NK 15 - Lymphoid Organs.doc
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Transcript of NK 15 - Lymphoid Organs.doc
8/10/2019 NK 15 - Lymphoid Organs.doc
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LYMPHOID ORGANS
highly localized microenvironments are strctral !asis o" immne res#onse
lym#hocyte s#eci"icity is $ite rare% as is their dis#ersement throghot the !ody
soln& highly orchestrated movements o" antigen
' "nctional environments ()* PRIMARY lym#hoid organs ( matre !t na+ve lym#hocyte #rodction,* S-.ONDARY ( mechanism o" co/localizing antigens and lym#hocytes'* 0-R0IARY ( sites o" in"ection mst !e a!le to srvey "or it and also reglate
the in"l1 o" e""ector cells
PRIMARY LYMPHOID 0ISS2- ( !one marro3 and thymsantigen recognition develo#ment
#ositive4negative selectionsignaling a##arats in res#onse to antigenic stimlationca#acity to home to #ro#er microenvironment
5ON- MARRO6 ( "or 5 .ellscontains no lym#hatic channels !t is vasclarized
hemato#oetic stem cells are nestled ne1t to osteo!lasts and receivesrvival signals "rom them
antigen inde#endent matration o" 5/cells
very ine""icient #rocess 7"rameshi"t recom!inations* #ro/thymocyte also is made "rom hemato#oetic stem cell
stromal cells& s##ort develo#ment4matration o" lym#hocytes in marro3secrete cyto8ines 7IL/9*
./:I0 and stem cell "actor interact on 5/cell sr"ace "or lym#ho#oesiscell/cell contact 34 stromal cells also directs lym#ho#oesis
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0HYM2S ( many e#ithelial/derived cells.OR0-;&
.APS2L- < lining= invaginates to "orm lo!eslined 34 early 0/cell #rogenitors
.ortical -#ithelial .ells ( dendridic cells% stimlate 0/cell matration
Macro#hages ( clearance o" n#rodctive rearrangements
Interdigitating .ells ( !ondary !et3een corte1 and medllaalso called >thymic dendridic cells? !one/marro3 derivedMH.I4MH.II #resentation
Localization o" 0/.ell Develo#ment/ #rogenitors enter via ca#sle"irst re#licate then ndergo gene [email protected] develo#ed that also have #rodctive a4! 0.R recom!ination
.ortical 0hymocytes then associate 3ith e#ithelial cells #ositive selC.D@ OR .DB singly #ositive cells can #roceed !ased onMH.I vs MH.II a""inity
Interdigitating .ells ( drive negative selection 7sel"/recognition*
still nclear as to 3hether #ositive or negative selection occrs "irst
Stains&cyto8eratin ( stains "or e#ithelial 7dendridic* cells in thyms.DB ( stains "or any cell 3ith .DB 7do!le/#ositives also stain*
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S-.ONDARY LYMPHOID 0ISS2-S ( lym#h nodes 7tre and msocal*% s#leen/ mechanisms "or AP. or antigen to access necessary microenvironment "rom siteo" in"ection
/ s#ecialized vasclarization 7lym#hatics and high endothelial venles* to recrit
lym#hocytes and send them !ac8 ot 7e""ect lym#hatics*
/ distinct regions "or 5 7"ollicles* and 0 cell #riming 7!et3een "ollicles*
EOLLI.L-S ( #rimary "ollicles ( 5 cells have not yet encontered antigensecondary "ollicles ( ra#id gro3th o" 5 cells a"ter antigenic e1#osre
germinal center and marginal zone
Lym#hocyte com#artmentalization is a directed #rocesschemo8ine secretion !y H-F to recrit lym#hocytes ot o" !lood
activated e""ector cells no longer e1#ress chemo8ine rece#tors
EOLLI.2LAR dendridic cells / not !one marro3 derived= NO0 AP.sma8e chemo8ines 75L.* and organize "ollicles
H-F and Stromal cells secrete SL.4-L. attracts 0 cells-#ithelial Dendridic .ells 7AP.s* also res#ond to SL.
ensres Dendridic cells and 0/cells .OLO.ALI-H-L4OFA e1#eriment demonstrated that 0 cellsmove to "olliclar areas #on antigen e1#osre%
casing 5 cell #roli"eration
Staining& .D, ( 5 cells .D' ( 0 cells
NAJF- -EE-.0OR 0RANSI0ION& occrs in lym#h nodes
0 cells& decreased activation threshold 7no costimlation*e""ector "nction activity 7hel#er or 8iller*homing ca#acity 7directed to tertiary% not secondary tisses*
5 cells& memory and e""ector 7#lasma* cellsa""inity matrationclass s3itching anti!ody secretion
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OF-RFI-6 (no antigen 5 and 0 cells come in "rom high endothelial venle
migrate to "ollicle4dendridic cellno antigen #resent so they L-AF- via the e""erent lym#athics
antigen #resent 5 cell enters and remains in "ollicle 7!inds sol!le antigen*antigen on dendridic cell cases .D@ 0H, di""erentiation.D@ #roli"erates and releases cyto8ines 7IL@4K4*
.D@ "ollo3s SL. and moves to "olliclar margin "or 045interaction
.D@L////[email protected]@ /////MH.&#e#tide.D,B ////59 7stim*.0LA@ /// 59 7inhi!*
migration occrs in the a!sence o" ..R9 rece#tors
localization is very im#ortant
5 cell #roli"eration and class s3itching
.D@L is not constittively e1#ressed !y all 0 cells% !t .D@ is !y 5 cellsre$ires that 0.R crosslin8ing "irst ta8es #lace
.D@ !inds .D@L
srvival advantage 7#reglates anti/a#o#otitic #roteins* #roli"eration#reglation o" costimlatory molecles "or 0 cells
G-RMINAL .-N0-R PROLIE-RA0IONclonal e1#ansion occrs in #resence o" antigen4.D@L
DAR: ON- 7centro!lasts*dring this #oint that hy#ermtation is ta8ing #lace
centro!lasts move to light zone no3 are .-N0RO.Y0-Sinteract 3ith "olliclar dendridic cells
di""erentiate into memory or #lasma cellsi" they !ind more antigen than dendridiccells