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Chapter 6 Immunocytes

Chapter 6 Immunocytes. Xu Qin. Immune cells. Specific immune response cells ( T cell ， B cell and APC )  Non-specific immune response cells ( phagocyte ， NK cell, NKT cell ， Neutrophils ， Macrophages and Mast cells ). Origin and Differentiation of Immunocytes.

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Chapter 6 Immunocytes

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  1. Chapter 6 Immunocytes Xu Qin

  2. Immune cells • Specific immune response cells ( T cell，B cell and APC ) Non-specific immune response cells ( phagocyte，NK cell,NKT cell， Neutrophils， Macrophages and Mast cells )

  3. Origin and Differentiation of Immunocytes Lymphoid stem cells pluripotent stem cell myeloid stem cell RBC platelet Neutrophils DC Mast cell T cell NK cell Macrophage

  4. Section 1 T Lymphocyte （T 淋巴细胞）

  5. Surface marker • Subsets and function • Development process of T cells

  6. Surface marker of T cell • TCR-CD3 complex • CD4 and CD8 molecule • CD28 and CTLA-4 • ICOS • LFA-1 & LFA-2 • CD40L • ICAM-1

  7. Subsets of T cell  Development Stages • naive T cells • effector T cells • memory T cells  TCR types • TCRαβ+ & γδ+  CD4+T cell ＆ CD8+T cell

  8. Subsets of T cell  Functions of T cells • helper T cells • effector T cells • cytotoxic T cells • delayed T cells • naive T cells • regulatory T cells • memory T cells • suppressor T cells

  9. Development process of T cell • positive selection:double-positive cells (CD4+/CD8+) • CD4+/CD8- MHCII • CD4-/CD8+ MHC I • Negative selection : • Thymocytes interact too strongly with MHC molecules die • The remaining cells exit the thymus as mature naive T cells

  10. Naive T cell • A naive T cell is considered mature • havenot encountered antigen in the peripheryyet

  11. Memory T cell • antigen-specific T cells • persists long-term after an infection has resolved • quickly expand to large numbers of effector Tcells upon re-exposure to their cognate antigen

  12. Helper T cell • have no cytotoxic or phagocytic activity • Th0 cells differentiate into Th1 or Th2 cells depending on cytokine environment • IFN-γ drives Th1 cell production • IL-4 drives Th2 cell production • IL-17 drives Th17 cell production • Th1: Maximizes the killing efficacy of the macrophages, CD4+ • Th2: Stimulates B cells into proliferation, CD4+

  13. Effector T cell • release cytokines：IL-2, IFN-γ

  14. Cytotoxic T cell (Tc) • express the CD8 glycoprotein at their surface, CD8+ • recognize their targets by MHC I • kill the target cells without antigen

  15. Regulatory T cell (Treg) • formerly known as suppressor T cells • CD4+ • antigenplay a role in the suppression of immune responses

  16. Section 2 B Lymphocyte （B 淋巴细胞）

  17. Development process of B cells • Surface marker • Subsets and function

  18. Development of B Cell Ag Pro-B plasma cell (product antibody) mature B V-DJ基因重排Ig+,Ig+ mIgM+ mIgD+ Bm high affinity Positive selection IL-7, SCF pre-B + 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 Negative selection

  19. Surface marker of B cell • BCR complex • characteristic marker • specific receptor of recognizing antigen • structure consist of BCR and Ig/Ig

  20. Subsets of B cell  B-1 cell  B-2 cell  Memory B cell

  21. B-1 cell  Belong to non-specific immunocyte polyreactivity  Subtypes • B-1a (CD5+) • B-1b (CD5-) • Function • anti-infection • eliminate changing autoantigen • induce autoimmune disease

  22. B-2 cell  conventional B cells  Major cells participated in IR  Function • Produce Abs of single specificity and high affinity • Antigen presenting cell (APC) • Secrete CKs(participate in immunoregulation)

  23. Memory B cell  formed from activated B cells that are specific to the antigen  able to live for a long time • can respond quickly following a second exposure to the same antigen

  24. Section 3 Innate immune cells （固有免疫细胞）

  25. Innate immune cell • Natural killer cell • Mast cell • Eosinophil • Basophil • Phagocytic cells • Macrophages • Neutrophils • Dendritic cells

  26. Chapter 7 Surface markers on T, B lymphocytes Xu Qin

  27. Section 1 Surface markers on T lymphocytes （T 淋巴细胞表面分子）

  28. Molecules on T lymphocytes surface 1. CD molecules associated with T cell recognition, adhesion and activation Common CD molecules T cell

  29. 1.TCR-CD3 complex TCR (TCR/TCR) characteristic marker of all T cell specific receptor of recognizing Ag • structure • heterodimer that consists of  chain and  chain (or  chain and  chain) • linked by disulfide-bonds • each chain consists of a V and a C region CD3 molecule ( ,,,  and  chain)

  30. 1.TCR-CD3 complex TCR-CD3 complex ---made up of TCR and CD3 molecules • function • CD3, transmit activating signal • TCR,only recognize antigen peptide – MHC complex

  31. TCR-CD3 complex TCR specifically recognizes peptides presented on MHC molecules CD3 transduces the signal 1 of T cell activation

  32. 2. CD4 and CD8 molecule • Co-receptor of T cell • Function • enhance adhension of T cell with APC or target cell • participate in signal transduction

  33. 2. CD4 and CD8 molecule CD4 is mainly expressed on mature Th cells, macrophages and DC. It is HIV receptor. It binds the nonpolymorphic region of MHC-II CD8 is mainly expressed on mature Tc cells and binds the nonpolymorphic region of MHC-I

  34. 3. Costimulatory signal molecules • TCR-CD3 complex provides signal 1 • Costimulatouy signal or signal 2

  35. Main accessory molecules between T cells and APC

  36. 3. Costimulatory signal molecules CD28 CTLA-4 ICOS PD-1 CD40L CD2 LFA-1 and ICAM-1

  37. 4. Mitogen receptors and other receptors Mitogen receptors Other receptors

  38. Section 2 Surface markers on B lymphocytes （B 淋巴细胞表面分子）

  39. BCR complex • Structure ---consist of mIg and Ig/Ig • characteristic marker • specific receptor of recognizing antigen

  40. BCR complex • mIg • monomer • mature B cells express mIgM and mIgD • combine with specific antigen Ig / Ig • signal transduction molecules

  41. Molecules participated in activation of B cell •  Activatory co-receptor • CD19, CD21(CR2) and CD81 • Costimulatory molecule • CD40 binding to CD40L • CD80/86, binding to CD28 or CTLA-4 • Other membrane molecules • CD22, CD20 and CD32 • Mitogen receptor

  42. V1 V2 V3 Vn D1 D2D3 Dn J1 J2 J3 J4 Cm Cd Cg CeCa Germline Gene structure of BCR 4 types of gene segments • Heavy chain: V、D、J、C • Light chain：V、J、C V基因片断 D基因片断 J基因片断 C区基因 V区基因

  43. V1 V2 V3 VnD1 D2D3 DnJ1 J2 J3 J4 Cm Cd Cg CeCa V1V2 D2 J3 J4 Cm Cd Cg CeCa V1 V2 D2 J3 J4 Cm Cd Cg CeCa V2D2J3 J4 Cm Cd J4 V2D2J3 Cm Cd L VH Cm V2 D2 J3 Cm Germline Gene Rearrangement Rearranged BCR RNA transcript mRNA splicing Mature mRNA Pre peptide

  44. DH-JH连接 VH-DH-JH连接 Vκ-Jκ连接 Vλ -Jλ连接 only one allele of a gene is expressed while the other allele is silenced Alletic exclusion 等位排斥 Construct a functional gene with C gene Isotype exclusion 同种型排斥 Either κ or λ light chain is expressed by a B cell

  45. Generation of antibody diversity Combinational diversity 3.5 x 106 Junctional diversity increase >100 times Nucleotide Addition increase >2000 times Somatic hypermutation increase >1000 times

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