Chapter 9Chapter 9

IntroducionIntroducion

Specific immune response cells

Non-specific immune response cells

Immune cellsImmune cells

(( T cell T cell 、、 B cell and APC )B cell and APC )

(phagocyte,NK cell,(phagocyte,NK cell,T cell and B1 cell)T cell and B1 cell)

LymphocytesLymphocytes

T cell and B cell NK cell

*heterogenicity *heterogenicity (( 异质性异质性 )) *ability for recognizing Ag (*ability for recognizing Ag (TCR / BCTCR / BCR)R) *can induce specific immucan induce specific immune responsene response

T Lymphocytes and B LymphocytesT Lymphocytes and B Lymphocytes

•• Major cells participated in specific immune response•• Common characteristics

Surface markerSurface markerSubsets and function Subsets and function Development process of T cell Development process of T cell in the thymusin the thymus

VV

CC

TCR

A.TCRA.TCR---Characteristic marker of all T cell and specific receptor of recognizing Ag

Structure---heterodimer that---heterodimer that consists of consists of chain chain and and chain (or chain (or chain and chain and chain) li chain) linked by disulfide-bondsnked by disulfide-bonds

B. CD3 moleculeB. CD3 molecule

1.TCR-CD3 complex1.TCR-CD3 complexⅠⅠ.Surface marker of T cell.Surface marker of T cell

(TCR/TCR)

or TCR

Belong to members of IgSF ---each chain consists of a V and a ---each chain consists of a V and a C region on the extramembrane regioC region on the extramembrane regionn ( ,,, and chain)

VV V V

/

Common modelCommon model ••TCR-CD3(80%~90%)••TCR-CD3 FunctionFunction• • CD3:transmit activating signal •• TCR:only recognize antigen peptide-MHC complex

---made up of TCR and CD3 molecules C.TCR-CD3 complexC.TCR-CD3 complex

ITAM

2.CD4 and CD8 molecule2.CD4 and CD8 moleculeA. Co-receptor of T cell A. Co-receptor of T cell B. Function B. Function enhance adhension of T cell with APC or target cell( 靶细胞 )

participate in signal transduction

T cell

APC靶细胞

3.Costimulating signal molecules3.Costimulating signal molecules ---CD28,CD2,LFA-1 and CD40L

V V V V

2

CD8+T CD4+T

(B7.1/B7.2)

(CD58)

CD40L(LFA-2)

CD40

(CD28-B7 最重要 )

• • CD40L- -CD40 →co-stimulatory signal of activation for B cell

APCAPC

• • CTLA-4--B7.1/B7.2→suppressive signal for activative T cell

3.Co-stimulating signal molecules

•• CD28,CD2 and LFA-1 binding to ligand on the surface of APC →costimulating signal of activation for T Cell

4. Mitogen receptor4. Mitogen receptor

B.Mitogen binding to mitogen receptor B.Mitogen binding to mitogen receptor → →activation, proliferation and trans-activation, proliferation and trans- formation of T cellformation of T cell

PHA-receptor PHA-receptor (( 植物血凝素受体植物血凝素受体 ))

ConA- receptor ConA- receptor (( 刀豆蛋白刀豆蛋白 AA 受体受体 ) )

(lymphocyte transformation test)

--- --- Various membrane molecules of recognizing mitogen on the surface of T cell

A.Mitogen receptorA.Mitogen receptor

ⅡⅡ.Subsets and .Subsets and Function Function of T of T CellsCells1.TCR1.TCR T cell T cell ＆＆ TCRTCR T cell T cell

2.CD42.CD4++T cell T cell ＆ ＆ CD8CD8++T cell T cell

3.Th,Tc,Ts and T3.Th,Tc,Ts and TDTHDTH cell cell

4.Naive T cell & memory T cell4.Naive T cell & memory T cell

5.NK1.15.NK1.1++ T cell T cell

1.TCR1.TCR T cell T cell ＆ ＆ TCRTCR T cell T cell

不同标志不同标志TCR+T 細胞 TCR+ T 細胞

分布分布

CD4+ 或 CD8+ CD4-,CD8-/CD8+

60%~70% 5%~15% 外周淋巴组织 皮肤 , 粘膜丰富

功 能功 能 参与 IR 的主要亚群 非特异性杀伤 ( 抗胞内感染 , 抗肿瘤)

Th CTL CTL, TCR T

p85

外周血 组织

TCR 多样性 极高 低识别抗原 8~17 个氨基酸 简单多肽 / 脂类 /HSP/多糖

2.2.CD4CD4++T cell T cell ＆ ＆ CD8CD8++T cellT cell

Common surface markerCommon surface marker

Recognize antigenRecognize antigen

---only recognize antigen peptide- MHC complex

---CD2+ 、 CD3+ 、 TCR+

A. CD4A. CD4++T cell T cell (CD4(CD4++CD8CD8--TCRTCR++))Recognize antigen peptideRecognize antigen peptide

SubtypeSubtype

FunctionFunction

---consisits of 13~17 amino acid residue and restricted by MHC- moleculesⅡ

••Th and TDTH (he(he

lp T cell and delayed type hypersensitivity T cell)lp T cell and delayed type hypersensitivity T cell) ••Th1 and Th2

•• mediate immune response• • take part in immunoregulation• • activate M and NK cell

Th0

Th1 Th2

CMI HI

IL-2, IL

-12IL-4

IL-4 ,5,6 ,IL-10,13

IL-2, IL-12, IFN-, TNF

Tc;TDTHB cell

IL-10

IFN-

Ag

+ +

--- 参与细胞免疫 ,介导细胞毒及迟发型超敏性炎症

--- 参与体液免疫 (辅助 B 细胞产生抗体 )

B. CD8B. CD8++T cellT cell (CD4(CD4--CD8CD8+ +

TCRTCR++))(also called cytotoxic T lymphocyte, CTL/Tc) Recognize Ag and cytotoxicity

Subtype

Function

---consisits of 8~10 amino acid residue and r---consisits of 8~10 amino acid residue and restricted by MHC- moleculesⅠestricted by MHC- moleculesⅠ

•• Tc and TsTc and Ts •• Tc 1 and TcTc 1 and Tc 2

•• cytotoxicity cytotoxicity

•• relate to graft rejectionrelate to graft rejection

*kill target cells*mechanism:cytolysis and apoptosis

Feature: specifically directly repeatedly

3.Th 3.Th ,,Ts Ts ,,Tc and TTc and TDTHDTH cellscells

A.Th and Ts cellA.Th and Ts cell

B.Tc and TB.Tc and TDTHDTH cell cell

CD4+T 细胞和 CD8+

T 细胞既是效应性 T 细胞 ,又是调节性细胞

( 介导 DTH, 引起炎症反应 )

( 抑制免疫应答 )

(effector T cells)

(regulatory T cell)

4.Naive T cell & memory T 4.Naive T cell & memory T cellcell naivenaive(( 初始初始 ) ) T cellT cell

activated Teffector T (Tc,TDTH)menory Tmenory T

Ag(CD45RA(CD45RA++))

((CD45ROCD45RO+ + ))

5.NK15.NK1..11++ T cell T cell(NK1.1+, TCR-CD3+,DN/CD4+ )

cytotoxicityimmunoregulation

(non-specific killing effects)(non-specific killing effects)

(secrete IL-4,IFN-(secrete IL-4,IFN-))

ⅢⅢ. Development process . Development process of T cell in the thymus of T cell in the thymus

CD2+CD5+ CD4- CD8-

CD3+ (DN cell) pT

+,TCR+→→preTCR

CD2+ CD3 ＋ CD4+ CD8+

+ (DP cell) CD3low, TCR+

IL-7,SCF IL-2,IL-4

mature T cellCD4+/ CD8+( SP cell) TCR-CD3+

1. 1. DevelopmentDevelopment of TCR of TCR

pro-T →→ →→ pre-T cellpro-T →→ →→ pre-T cell

2. Selection process2. Selection process

selection p

rocesselection

proces

ss

••Positive selection Positive selection ••Negative selectionNegative selection

(DP) (SP)

(DC/M)

CD4

(95%)

pre-Tpre-TMHC-Ⅰ

MHC-Ⅱ

pre-Tpre-T

pro-Tpro-T(DN)

pre-Tpre-T

5%

自身肽

Surface marker Surface marker Subsets and fSubsets and functionunction DevDevelopment process of B cell in the boelopment process of B cell in the bone marrowne marrow

A.BCRA.BCR

Belong to prototype of IgSF Membrane Ig (mIg) on the surface of B cell

••monomer monomer ••mature B cells express mIgMmature B cells express mIgM and mIgD and mIgD ••ccombine with specific antigen ombine with specific antigen

1.BCR complex1.BCR complex

ⅠⅠ.Surface marker of B cell.Surface marker of B cell

characteristic marker specific receptor of recognizing antigen

BCR -IgBCR -Ig/Ig/Ig

---consist of BCR and Ig/Ig

Ag binding site FunctionFunctionStructureStructure

•BCR (B cell receptor )

•Ig / Ig ---combine with specific Ag---combine with specific Ag

*signal transduction moleculessignal transduction molecules*take part in expression and *take part in expression and transport of mIg chaintransport of mIg chain

B.BCR complexB.BCR complex

A.Activatory co-receptor of B cell and coA.Activatory co-receptor of B cell and costimulatorystimulatory

Costimulatory moleculeCostimulatory moleculeCD19, CD21(CR2) and CD81CD19, CD21(CR2) and CD81

•• CD40 binding to CD40L CD40 binding to CD40L ((为为 BB 细胞活化提供协同刺激信号细胞活化提供协同刺激信号 )

•• CD80/86 (B7.1/B7.2) CD80/86 (B7.1/B7.2) binding to CD28 or CTLA-4 binding to CD28 or CTLA-4

Activatory co-receptorActivatory co-receptor

2.Molecules participated in 2.Molecules participated in activation of B cell and IR activation of B cell and IR

moleculemolecule

A.CR1 (CD35)A.CR1 (CD35)

B.Complement receptorB.Complement receptor

CR1 is a immune adherent-receptorCR1 is a immune adherent-receptor(IA-R)(IA-R) also calledalso called C3bR or C3b/C4bRC3bR or C3b/C4bR

---CR2 is C3dR and EBV-receptor on the ---CR2 is C3dR and EBV-receptor on the surface of B cellsurface of B cell

B.CR2 (CD21)B.CR2 (CD21)

C.Other membrane C.Other membrane moleculesmolecules CD22, CD20 and CD32CD22, CD20 and CD32 Mitogen receptorMitogen receptor

ⅡⅡ.Subset and Function of B Cell.Subset and Function of B Cell1.B1 cell1.B1 cell (CD5(CD5++,mIgM,mIgM++,mIgD,mIgD--))A.Belong to non-specific immunocyte Ag→ →body → Ab 细菌多糖 低亲和力 IgM变性自身 Ag ( 包括自身抗体 )

Feature:Feature:• • non-Ig class switch non-Ig class switch • • not produce immunot produce immune memory ne memory • • polyreactivity polyreactivity

B.FunctionB.Function anti-infection eliminate changing autoantigen induce autoimmune disease 2.B2 cell2.B2 cell (CD5(CD5--,mIgM,mIgM++,mIgD,mIgD++))

2.B2 cell2.B2 cell (CD5(CD5--,mIgM,mIgM++,mIgD,mIgD++))

A.Major cells participated in IRA.Major cells participated in IR B.FunctionB.Function Participate in humoral immunity

Antigen presenting cell (APC)

Secrite CKs

------produce Abs of single specificity and produce Abs of single specificity and high affinityhigh affinity

((presenting of processing peptide to T cell)presenting of processing peptide to T cell)

(participate in immunoregulation) (participate in immunoregulation)

ⅢⅢ.Development of B Cell.Development of B CellPro-B Pro-B

pre-Bpre-B

V-DJ 基因重排 Ig+,Ig+

IL-7, SCF

immature Bimmature B

+ pre-B-R+ V-J 基因重排

+ , L+

(mIgM+)

mature Bmature B mIgM+ mIgD+

Ag Ag

self-toleranceself-tolerance

Ag Ag plasma cellplasma cell(product antibody)(product antibody)

BmBm

pre-B-R+

--- H -L

( 5/Vpre-B)

替代性 BCR 复合体 (H-L –Ig

/ Ig )

HL

1.Common characteristics1.Common characteristicsA.Origin and distributionA.Origin and distribution B.Surface marker of NK cellB.Surface marker of NK cellCD3– , CD56+, CD16+( FcRⅢ+ ) ,CD57 ＋ CD2+, LFA-1+, TCR–, BCR–

Receptor of NK cells

p84

KAR KIRKAR KIR(contain ITAM) (contain ITIM)) (contain ITIM)

ligand polysaccharide MHC- molecules ⅠMHC- molecules Ⅰ produce signal activatory signal inhibitory signal activatory signal inhibitory signal

kill target cells loss of killer activitykill target cells loss of killer activity ( 病毒感染细胞 / 肿瘤细胞 ) ( 自身组织细胞不被破坏 )

( 占主导 )

2.Biologic function of NK cell2.Biologic function of NK cellA.Anti-infection and anti-tumorA.Anti-infection and anti-tumor

B.Participate in immunoregulationB.Participate in immunoregulation

kill target cells---natural killer activity

mechanism

(secrete IFN-,IL-1,GM-CSF)

•• AM of NK cell binding to corresponding ligand AM of NK cell binding to corresponding ligand

of target cell → necrosis or apoptosis of cells of target cell → necrosis or apoptosis of cells

•• mediate Amediate ADCC andDCC and release killer mediatorrelease killer mediator