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IMMUNOLOGYIMMUNOLOGY

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IMMUNOLOGY : PREFACE

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IMMUNOLOGY : LAY OUT

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Innate immunity and decoding the patterns of self and nonself

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I. Introduction

II. Innate Immunity

1) What is the innate immunity?

2) Why is innate immunity so important?

3) Who are the members of innate immunity?

III. Decoding the patterns of self and nonself by the innate immunity

1) Immune logic: How do they recognize the pathogens?

2) Recognition of microbial nonself

3) Recognition of self

4) Recognition of altered self

IV. Self discrimination of adaptive immunity

V. References

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IMMUNOLOGY : INTRODUCTION

IMMUNOLOGY : INNATE IMMUNITY

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II. Innate Immune System

1. What is the innate immunity?

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IMMUNOLOGY : INNATE IMMUNITY

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2. Why is the innate immunity so important?

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Innate Innate Immune Immune systemsystem

Adaptive Adaptive Immune Immune systemsystem

II. Activation

I. Cooperation

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IMMUNOLOGY : INNATE IMMUNITY

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3. Who are the members of innate immunity?

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IMMUNOLOGY : BARRIER

7

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IMMUNOLOGY : PHAGOCYTES

8

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IMMUNOLOGY : NK CELL

9

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IMMUNOLOGY : LEUKOCYTE RECRUITMENT

10

BOX . 1 Leukocytes recruitmentBOX . 1 Leukocytes recruitmentDNHBMDKDBKNMFDGM

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B K@GFDL DGMDKM@KDMBDLADGCHBMHLL GCDIDGCDGMHEIDKEHKG@MHNMDM@KDMBDKDF@GLD@M@GCK@GFDL KDF@G@KFDLLLDJNDLMDKDCGDGCHBMB ODLBDLGMD@ALDGBDHEIDKEHKGLF@CHLDLHEIDKEHKG M@MB@NLDFGF@BDFDFAK@GDC@F@DB@GLGDKDMK@GFDL ,@GC-MHGCNBDK@IC@IHIMHLL

BOX . 2 Attack of NK cellBOX . 2 Attack of NK cell

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IMMUNOLOGY : DENDRITIC CELL

11

BOX . 3 BOX . 3 DendriticDendritic cellcell

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IMMUNOLOGY : DENDRITIC CELL

12

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IMMUNOLOGY : DEFENCE PROTEINS

13

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IMMUNOLOGY : CYTOKINES

14

. .+ R .

Bone marrow production of neutrophils, etc

IL-6

Limit inflammationIL-10, TGF-b

Macrophage activationIFN-r

Proliferation and activity of NK cells

IL-12, IL-15

Mediate local inflammationTNF, IL-1, chemokine

Control of viral infectionIFN-a, IFN-b

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9"BD "# B V I@HBMDL ] .9 L

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IMMUNOLOGY : S ELF DISCRIMINATION

15

">7DNF@MHC@KMKML

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1.Immune logic: How do they recognize the pathogens?

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%1KLMIKD@BMO@MHG-NMGDDCLIDKFLLHGEHKIKHEDLLHG@@MM@B

\+ V . 7 . W

7DBHGMHGHEFBKHA@GHGLDE7DBHGMHGHELDEF@KDK7DBHGMHGHEGCNBDCHK@MDKDCLDE

III. Decoding the patterns of Innate immunity

$W LDECLBKFG@MHG

72DCMHO.,@GD@ K/DBHCGMDI@MMDKGLHELDE@GCGHGLDE AMDGG@MDFFNGDLLMDF8BDGBD#'#!!##$!!

IMMUNOLOGY : SELF DISCRIMINATION

16

2. Recognition of microbial nonself(nonself marker + activating receptor)

W M - \ \M M LL R V . 4 . V \M B 5,25L5@MHDG@LLHB@MDCFHDBN@KI@MMDKGL V 5,25L > . 4 \M \` W W . \M + LNIIKDLLHK9BD$ V*

. 5,25L \ 58IHIHL@BB@KCD \ IDIMCHB@GV 5,25L . 5577L5@MMDKG KDBHGMHGKDBDIMHK 5,25L \M B M* ` M \V V 5,25L M V

577L 577L 5,25L M W * 577L ` \M` MV MW

577L . 97L9H DKDBDIMHK 97L 577L V

97L W FFNGM’LDD .4 B 5,25L M 2@BKHI@D W V97L 577L \M ‘` ’ . . 97L 97#97%97&97 5,25L M \ V 9 97L *V BHFAG@MHG R > 5,25L M > 577 97 5,25L M ] 97L B

97L W

\M V9 L*,BMO@MHGHELG@GI@M@LM@MGCNBD@GMFBKHA@DEEDBMHK KDLIHGLD

W L 7HDGMDGM@MHGHE@C@IMODFFNGDKDLIHGLDL

97L 5,25L M Q V VV ,5" 31- MK@GLBKIMHGE@BMHK L W L* 2@BKHI@D /DGCKMB BD \V V \ >

97 MMI LBDGBDGDLHK #!!"!! AHA@LI

"5,25

CL73,582@GGHLD:GFDM@MDC.I GNBDHMCD

#577

CL73,@BMO@MDCG@LD972@GGHLDKDBDIMHK

$8NIIKDLLHK9BDDIDK9BD` .MHMB 9BD ` ? . V 9BD` B W \ LNIIKDLLHK9BD W

IMMUNOLOGY : SELF DISCRIMINATION

17

97L /DGCKMB BD 9 V .HLMFN@MHK /DGCKMB BD 2. !VL \M \ 2. ! > MDIDK9BD CDGCKMB BD BHLMFN@MHK \ \M . L ` %M L,5. L +L DIDK9BD M + <BHLMFN@MHK \M 5,25L .577L B

3D@MODLDDBMHG-4& ` FBKHA@GCNBMHGHEBHLMFN@MHK FHDBNDL W B B *` +

3. Recognition of self (self marker + inhibitory receptor)

M 4 * M \ B * V 3BD 7 3BD B >\V 3BD . 4

. 4 * V .@LL2. B \M B > V `V > V \ .` 2. V < \V 2. 2. < V L 2. B + M

7 3BD 2." GAMHKKDBDIMHK M GAMHKKDBDIMHK 3BD + R1B KDBDIMHK + IL GAMHKKDBDIMHK +

GAMHKKDBDIMHK 92FFNGHKDBDIMHK MKHLGDGAMHKFHME 2." M . IHLIHK@MHGL* 92 85"` 85# MKHLGDIHLI@M@LD * 3BD L L \

L + 3BDB >V . W R .+ \

F_/^5/KH/]]/XZXZ`_/Z/c]X/Y/X/YX]X_/Y_/Z_X]/X/Xc/_cX/c`^/XZXZ_/ca`c/X_/Z_ZYZ`c/ca`c7

F_/^5/KH/]]/XZXZ`_/Z/c]X/Y/X/YX]X_/Y_/Z_X]/X/Xc/_cX/c`^/XZXZ_/ca`c/X_/Z_ZYZ`c/ca`c7

B \M IL 5 9BD +L M 7

> W <

V .9 + 2. L*\V V 3BD

V V V V \V V LL V B \V V V V > B\ V V . 4 V MKHLGDKDLCND + 5MKHLGDKDLCND ! \ \ \V GAMHKKDBDIMHK IHLI@M@LD * V L 3BD + ?

MB > ! .

IMMUNOLOGY : SELF DISCRIMINATION

18

2HDBN@K5@LLHKCL

+ GHGLDEB M+ M W NFHK@ FFNGM W * W L VVR> R> R>` + 5

"L L V R> V R> R> * ,BMOMHEBHFIDFDGMGOHODLMDLDJNDGM@IKHMDHLLHEIKHMDGLMHDGDK@MDDGFDLMIKHMDHMB @BMOM

# \M V \M \. \V \ V 9DIKHCNBMLHEBHFIDFDGM@BMO@MHGADBHFDBHO@DGM@MM@BDCMHFBKHA@BDLNKE@BDLHKMH@GMAHCDLAHNGCMHFBKHADL@GCMHHMDK@GMDGL-NM@DBHFIHGDGMHEMDBHFIDFDGM@LDKNFIKHMDGB@DC.$B@GBHO@DGM@GCGCLBKFG@MD@MM@BMLDEMHMDLNKE@BDLHE@NMHHHNL@GCFBKHA@BDL

$ + >+ VB . \M . R> .HFIDFDGM@BMO@MHGLGAMDCAKDN@MHKIKHMDGLM@M@KDIKDLDGMHGGHKF@HLMBDL@GC@ALDGMEKHFFBKHADL9LLADB@NLD@LDEBDLNAJNMHNLDIKDLLLDODK@DGDIKHCNBMLGBNCG./%'@GC./&&BGAMEHKF@MHGHEMD@BMOD.$BHGODKM@LD

5 Y + LDEF@KDK+ .$ .$A V ./%'` ./&& < VB .$BHGODKM@LD 2,.FDFAK@GD @MM@BBHFID \ V +L

CD47 : erythrocytes NZZ2&2. 2"Z2&F_-2Macrophage 22.

Sialic acids : FZ2&[" sialic acid Z. F Macrophage, dendritic cell, neutrophilZ.

CD46, CD55 : C3 JJNZ6Z. "ZC3 " C3 convertaseZQNZ.

MHC-1: 1#FZ2& KH/]]/ 1 7/ Y; 7

"W \ 5 \]

NFHK@ FFNGMBDFDC@MDCFFNGM

NFHK@ FFNGM V V . . ] \V V + < \V V BDFDC@MDCFFNGM

Absence of CD46,CD55

IMMUNOLOGY : MHC MOLECULES

19

BOX . 4 what is a MHC ?BOX . 4 what is a MHC ?

9DKHDHE2.IKHMDGLGAGCGEHKDG@GMDGL@GCIKDLDGMGMDFMH9BDLIKHOCDL@GDI@G@MHGEHKLHF@G9BDLKDLIHGCMHEHKDG2.FHDBNDL@GCMDKDAKDDBMEHKDGHK@GK@EML5KDLNF@AEHKDG2.IKHMDGLM@GDGCHDGHNLIDIMCDGMDKIDIMCDAGCGKHHODBKD@MDBHFIDDLM@MB@GKDLDFADLDE2.FHDBNDLBHFIDDC MEHKDGIDIMCDL8HFDBMHMHB 9BDBHGDLM@MKD@BMMH@OK@@GMDGG@LLHB@MHGM@LDEB@LL2.FHDBNDEHKD@FID@ODADDGLHGMHKD@BMMH@EHKDGB@LL2.FHDBNDGMD@ALDGBDHEMDOK@@GMDG

9D@GMDGIKDLDGMGENGBMHGHE2.IKHMDGLB@G@LHDI@GMDDMDGLODIHFHKILFHEMDLDFHDBNDLGMDDOHNMHG@K@KADMDDGI@MHDGBFBKHHK@GLFL@GCMDODKMDAK@MDFFNGDLLMDFFBKHHK@GLFLMDGCMHB@GDMDK@GMDGLMH@OHC@LLHB@MGM2.FHDBNDLDGHGDLNBBDDCLMAD@ADMHLDDIMKHN@IHIN@MHG@L@GDICDFBGLNBBKBNFLM@GBDLMDEDGCOCN@LM@MIKHCNBD@GD2.FHDBNDM@MB@G@LLHB@MDM@G@GMDGHEMD@MDKDCFBKHHK@GLF@OD@@KDLDDBMOD@CO@GM@DG@CCMHGGCOCN@LMMHCEEDKDGM@DDLEHKD@B2.FHDBNDDMDKHHMDL@OD@ADMMDKB@GBDHEKDLLMGGEDBMHGM@GMHLDMCDGMB@@DDL@M@GODG2.HBNL@LMD@OD@KD@MDKB@I@BMMHIKDLDGM@GMDGLEKHF@CDK@GDHEI@MHDGL9NLLDDBMHGMDGCMHIKHFHMD@GCF@GM@G@@KDCODKLMHE2.FHDBNDLGMDIHIN@MHG9LIHMDLLM@MGEDBMHNLCLD@LDL@ODIKHOCDCMDCKOGEHKBDEHK2.IHFHKILFKDBDGM@LKDBDODCLMKHGLNIIHKMEKHFMDEGCGM@MGCOCN@LGDLM,EKB@M@LIDBEB2.@DD@OD@KDCNBDCLNLBDIMAMMH@LDODKDEHKFHEF@@K@DMD@DDLK@KDDLDDKDMLEHNGCG#&HEMDDLM,EKB@GIHIN@MHGDKDMLEHKFHEF@@K@LBHFFHG

EKD@MDK2.CODKLMFD@GLKD@MDKKDLLM@GBDMHGEDBMHGCHDD@B@ODLHED2.HBDGBHCGMDLDFHDBNDL@GC@ODDGHMDOHODCLMK@MDDLEHKGBKD@LGMDKCODKLM A@MDKG@MOD73,LIBGEHKD@FIDHKAMDDGDMBKDBHFAG@MHGFDB@GLFLNLDCMHCODKLE@GMAHCDL*5KDLNF@AMLLADB@NLDD@BMFD@GD2.FHDBNDL@CCDCMHMDKDIDKMHKDMD9BDLM@MKDBHGDLDEIDIMCDLG@LLHB@MHGMMDGD2.FHDBNDFNLMADDFG@MDCMHF@GM@GLDEMHDK@GBD9DDFG@MHGHEMDLD9BDLHNCBHNGMDK@BMMD@CO@GM@DHE@CCGMDGD2.FHDBND9NLMDGNFADKHE2.FHDBNDLDDIKDLLF@KDIKDLDGM@A@@GBDADMDDGMD@CO@GM@DLHEIKDLDGMG@CDCODKLMHEEHKDGIDIMCDLMH9BDL@@GLMMDCL@CO@GM@DLHEKDLMKBMGMD9BDKDIDKMHKD

$ 2HDBN@K-HHHEMD.D$KCDC<

\8 2. $ 4 IDIMCDACGBDEM 2." 9 Q"" \ +L 2.# 9 "!Q$! \ +L L ? L

2." 9 B@G ` FBKHHANG FBKHHANG * B@G 9 `? $ . I`? ' . \ 2."FHDBND '

2.# 9 B@G ` B@G * `?$I`? V ' \V 2."` B@G* V 2.# ''($'

\V 2.# 9 "!Q#! 2. \ B@G 4I@KM@@EEGM

IMMUNOLOGY : SELF DISCRIMINATION

20

8@B @BC

V L \ V . 8@B @BC !I V . \ V . ] 8@B @BC "8@@MDC BHIKHMDGL @GCBHIC . 8DBL GAMHKKDBDIMHK ` 8DBL 92 V 8DBL B 2@BKHI@DCDGCKMB BD3DNMKHI V \M V

./## . 8DB -BD V B 7 -BD . R

B > 8@B @BC @MDKG@MODI@M@ 8DKNFIKHMDG E@BMHK ` L@B @BC V .$BHGODKM@LD

\8V 8@B @BC ?

./%7@LLHB@MDCIKHMDG

./% VDDKMKHBMDL L. 2@BKHI@D 875@ V5@HBMHLL ?8DGDLBDGMDKMKHBMDL ./% 2@BKHI@D M

\V LDEF@KDK M *` .

"? R> L@B @BC !

V R> >

07` H R> ` M R> \ 07 \ R> ` V L

BHL@MHG ` ]B@KAHCK@MD + R> > ` V >? $@@BMHLD $ L@B @BC !V

07 ODLBD H ? R> M@@BMHLD L@B @BC ` ! V? * \V V ? R> L@B @BC . W V

3GDCHHL@BB@KCDL@KDIKHBDLLDCMGMDH@II@K@MNLG@GHKCDKDCLDJNDGBDHEKD@BMHGL9DEKLMFHCEB@MHGHEIKHMDGLCDLMGDCEHKLDBKDMHGHKEHKMDI@LF@FDFAK@GDLMDKDFHO@HEMKDD@CCMHG@F@GGHLDKDLCNDL9LLEHHDCAMDLDJNDGM@@CCMHGHE@G3@BDMNBHL@FGDMDKDFHO@HEMHFHKDF@GGHLDL@GCMD@CCMHGHE@ENBHLD @GCMHFHKD3@BDMNBHL@FGDL1G@MKDD@@BMHLD @GCMKDDL@B @BCKDLCNDL@KD@CCDC

8DGDLBDGBD,CO@GBG@DMDBHFIDHE@DGM@MDODGMN@D@CMHCD@M

8MHDGCDGMM LDEF@KDK \ V . 4 W M 9

F_/^5/JXc`aX/X_/Kc`aZ] aX`/^Zc`YZX]/_`_]Z/]X\/YZ`_Z/aXX/`c/ZX]Z XZ2/X_/XY_`c^X]/]/Z/]`/ZX]Z XZ/acZ`_/YX/`/Z_Z`_5/cX_`c^XZ`_5/`c/__2

F_/^5/JXc`aX/X_/Kc`aZ] aX`/^Zc`YZX]/_`_]Z/]X\/YZ`_Z/aXX/`c/ZX]Z XZ2/X_/XY_`c^X]/]/Z/]`/ZX]Z XZ/acZ`_/YX/`/Z_Z`_5/cX_`c^XZ`_5/`c/__2

IMMUNOLOGY : SELF DISCRIMINATION

21

4. Recognition of induced or altered self

V ` V V ` > V M > V V %M R`> > V M

> L -@BD@NMHGHFHNLFDB@GLF

\ V V I -DMK@BDN@K LG@CDKODCEKHFHMDKBDL

- \ 9 V ` V 57 73@LD I@M@ /3,C@F@D V 9 I&$CDIDGCDGMI@M@ > V > V +

\ 9V ` V > V\. V4 V 73BD 5 9 V

R> 2."` . 3BD` ./9BD\. FDHCBD 3#/@BMO@MGKDBDIMHK ]

3#/ 92 ,5! 8MKHLGDG@LDL @BMO@MHGI@M@ L @C@IMHK + 9 85" 85#MKHLGDIHLI@M@LDL R 3BD > V @BMO@MGKDBDIMHK GAMHKKDBDIMHK VV M ENCDBLHGF@G > + M

T 5/OD6:569

5/JFD5/IEM

/aZYZ]Z/`//Xc/]]/`/\Z]]Z_/Y/KH/]]/a_/`_//YX]X_/`//]ZX_ `c/XZXZ_/X_/Z_ZYZ`c/ca`c7/Z//ZZ`_/^X\Z_/^X_Z^/Xc/^`c/cZX_//`/cc`c/X_/Zc5/X]]/`c/_`_/ac`7

/aZYZ]Z/`//Xc/]]/`/\Z]]Z_/Y/KH/]]/a_/`_//YX]X_/`//]ZX_ `c/XZXZ_/X_/Z_ZYZ`c/ca`c7/Z//ZZ`_/^X\Z_/^X_Z^/Xc/^`c/cZX_//`/cc`c/X_/Zc5/X]]/`c/_`_/ac`7

,BMHGHEI&$

CMIDI&$LKDJNKDCEHKAHMBDBBD@KKDLM@GC@IHIMHLLGCNBDCA/3,C@F@D

\885 *

IMMUNOLOGY : INNATE IMMUNITY

22

13HKF@D@MBDLBHGLMMNMODDIKDLLF@KDKLHELDEBDG@DGAMHKKDBDIMHKLHGMDDEEDBMHKBDLHEMDFFNGDLLMDF

GEDBMDCMK@GLEHKFDCHKC@F@DCBDLCHGKDN@MDMDDIKDLLHGHEMDLDF@KDKL@GCGCNBDMDDIKDLLHGHE@GCL EHK@BMO@MGKDBDIMHKLHG3@GCHMDKDEEDBMHK BDL

,IHIMHMBHKLDGDLBDGMBDLCLI@F@KDKLM@MM@MDFEHKI@HBMHLL AF@BKHI@DLDKD@LGDBKHMBBDLDIKDLLLG@LM@MGCNBDMLLNDKDI@KKDLIHGLDL,IIKHIK@MDDIKDLLHGHEMDLDF@KDKLDG@ADLBDLHEMDGG@MDFFNGDLLMDFMHCLBKFG@MDADMDDGGHKF@D@MBDL@GCGHGLDE @AGHKF@BDL@GCMHGHKDI@HBMHLDHKMDF@LGDDCDC

8DECLBKFG@MHG;8/@GDKMDHK

W VV \ * 8DEGHGLDECLBKFG@MHG WL `\ B * \M$ M 1 * + 2DAHNKGD H 2@BE@K@GD-NKGDM9"$"&$"` LM V M 5W "'! 5DMDK-2DC@@K9` * I \ W LFFNGHHB@8NKODK@GBD@LMD@C5KDLL8CGD"! L

\V \ 93VW V W 5@N2@GDK "% 42@GDK 59HDK@GBDC@GDK@GCMDDMDGCDCE@F,GGN@7DODHEFFNGHH "#""!%&"%WL * V < WL C@GDK L ] I $ @GMAHCBHK<

. 8DECLBKFG@MHG` /@GDKMDHK B 8DECLBKFG@MHG D B % <B > /@GDKMDHK + > 8DECLBKFG@MHG \ V .` \V LDE B + \R /@GDKLG@ W + . *

IMMUNOLOGY : ADAPTIVE IMMUNITY

23

IV. Self discrimination of Adaptive immunity

W M W \ 4 > *

R "!! $ V\ "! * \ $ "!! $ .4 \ .4 $ \ $ B $ 7

$ V .4 \. a $ 4 \.\ 4\V *

B * B ! \ B \ 4* ` * < "!B

W . .+ < D > \ /3, < W LDE \ > B * ` + M M

R W M > 5 9BD 9 -BD 9 R 5> > \*

5HLMODLDDBMHG

3D@MODLDDBMHG

\* $ ` $ 4 BW \* 9 \ M V M 7 V H

M B M \* IHLMODLDDBMHG V \* 3D@MODLDDBMHG M 7 V \ ` . 4 . M 9-BD V ` > \ M ` + M VB M M 3 + *` +

9BDF@MNK@MHGG9FNL

9BD W \ 9BD W 9BDDIDK9BD./%9FIHBMD` BMHMB9 BD

‘9’ ‘-’

> W \ V 9FNL - ‘9’ 9BD R-HGDF@KKH > M V -BD .

*

V MV +

2. LDEIDIMCD+ > 8NKOO@LG@ M * M

\` 8NKOO@LG@ =*

W W B M \B 5 + V R .\V W < D * \V 5 \ VB M V %$ \ \ RL V . 4 + \ + -9BD H . $ VR . LNKOO@LG@ \ V 9 LNKOO@LG@ + VR 2. IDIMCD LNKOO@LG@+ LNKOO@LG@ > V VW L L B V ` 7\* < V W* ] L*

B LNKOO@LG@ D 7 *

W > D \B W + LG@ < ` >

IMMUNOLOGY : T CELL MATURATION

24

W ;W ./% DIDK9BDDIDK9BD W

,BMO@MHGHE9BD

,BMO@MHGHE-BD

,BMO@MHGHE2@BKHI@D

GE@FF@MHG

DIDK9BD > M -BD ?M > V + LBMHMB 9BD DIDK9BD > + 2@BKHI@D DIDK9BD .D13K ] W

W ;+ DIDK9BD` ;+BMHMB 9BD 7

R \ 8 I \+ 9FIHBMD9K@GG L \* 9BD * $ ` 9BD` `

8HF@MBKDBHFAG@MHG

DIKDLLHGHE9.7DGD

BDIKHEDK@MHG

@GMDGGCNBDCLDDBMHG3D@MOD5HLMOD

@BJNLMHGHEF@MNKDIDGHMIDL@GCENGBMHG@B@I@AMDL

V ` -V F@MNK@MHG`` .\V 9V ` -V 2. IDIMCD +

8HF@MBKDBHFAG@MHG

W > M W !4` \. ` \

^^

9FNL B*

9.7 =*

2.,GMAHC ` $ 9BD 9BDKDBDIMHK .9BD,5. \ > M .9.7 ,5. 2. \ +L * M 2. \ 2. +L >

-BD .FFNGHHANG 9BD 9.7 ` . . ?L 9K@GLFDFAK@GD R> BR -BD LHNADEHKF @GMAHC L

N a . .B \ > .MFNLON@KL` V !V \

IMMUNOLOGY : SOMATIC RECOMBINATION

25

9.79BDKDBDIMHK R> B@G` B@G B@G` B@G R> *;@K@ADI@KM; .HGLDKODCI@KM. \. \8 B 9.7 M V V ` ./$ . V R> H

M 9.7 9BD ] ,5. L \ > B 9.7 \V M \ 9.7 M .4 ."KDIDKMHKD

V \8 Y 8HF@MBKDBHFAG@MHG $9.7 > L . B@G 9;.LDFDGM? LDFDGM VV . \ ` `? . B@GDGD 9 ;LDFDGM `? . B@GDGD 9 & ` LDFDGM ‘ B ` ’ * \8 LDFDGM VV . ` \V . ` LDFDGM B M ;

;/.9.7 B@G` D@OB@G 9B /LDFDGM 9BD` -BD 9FNL -HGDF@KKH `;/.LDFDGM M ` \ ` V 5 ;/.LDFDGM 5 V R . W /$ M

\V V 9.7 B M *-4&

6& 1N #FZ 7a=887Y]Z_\7\7`^8Z^^_`X_Z^XZ`_8Z_:7^]

. ;/KDBHFAG@LD * L* * * 7,"KDBHFAG@MHG@BMO@MGDGD"`7,#KDBHFAG@MHG@BMO@MGDGD# V * 7,"7,#

"9BD-BD . \ "!!!B 7 *

-BD 9 + ` & R> RHHI R ;/; V ; & W W ?;&"/#';' V -V L -V ; " . ` .DGDKDBHFAG@MHG + B &"#''(&"$!!#"!!!B

V . L ` WV ` WV \ $% \ $` \. L ` &!!B + "!!#!! %W L*. L ` + %W .4KDBDIMHKDCMG #!! \B ?+ .` .4 @GMAHCBHK<

IMMUNOLOGY : NEGATIVE SELECTION

26

BOX . 5 NEGATIVE SELECTIONBOX . 5 NEGATIVE SELECTION

. \ M 9BD .9.7` -BD .FFNGHHANG M;@K@ADI@KM 8HF@MBKDBHFAG@MHG /$ \V V \ . M

. \ R>` M* + ]V \V 9FNL -HGDF@KKH \ 8 7 M + V * L* 3D@MODLDDBMHG

\ ` V <WV + < \ 4B9BD 9 ,5. L * LDE2.# 2. .> \ M` 9BD +V * LDE2.# LDEIDIMCD " ‘’ MLDE2.# GHGLDE IDIMCD ‘’ GHGLDE M 9BD ‘’ M +L B M \. ` M # 5HLMODLDDBMHG

\V 2. +L M 7 ] \ V +L M < * \ V V /3, \* @IHIMHLL $

M 2.. W 2. M 89BD < L 2. M 9W M \V M N$ R M . . ?M W

". 4 * V IKHMDHLHFD . R> +L +L * +L . 2." L

,5. B +L * . 8 2.# L

. 4 V V ` * . L * M

4 >\V DIDK9BD V`,5. 2. * L . L \B > ` < `B >2. * . `B \. RDIDK9BD

#DIDK9BD ,5. 2.#B? .MHMB 9BD2."B ? 9.7 7 \ 9.7 ./%./ R> ./% 2.# .HGLDKODCI@KM M ./ 2." .HGLDKODCI@KMM 9.7 ? DIDK9BD ./%B 2.#BM BMHMB 9BD ./B 2."B M

\ IKDBNKLHK M 9BD DIDK9BD BMHMB 9BD *

\

/]]/^XcXZ`_/ "Z N 7a=887_YZ7_]^7_Z7`8Y``\8Y7ZB``]@Y``\]X]]@Y7Z77`Z`_Xcc^@cZ@Z^^7Z`_7;9:

IMMUNOLOGY : T CELL MATURATION

27

I `? \ 9.7 B@G . \ * B > *

,DBDBNLHG

W 5W 9BD 9.7B \V R LHF@MBKDBHFAG@MHG $. > . B@GDGD R . V 9 . ? R . @DBDBNLHG

\. B . ` 7 7 I `? . W

. B@GDGD$ ./%./* R B@G \ ./%./ * /HNADIHLMOD \ B@G 9.7

5HLMODLDDBMHG

* 9.7 R 5HLMODLDDBMHG $9FB BHKMD .DIMD@BD > 9BD ./% ./ * DIMD@BD L LDEIDIMCD2."BHFID LDEIDIMCD2.#BHFID* V 2.BHFID DIDK9BD./%9BD > BMHMB 9BD./9BD 2.# CHNADIHLMOD9BD ./%B *./ .\. 2.#B DIDK9BD

8DEIDIMCDLDE2.BHFID V LNKOO@LG@ 7 @IHIMHLL $

3D@MODLDDBMHG

B $ > V >B ‘ V’ 9BD BHKMD FDCN@ 3D@MODLDDBMHG $ V M@EEGMV a VB 9FNL W

IMMUNOLOGY : B CELL MATURATION

28

-BDF@MNK@MHGG-HGDF@KKH

9BD` > -BD R 9BD R -BD . . FFNGHHANGDGD@KK@GDFDGM $9.7DGD@KK@GDFDGM ` 7,"` 7,# D@OB@G MB@G ;;@K@ADI@KMHED@OB@G

` B -.7-BDKDBDIMHK9.7 ` 5HLMOD 3D@MODLDDBMHG \V 5HLMODLDDBMHG 9 9BD` M > B-.7 9 \ LNKOO@LG@ 3D@MODLDDBMHG 9BD \`. +L ` -BD R \V 9BD` -BD

\ KDBDIMHKDCMG"

-BDF@MNK@MHG

\8 Y -BD F@MNK@MHG` * DB ` 9BD` 3 ` M

"7DBDIMHKDCMG

R +L ` V ,IHIMHLL a B \ V 7,DGD L L -.7 . ` MB@G;KDBHFAG@MHG -.7 ` 9 \ V `> V -.7 7 9 R

W L . ` 5HLMOD 3D@MODLDDBMHG \ > ` R ` B * + 9 < ?V ‘’ ?$ 4

? WV DIDK9BD` .MHMB 9BD\. -BD \V W L DIDK9BD V DIDK9BD . *

IMMUNOLOGY : OUTLINE OF IMMUNITY

29

` > . W 5 5 5 ] WGG@MDFFNGM 5 B > * > W MW@C@IMODFFNGM 5 B 5 \ $ I W MW $ &' 9` V W WIKF@KFFNGDKDLIHGLD I $ \ WV WLDBHGC@KFFNGDKDLIHGLD W R \V L *`MW V 8 >V V MW ] L ` $> W \M $> 5 #$ MW \V B W 9 MW 5 W +

W

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IMMUNOLOGY : REFERRENCES

30

V. REFERRENCES

TEXT BOOK: Cellular and Molecular Immunology, Abul K. Abbas, 4th edition.

1. S.J. Simpson, P.J. Hines, Self-discrimination, a life and death issue, Science 296 (2002) 297-316

2. R.Medzhitov, C.A. Janeway Jr., Decoding the patterns of self and nonself by the innate immune system, Science 296 (2002) 298-300.

3.P.Matzinger, The Danger Model: a renewed sense of self, Science 296 (2002) 301-304

4.R.E. Langman, M.Cohn, If the immune repertoire evolved to be large, Cellular immunology 216(2002) 15-22

5.Bevan M. In thymic selection, peptide diversity gives and takes away, Immunity 7:175-178, 1997