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Lymphocyte

Chapter 9. Lymphocyte. 淋巴细胞. Introducion. Immune cells.  Specific immune response cells  Non-specific immune response cells. ( T cell 、 B cell and APC ). (phagocyte,NK cell, T cell and B1 cell).  Lymphocytes.  T cell and B cell  NK cell. T Lymphocytes and B Lymphocytes.

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Lymphocyte

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  1. Chapter 9 Lymphocyte 淋巴细胞

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

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

  4. T lymphocyte T淋巴细胞 • Surface marker • Subsets and function • Development process of T cell in the thymus

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

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

  7. 2.CD4 and CD8 molecule A. Co-receptor of T cell B. Function T cell CD8+T CD4+T enhance adhension of T cell with APC or target cell(靶细胞) participate in signaltransduction V V V V 2 靶细胞 APC 3.Costimulating signal molecules ---CD28,CD2,LFA-1 and CD40L

  8. 3.Co-stimulating signal molecules (LFA-2) CD40L CD40 (B7.1/B7.2) (CD58) APC (CD28-B7最重要) •CD28,CD2 and LFA-1 binding to ligand on the surface of APC →costimulating signal of activation for T Cell • CD40L- -CD40 →co-stimulatory signal of activation for B cell • CTLA-4--B7.1/B7.2→suppressive signal for activative T cell

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

  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 TDTH cell 4.Naive T cell & memory T cell 5.NK1.1+ T cell

  11. 1.TCR T cell ＆ TCR T cell TCR+T細胞TCR+ T細胞 p85 不同标志 CD4+或CD8+ CD4-,CD8-/CD8+ 60%~70% 5%~15% 外周淋巴组织 皮肤,粘膜丰富 外周血 组织 分布 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 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

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

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

  14. Ag Th0 IL-10 IL-2, IL-12 IFN-  IL-4 Th2 Th1 IL-4 ,5,6 , IL-10,13 IL-2, IL-12, IFN-, TNF B cell Tc;TDTH + + CMI HI ---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-Ⅰmolecules •Tc and Ts•Tc 1 and Tc 2 Feature: specifically directly repeatedly • cytotoxicity • relate to graft rejection *kill target cells *mechanism:cytolysis and apoptosis

  16. 3.Th ,Ts ,Tc and TDTHcells (抑制免疫应答) A.Th and Ts cell B.Tc and TDTH cell (regulatory T cell) (介导 DTH, 引起炎症反应) (effector T cells) CD4+T细胞和CD8+T细胞既是效应性T细胞,又是调节性细胞

  17. 4.Naive T cell & memory T cell naive(初始)T cell (CD45RA+) Ag effector T (Tc,TDTH) activated T menory T (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 1. Development of TCR IL-7,SCF IL-2,IL-4 pro-T →→ →→ pre-T cell selection process CD2+CD5+ CD4- CD8- CD3+ (DN cell) pT+,TCR+→preTCR CD2+ CD3＋CD4+ CD8+ + (DP cell) CD3low, TCR+ 2. Selection process mature T cell •Positive selection •Negative selection CD4+/ CD8+(SP cell) TCR-CD3+

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

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

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

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

  23. 2.Molecules participated in activation of B cell and IR A.Activatory co-receptor of B cell and costimulatory molecule Activatory co-receptor CD19, CD21(CR2) and CD81 Costimulatory molecule •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

  24. B.Complement receptor A.CR1 (CD35) CR1 is a immune adherent-receptor(IA-R)also calledC3bR or C3b/C4bR B.CR2 (CD21) ---CR2 is C3dR and EBV-receptor on the surface of B cell 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 B.Function anti-infection  eliminate changing autoantigen induce autoimmune disease 2.B2 cell(CD5-,mIgM+,mIgD+)

  26. 2.B2 cell(CD5-,mIgM+,mIgD+) 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 Ag Pro-B plasma cell (product antibody) mature B V-DJ基因重排Ig+,Ig+ mIgM+ mIgD+ Bm IL-7, SCF L pre-B H + pre-B-R+ V-J基因重排 pre-B-R+ --- H -L (  5/Vpre-B) immature B 替代性BCR复合体(H-L –Ig/Ig) + , L+ (mIgM+) Ag self-tolerance

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

  29. KAR KIR (contain ITAM) (contain ITIM) ligand polysaccharide MHC-Ⅰmolecules produce signal activatory signal inhibitory signal (占主导) 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)

  30. 2.Biologic function of NK cell A.Anti-infection and anti-tumor B.Participate in immunoregulation kill target cells---natural killer activity mechanism •AM of NK cell binding to corresponding ligand of target cell → necrosis or apoptosis of cells •mediate ADCC andrelease killer mediator (secrete IFN-,IL-1,GM-CSF)

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