1. Chapter 9

2. Introducion Introducion   Specific immune response cells   Non-specific immune response cells Immune cells  Immune cells ( T cell 、 B cell and APC ) (phagocyte,NK cell,  T cell and B1 cell)  Lymphocytes   T cell and B cell   NK cell

3. *heterogenicity ( 异质性 ) *ability for recognizing Ag (TCR / BCR) can induce specific immune response *heterogenicity ( 异质性 ) *ability for recognizing Ag (TCR / BCR) *can induce specific immune response T Lymphocytes and B Lymphocytes T Lymphocytes and B Lymphocytes Major cells participated in specific immune response Common characteristics

4.  Surface marker  Subsets and function  Development process of T cell in the thymus in the thymus

5. VV VV CC CC TCR  A.TCR ---Characteristic marker of all T cell and specific receptor of recognizing Ag   Structure ---heterodimer thatconsists of  chain and  chain (or  chain and  chain) linked by disulfide-bonds ---heterodimer that consists of  chain and  chain (or  chain and  chain) linked by disulfide-bonds B. CD3 molecule 1.TCR-CD3 complex Ⅰ.Surface marker of T cell (TCR  /TCR  ) or TCR    ---each chain consists of a V and a C region on the extramembrane region  Belong to members of IgSF ---each chain consists of a V and a C region on the extramembrane region ( , , ,  and  chain)

6. V  V  //  Common model TCR-CD3  (80%~90%) TCR-CD3   Function CD3:transmit activating signal TCR:only recognize antigen peptide-MHC complex ---made up of TCR and CD3 molecules C.TCR-CD3 complex ITAM

7. 2.CD4 and CD8 molecule A. Co-receptor of T cell 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 molecules ---CD28,CD2,LFA-1 and CD40L V VV V V VV V 22 CD8 + TCD4 + T

8. (B7.1/B7.2) (CD58) CD40L (LFA-2) CD40 (CD28-B7 最重要 ) CD40L- -CD40 →co-stimulatory signal of activation for B cell APC 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

9. 4. Mitogen receptor B.Mitogen binding to mitogen receptor →activation, proliferation and trans- →activation, proliferation and trans- formation of T cell formation of T cell PHA-receptor ( 植物血凝素受体 ) ConA- receptor ( 刀豆蛋白 A 受体 ) (lymphocyte transformation test) --- --- Various membrane molecules of recognizing mitogen on the surface of T cell A.Mitogen receptor

10. Ⅱ.Subsets and Function of T Cells 1.TCR  T cell ＆ TCR  T cell 2.CD4 + T cell ＆ CD8 + T cell 3.Th,Tc,Ts and T DTH cell 4.Naive T cell & memory T cell 5.NK1.1 + T cell

11. 1.TCR  T cell ＆ TCR  T cell 不同标志 TCR  + T 細胞 TCR  + T 細胞 分布分布分布分布 CD4 + 或 CD8 + CD4 -,CD8 - /CD8 + 60%~70% 5%~15% 外周淋巴组织 皮肤, 粘膜丰富 功 能 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

12. 2.CD4 + T cell ＆ CD8 + T cell 2.CD4 + T cell ＆ CD8 + T cell Common surface marker Recognize antigen ---only recognize antigen peptide- MHC complex ---CD2 + 、 CD3 + 、 TCR  +

13. A. CD4 + T cell (CD4 + CD8 - TCR  + )  Recognize antigen peptide  Subtype  Function ---consisits of 13~17 amino acid residue and restricted by MHC- Ⅱ molecules (help T cell and delayed type hypersensitivity T cell)Th and T DTH (help T cell and delayed type hypersensitivity T cell)Th1 and Th2 mediate immune response take part in immunoregulation activate M  and NK cell

14. Th0 Th1 Th2 CMIHI IL-2, IL-12 IL-4 IL-4,5,6, IL-10,13 IL-2, IL-12, IFN- , TNF Tc;T DTH B 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 )

15. B. CD8 + T cell (CD4 - CD8 + TCR  + ) (also called cytotoxic T lymphocyte, CTL/Tc)   Recognize Ag and cytotoxicity   Subtype   Function ---consisits of 8~10 amino acid residue and restricted by MHC- Ⅰ molecules Tc and TsTc 1 and Tc Tc and Ts Tc 1 and Tc 2 cytotoxicity cytotoxicity relate to graft rejection relate to graft rejection * kill target cells * mechanism:cytolysis and apoptosis Feature:  specifically  directly  repeatedly

16. 3.Th, Ts, Tc and T DTH cells A.Th and Ts cell B.Tc and T DTH 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)

17. 4.Naive T cell & memory T cell naive ( 初始 ) T cell activated T effector T (Tc,T DTH ) menory T Ag (CD45RA + ) ( CD45RO + ) 5.NK1. 1 + T cell (NK1.1 +, TCR-CD3 +,DN/CD4 + ) cytotoxicity immunoregulation (non-specific killing effects) (secrete IL-4,IFN-  )

18. Ⅲ. Development process of T cell in the thymus CD2 + CD5 + CD4 - CD8 - CD3  + (DN cell) → pT  +,TCR  + →preTCR CD2 + CD3 ＋ CD4 + CD8 +  + (DP cell) CD3 low, TCR  + IL-7,SCF IL-2,IL-4 mature T cell CD4 + / CD8 + ( SP cell) TCR-CD3 + 1. Development of TCR pro-T →→ →→ pre-T cell 2. Selection process selection process Positive selectionNegative selectionPositive selectionNegative selection

19. (DP) (SP) (DC/M  ) CD4 (95 %) pre-T MHC- Ⅰ MHC- Ⅱ pre-T pro-T (DN) pre-T 5% 自身肽

20.  Surface marker  Subsets and function  Development process of B cell in the bone marrow

21. A.BCR    Belong to prototype of IgSF  Membrane Ig (mIg) on the surface of B cell monomermature B cells express mIgM and mIgDcombine with specific antigenmonomermature B cells express mIgM and mIgDcombine with specific antigen 1.BCR complex Ⅰ.Surface marker of B cell characteristic marker specific receptor of recognizing antigen

22. BCR -Ig  /Ig  BCR -Ig  /Ig  ---consist of BCR and Ig  /Ig  Ag binding site  Function  Structure BCR (B cell receptor ) Ig  / Ig  ---combine with specific Ag signal transduction molecules *signal transduction molecules *take part in expression and transport of mIg chain transport of mIg chain B.BCR complex

23. A.Activatory co-receptor of B cell and costimulatory  Costimulatory molecule CD19, CD21(CR2) and CD81 CD40 binding to CD40L ( 为 B 细胞活化提供协同刺激信号 CD80/86 (B7.1/B7.2) binding to CD28 or CTLA-4 CD40 binding to CD40L ( 为 B 细胞活化提供协同刺激信号 ) CD80/86 (B7.1/B7.2) binding to CD28 or CTLA-4  Activatory co-receptor 2.Molecules participated in activation of B cell and IR molecule

24. A.CR1 (CD35) B.Complement receptor  CR1 is a immune adherent-receptor (IA-R)  also called C3bR or C3b/C4bR ---CR2 is C3dR and EBV-receptor on the surface of B cell B.CR2 (CD21) C.Other membrane molecules  CD22, CD20 and CD32  Mitogen receptor

25. Ⅱ.Subset and Function of B Cell 1.B1 cell (CD5 +,mIgM +,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: non-Ig class switch not produce immune memory polyreactivity non-Ig class switch not produce immune memory polyreactivity B.Function     anti-infection  eliminate changing autoantigen  induce autoimmune disease 2.B2 cell (CD5 -,mIgM +,mIgD + )

26. A.Major cells participated in IR B.Function   Participate in humoral immunity   Antigen presenting cell (APC)   Secrite CKs --- produce Abs of single specificity and high affinity ( presenting of processing peptide to T cell) (participate in immunoregulation)

27. Ⅲ.Development of B Cell Pro-B pre-B V-DJ 基因重排 Ig  +,Ig  + IL-7, SCF immature B  + pre-B-R + V-J 基因重排  +, L + (mIgM + ) mature B mIgM + mIgD + Ag self-tolerance Ag plasma cell plasma cell (product antibody) Bm pre-B-R + ---  H -  L ( 5/Vpre-B) 替代性 BCR 复合体 (  H-  L –Ig  / Ig  ) HH LL

28. 1.Common characteristics A.Origin and distribution B.Surface marker of NK cell   CD3 –, CD56 +, CD16 + ( Fc  R Ⅲ + ),CD57 ＋    CD2 +, LFA-1 +, TCR –, BCR –  Receptor of NK cells p84

29. KAR KIR ) (contain ITIM) (contain ITAM) (contain ITIM) MHC- Ⅰ molecules ligand polysaccharide MHC- Ⅰ molecules activatory signal inhibitory signal produce signal activatory signal inhibitory signal kill target cells loss of killer activity kill 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 )

30. 2.Biologic function of NK cell A.Anti-infection and anti-tumor B.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 mediate ADCC and release killer mediator of target cell → necrosis or apoptosis of cells mediate ADCC and release killer mediator