses o reach he ino he marginal sinus/ hough he cortcal sinuses o reach he medullary sinuses -e%ore leaving via he eeren lymphatc!

(27)

•+artculae ma3er in he lymph is removed -y macrophages!+artculae ma3er in he lymph is removed -y macrophages!

Antgens are a0en up -y antgen presentng cells and hese Antgens are a0en up -y antgen presentng cells and hese %aciliae he speci'c immune response!

%aciliae he speci'c immune response!

•Less han 1IJ o% lymphocyes ener he node in he lymph/Less han 1IJ o% lymphocyes ener he node in he lymph/

he large maKoriy enering %rom he -lood via he ;4Es! he large maKoriy enering %rom he -lood via he ;4Es!

7n%ectonF

7n%ectonFAg challAg challengeenge

"iy %old increase in lymphocyes in eeren lymph vessel han "iy %old increase in lymphocyes in eeren lymph vessel han

in aeren lymph vessel (@hy* in aeren lymph vessel (@hy*

(28)

a highly vascular ducless organ ha is locaed in he le a-dominal

a highly vascular ducless organ ha is locaed in he le a-dominal region near heregion near he somach or inestne o% mos vere-raes and is concerned wih 'nal desructon o% somach or inestne o% mos vere-raes and is concerned wih 'nal desructon o% red -lood cells/ 'lraton and sorage o% -lood/ and producton o%

red -lood cells/ 'lraton and sorage o% -lood/ and producton o% lymphocyeslymphocyes

Spleen? de'niton(s*

Spleen? de'niton(s*

(29)
(30)

Two distnc componens o% he spleen ) red pulp and he whie Two distnc componens o% he spleen ) red pulp and he whie pulp

pulp

#ed pulp ) large num-ers o% sinuses and sinusoids 'lled wih #ed pulp ) large num-ers o% sinuses and sinusoids 'lled wih -lood ) responsi-le %or he 'lraton %uncton o% he spleen!

-lood ) responsi-le %or he 'lraton %uncton o% he spleen!

@hie pulp ) aggregaes o% lymphoid tssue ) responsi-le %or he @hie pulp ) aggregaes o% lymphoid tssue ) responsi-le %or he immunological %uncton o% he spleen!

immunological %uncton o% he spleen!

PALS PALS

Spleen

Spleen

(31)

aKor %unctons? aKor %unctons?

G7 is responsi-le %or he desructon o% old red -lood cells G7 is responsi-le %or he desructon o% old red -lood cells (#B:s*D

(#B:s*D

G7 is a maKor sie %or mountng he immune response! G7 is a maKor sie %or mountng he immune response!

"ilers -lood ) Blood enering he spleen ravels hrough "ilers -lood ) Blood enering he spleen ravels hrough progressively smaller arerioles untl i is deposied in he red progressively smaller arerioles untl i is deposied in he red pulp/

pulp/ where where he he #B:s #B:s are are processed! processed! Surrounding Surrounding hehe arerioles is a sheah o% lymphoid cells/ which ma0e up he arerioles is a sheah o% lymphoid cells/ which ma0e up he

 periarteri

 periarteriolar olar lymphoid lymphoid sheath sheath (P(PALS)ALS)! The iner%ace -eween! The iner%ace -eween +ALS and -lood is a region o% inense phagocytc actviy and +ALS and -lood is a region o% inense phagocytc actviy and ses he sage %or immune responses! The immune reactviy o% ses he sage %or immune responses! The immune reactviy o% he spleen is especially eectve %or dealing wih -lood)-orne he spleen is especially eectve %or dealing wih -lood)-orne antgens such as -aceria!

(32)

INSID& TH& SPL&&N INSID& TH& SPL&&N

Red Red pulp pulp

Re$ #u"#

Re$ #u"#

;as a complex sysem o% -lood ;as a complex sysem o% -lood vessels wihin i/ arranged o vessels wihin i/ arranged o %aciliae removal o% old or %aciliae removal o% old or damaged red -lood cells %rom he damaged red -lood cells %rom he circulaton!

circulaton!

A small proporton o% splenic A small proporton o% splenic -lood $ow passes hrough more -lood $ow passes hrough more rapidly wihou undergoing rapidly wihou undergoing 'lraton!

(33)

Whit Whit e e pulp pulp Primary Primary follicle follicle Margin Margin alzone alzone Periarterial Periarterial lymphatic lymphatic sheath (PALS) sheath (PALS) Germinal center Germinal center Artery Artery Vein Vein Red pulp Red pulp Vascular Vascular sinusoids sinusoids    ra!eculara!ecula "apsule "apsule

:onains T cells/ B cells and

:onains T cells/ B cells and accessory cells!accessory cells!

Similar wih lymph node

Similar wih lymph node srucure in many respecs!srucure in many respecs!

+urpose ) o moun an

+urpose ) o moun an immunological reimmunological response o antgens wihin he -loodsponse o antgens wihin he -lood

+resen in he %orm o% a periareriolar lymphoid sheah ) conains B cell %ollicles +resen in he %orm o% a periareriolar lymphoid sheah ) conains B cell %ollicles and T cells! A he edge o% he T one ) marginal one ) larger lymphocyes and and T cells! A he edge o% he T one ) marginal one ) larger lymphocyes and antgen presentng dendritc cells are locaed!

antgen presentng dendritc cells are locaed!

'h(!e #u"#

'h(!e #u"#

(34)

A! Sroma A! Sroma 1! 1! capsulecapsule 2! 2! ra-eculaera-eculae &!

&! retcular retcular '-ers'-ers

B! +arenchyma F Splenic +ulp B! +arenchyma F Splenic +ulp

1!

1! whie whie pulppulp 2! red pulp 2! red pulp &!

&! splenic splenic areryarery a!

a! ra-ecular ra-ecular areriesareries -!

-! cenral cenral areriesareries 1*

1* ++ALSALS c!

c! splenic splenic sinusoidssinusoids d!

d! ra-ecular ra-ecular veinsveins e!

(35)

:! @hie pulp :! @hie pulp 1! 1! ++ALSALS a! T lymphocyes a! T lymphocyes =! #ed pulp =! #ed pulp 1!

1! splenic splenic cordscords

a! B8T lymphocyes a! B8T lymphocyes -!

-! retcular retcular cellscells c!

c! plasma plasma cellscells d!

d! macrophagesmacrophages 2!

(36)

4! ;isophysiology 4! ;isophysiology

1! lymphocye producton 1! lymphocye producton

a!

a! whie whie pulppulp

2! eryhrocye removal 2! eryhrocye removal

a!

a! macrophagesmacrophages &! immune de%ense &! immune de%ense

a!

a! B B and and T T cellscells -!

-! macrophagesmacrophages Mcleanses he -loodN Mcleanses he -loodN

Msimilar %unctons carried ou -y liver/ oher lymph organsN Msimilar %unctons carried ou -y liver/ oher lymph organsN

(37)

9onencapsulaed su-mucosal lymphoid nodules and diuse lymphocytc in'lraes in he 9onencapsulaed su-mucosal lymphoid nodules and diuse lymphocytc in'lraes in he su-mucosa o% inestnal and respiraory racs

su-mucosa o% inestnal and respiraory racs

consiss o% aggregaes o% lymphocyes/ macrophages/ =:s/ and oher accessory cells consiss o% aggregaes o% lymphocyes/ macrophages/ =:s/ and oher accessory cells Sca3ered hroughou he lamina propia in he gu

Sca3ered hroughou he lamina propia in he gu

@or0 collectvely wih regional lymph nodes and spleen o produce B) and T)eecor cells which @or0 collectvely wih regional lymph nodes and spleen o produce B) and T)eecor cells which lodge in lamina propria and in inraepihelial locatons wherever here is mucosa

lodge in lamina propria and in inraepihelial locatons wherever here is mucosa

9asopharyngeal lymphatc tssues (ie onsils and adenoids in man*/ -ronchus associaed lymphatc 9asopharyngeal lymphatc tssues (ie onsils and adenoids in man*/ -ronchus associaed lymphatc tssues/ +eyer5s paches/ appendix and isolaed %ollicles in inesttnal mucosae

tssues/ +eyer5s paches/ appendix and isolaed %ollicles in inesttnal mucosae

Eary wih regard o ype o% sur%ace epihelium (sat'ed s,uamous/ ciliaed columnar/ or a-sorptve Eary wih regard o ype o% sur%ace epihelium (sat'ed s,uamous/ ciliaed columnar/ or a-sorptve columnar* and relatve proportons o% T) and B)cells

columnar* and relatve proportons o% T) and B)cells All have .. cells in heir

All have .. cells in heir %ollicle associae epihelium%ollicle associae epihelium

ucosal lymphatc tssues ampli%y developmen o% commi3ed B)cells %or secreory 7gA responses o ucosal lymphatc tssues ampli%y developmen o% commi3ed B)cells %or secreory 7gA responses o enviromenal antgens and programs cerain environmenal antgens %or sysemic olerance enviromenal antgens and programs cerain environmenal antgens %or sysemic olerance inducton which does no eec producton o% B)cells commi3ed o 7gA secreton!

inducton which does no eec producton o% B)cells commi3ed o 7gA secreton!

.ucosal. olerance is mani%esed -y antgen)speci'c suppression o% delayed cuaneous .ucosal. olerance is mani%esed -y antgen)speci'c suppression o% delayed cuaneous hypersensitviy and reduced 7g6 expression

hypersensitviy and reduced 7g6 expression Large populaton o% ant-ody)pr

Large populaton o% ant-ody)producing plasma cells oducing plasma cells (%ar more han plasma cells (%ar more han plasma cells in he in he spleen/spleen/

M)*OSA%ASSO*IAT&D LYMPHOID TISS)& +MALT, M)*OSA%ASSO*IAT&D LYMPHOID TISS)& +MALT,

(38)
(39)

>uer mucosal epihelial layer conains so)called

>uer mucosal epihelial layer conains so)called (n!rae#(!he"(a" "ym#hocy!es +I&Ls,-(n!rae#(!he"(a" "ym#hocy!es

+I&Ls,-lamina propria/ lies under he epihelial layer/ conains large num-ers o% B cells/ plasma cells/ actvaed lamina propria/ lies under he epihelial layer/ conains large num-ers o% B cells/ plasma cells/ actvaed T; cells/ and macrophages in loose clusers!

T; cells/ and macrophages in loose clusers!

Su-mucosal layer -eneah he lamina propria conains +eyer<s paches/ nodules o% &IOI lymphoid Su-mucosal layer -eneah he lamina propria conains +eyer<s paches/ nodules o% &IOI lymphoid %ollicles

%ollicles

Large aggregaes o% 6ALT have distnc B cell %ollicles and T cell areas! Antgen presentng accessory cells Large aggregaes o% 6ALT have distnc B cell %ollicles and T cell areas! Antgen presentng accessory cells are also presen!

are also presen!

Lymphocyes %orm domed %ollicles o% B cells surrounded -y T cells! Lymphocyes %orm domed %ollicles o% B cells surrounded -y T cells!

+eyer5s paches %aciliae he generaton o% an immune response wihin he mucosa! B cell precursors +eyer5s paches %aciliae he generaton o% an immune response wihin he mucosa! B cell precursors and memory cells are stmulaed -y Ag in +eyer5s paches! :ells pass o he meseneric lymph nodes and memory cells are stmulaed -y Ag in +eyer5s paches! :ells pass o he meseneric lymph nodes where he immune response is ampli'ed! Actvaed lymphocyes pass ino he -lood sream via he where he immune response is ampli'ed! Actvaed lymphocyes pass ino he -lood sream via he horacic duc! These cells hen home in he

horacic duc! These cells hen home in he gu and carry ou heir gu and carry ou heir 'nal eec'nal eecor %unctons!or %unctons! ;4Es are no presen in +eyer5s paches!

;4Es are no presen in +eyer5s paches!

9o aeren lymphatcs and no medullary cords %or local accumulaton o% plasma cells 9o aeren lymphatcs and no medullary cords %or local accumulaton o% plasma cells

G)T%ASSO*IAT&D LYMPHOID TISS)& +GALT, G)T%ASSO*IAT&D LYMPHOID TISS)& +GALT,

(40)

Some epihelial cells have complex micro%olds in heir sur%aces! Pnown as

Some epihelial cells have complex micro%olds in heir sur%aces! Pnown as M (mul-M (mul- fenestr

 fenestrated) ated) cell cell s/ $a3ened epihelial cells lac0ing he microvilli/ hey collec Ags/ $a3ened epihelial cells lac0ing he microvilli/ hey collec Ag (endocyose and ranspor various maerials wihou lysomal degradaton*!

(endocyose and ranspor various maerials wihou lysomal degradaton*!

 cells have a deep invaginaton/ or poc0e/ in he -asolaeral plasma mem-raneD  cells have a deep invaginaton/ or poc0e/ in he -asolaeral plasma mem-raneD his poc0e is 'lled wih a cluser o% B cells/ T cells/ and

his poc0e is 'lled wih a cluser o% B cells/ T cells/ and macrophages!macrophages!

Q Luminal antgens are endocyosed ino vesicles ha are ranspored %rom he Q Luminal antgens are endocyosed ino vesicles ha are ranspored %rom he luminal mem-rane o he un

luminal mem-rane o he underlying poc0e mem-rane!derlying poc0e mem-rane!

Q The vesicles hen %use wih he poc0e mem-rane/ delivering he poentally Q The vesicles hen %use wih he poc0e mem-rane/ delivering he poentally response)actvatng antgens o he clusers o% lymphocyes conained wihin he response)actvatng antgens o he clusers o% lymphocyes conained wihin he poc0e!

poc0e!

Q  cells are locaed in so)called

Q  cells are locaed in so)called (n$uct.e s(!es/sma"" re0(ons o a(n$uct.e s(!es/sma"" re0(ons o a mucousmucous mem-rane ha lie

mem-rane ha lie over organiover organied lymphoid ed lymphoid %ollic%ollicles!les!

Q Antgens ranspored across he mucous mem-rane -y  cells can actvae B cells Q Antgens ranspored across he mucous mem-rane -y  cells can actvae B cells wihin hese lymphoid

wihin hese lymphoid %ollicles!%ollicles!

Q The actvaed B cells dierentae ino plasma cells/ which leave he %ollicles and Q The actvaed B cells dierentae ino plasma cells/ which leave he %ollicles and secree he 7gA class o% ant-odies

(41)

ORGANI1ATION OF GALT ORGANI1ATION OF GALT follicle#associated follicle#associated epithelium epithelium follicular $" follicular $" Peyer%s Peyer%s patch patch & cells in & cells in domed follicle

domed folliclecentro!lastcentro!last & cells & cells   cells   cells 'illi 'illi M cell M cell gut lumen gut lumen high high endothelial endothelial 'enule 'enule lamina lamina propria propria lymphatic lymphatic netor netor

(42)

T

Tons

onsil

il anao

anaomy

my

• +haryngeal onsils+haryngeal onsils •

• +alatne onsils+alatne onsils •

• Lingual onsilsLingual onsils •

• Aggregatons o% lymphAggregatons o% lymph

nodules nodules

"rom human anaomy ex "rom human anaomy ex

(43)

 Tonsils

 Tonsils

A! aggregatons o% lymph nodules A! aggregatons o% lymph nodules B!

B! incompleincompleely eely encapsulancapsulaeded :! cryps

(44)

 Tonsils

 Tonsils

=! +alatne onsils =! +alatne onsils 1! 1! pharynxpharynx 2!

2! srasrat'ed t'ed s,uamous s,uamous epiheliumepihelium &!

&! crypscryps

4! +haryngeal onsils 4! +haryngeal onsils 1! 1! pharynxpharynx 2! 2! +S::+S:: "! Lingual onsils "! Lingual onsils 1!

1! -ase -ase o% o% ongueongue 2!

2! srasrat'ed t'ed s,uamous s,uamous epiheliumepihelium &!

(45)

S2IN%ASSO*IAT&D LYMPHOID TISS)& +SALT, S2IN%ASSO*IAT&D LYMPHOID TISS)& +SALT,

:ells o% SALT include 0eratnocyes/ Langerhans cells (immaure =:s %ound in s0in*/ :ells o% SALT include 0eratnocyes/ Langerhans cells (immaure =:s %ound in s0in*/ inraep

inraepiehelial T iehelial T cells/ and cells/ and melanocymelanocyes!es! ononuclear phagocy

ononuclear phagocyes in es in perivenular locatperivenular locatons in ons in he super'cial dermishe super'cial dermis

Langerhans cells %orm a contnuous epidermal meshwor0? hey capure Ag/ hen migrae Langerhans cells %orm a contnuous epidermal meshwor0? hey capure Ag/ hen migrae o draining lymph nodes/ where hey ac

o draining lymph nodes/ where hey ac as Ag)presentng cells!as Ag)presentng cells! The maKoriy o% T cells

The maKoriy o% T cells are %ound in he dermal layer o% s0in!are %ound in he dermal layer o% s0in!

+assenger leu0ocye ha initaes allogra reKecton via antgenF:lass 7 ;: expression is +assenger leu0ocye ha initaes allogra reKecton via antgenF:lass 7 ;: expression is also a

also a Lan0erhans ce""Lan0erhans ce""/ and removal o% he cell or a-laton o% he aeren lymphatcs/ and removal o% he cell or a-laton o% he aeren lymphatcs prevens sensitaton

prevens sensitaton The epidermis also

The epidermis also conconainsains intraepidermal lymphocytes,intraepidermal lymphocytes, similar o he similar o he inraepiheinraepiheliallial lymphocyes o% ALT in ha mos o% hem are :=R T cells/ many o% which express T)cell lymphocyes o% ALT in ha mos o% hem are :=R T cells/ many o% which express T)cell recepors/ which have limied diversiy %or antgen!

recepors/ which have limied diversiy %or antgen!

Q These inraepidermal T cells are well siuaed o encouner antgens ha ener hrough Q These inraepidermal T cells are well siuaed o encouner antgens ha ener hrough he s0in and may play a role in com-atng antgens ha ener hrough he s0in!

he s0in and may play a role in com-atng antgens ha ener hrough he s0in!

Q The underlying dermal layer o% he s0in conains sca3ered :=O and :=R T cells and Q The underlying dermal layer o% he s0in conains sca3ered :=O and :=R T cells and macrophages!

macrophages! Q os o% hese

(46)

SALT SALT

References

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