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Ch27 The Immune System

Ch27 The Immune System. Yuki Juan NTU May 26, 2003. Outline. Introduction Antibody-based or humoral immunity Activation of B cells to produce antibodies T cells and cell-mediated immunity Why does the human immune system so fiercely reject foreign human cells Monoclonal antibodies.

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Ch27 The Immune System

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  1. Ch27 The Immune System Yuki Juan NTU May 26, 2003

  2. Outline • Introduction • Antibody-based or humoral immunity • Activation of B cells to produce antibodies • T cells and cell-mediated immunity • Why does the human immune system so fiercely reject foreign human cells • Monoclonal antibodies

  3. Outline • Introduction • Antibody-based or humoral immunity • Activation of B cells to produce antibodies • T cells and cell-mediated immunity • Why does the human immune system so fiercely reject foreign human cells • Monoclonal antibodies

  4. Terms • Autoimmune reactions: • The immune system would attack the components of the body • Autoimmune disease

  5. The Cells Involved In The Immune System • B cells: • Multiply and undergo their primary maturation in bone marrow • T cells: • Multiple and mature in thymus glands • Helper T cells and cytotoxic killer T cells

  6. Hemopoiesis

  7. Two Immune Protective Systems • Humoral immunity • Cell-mediated immunity

  8. Humoral Immunity • Antibody: • Combine with the foreign antigens • Antigen: • Antibody generation

  9. Cell-mediated Immunity • Cytotoxic T cells or killer T cells recognize abnormal cells in the body. • The killer cell attaches to the virus-infected cell and destroys it.

  10. The Differences Between Humoral And Cell-mediated Immunity • The humoral system: • is part of the defence against virus in the blood or in the mucous membrane before it infects a cell. • Cell-mediated immunity • Destroys the host cell after the latter has become infected and in doing so aborts virus replication in that cell.

  11. Outline • Introduction • Antibody-based or humoral immunity • Activation of B cells to produce antibodies • T cells and cell-mediated immunity • Why does the human immune system so fiercely reject foreign human cells • Monoclonal antibodies

  12. Antibodies • Immunoglobulins (Igs) • Y-shaped protein • Two identical light polypeptide chains • Two identical heavy chains

  13. Structure of Antibody

  14. Terms • Epitope • The specific part of the antigen which is recognized by an antibody • Clone • A collection of identical cells arising from multiplication of a single cell

  15. Different Classes of Antibodies • IgM • When the body responds to an antigen, the first produced antibody • Multi-subunit or polymeric • Form of antibody with 10 antigen combining sites • IgG • More prolonged challenge by the same antigen • IgA • Of importance as a first of defence

  16. Generation Of Antiboy Diversity • 300 V gene fragments • 4 J gene segments • C gene segment

  17. The Process of Rearrangment Leading to a Functional L Chain Immunoglobulin Gene

  18. Outline • Introduction • Antibody-based or humoral immunity • Activation of B cells to produce antibodies • T cells and cell-mediated immunity • Why does the human immune system so fiercely reject foreign human cells • Monoclonal antibodies

  19. The Principle of Clonal Selection • Macfarlane Burnet

  20. Conversion of A Virgin B Cell to An Activated State, But not yet to an Antibody-producing Plasma Cell • MHC classes II proteins: on the surface of the B cells

  21. Comparison of Receptors on B and T Cells

  22. Activation of a Helper T Cell By An Antigen-presenting Cell (APC) Cell surface markers known as clusters of differentiation APC: A special phagocytic white cell

  23. A Helper T Cell Activating a B Cell to Become A Clone of Plasma Cells Secreting Antibody

  24. Summary Scheme of Antibody Production by B Cells

  25. Term • Memory cells • They are the basis of long-term immunity from a repeat infection

  26. Outline • Introduction • Antibody-based or humoral immunity • Activation of B cells to produce antibodies • T cells and cell-mediated immunity • Why does the human immune system so fiercely reject foreign human cells • Monoclonal antibodies

  27. Class II MHCs and Class I MHCs • Helper T cells • recognize displayed peptides on class II MHCs • Have CD4 proteins • Killer T cells • require display on class I MHCs • Have CD8 proteins

  28. Sequence of Events In Cell-mediated Immune Reaction to a Foreign Antigen Synthesized Inside Cells

  29. Outline • Introduction • Antibody-based or humoral immunity • Activation of B cells to produce antibodies • T cells and cell-mediated immunity • Why does the human immune system so fiercely reject foreign human cells • Monoclonal antibodies

  30. Why Does the Human Immune System So Fiercely Reject Foreign Human Cells • The main cause of rejection of foreign tissue grafts in the MHC molecules on cells.

  31. Outline • Introduction • Antibody-based or humoral immunity • Activation of B cells to produce antibodies • T cells and cell-mediated immunity • Why does the human immune system so fiercely reject foreign human cells • Monoclonal antibodies

  32. Monoclonal Antibodies • The achievement of this earned Cesar Milstein and Georges Kohler in Cambridge a Nobel Prize

  33. 單株抗體 • 由單一細胞株所製造出來的抗體

  34. 多株抗體 • 抗血清是多株抗體, 這些抗體是由各種不同種B細胞所產生抗體之混合物

  35. 單株抗體的特株性質 • 它只和抗原中的某種抗原決定位置結合,不會與不同之抗原決定位置相結合,所以有很高的專一性 • 它和抗原決定位置結合的強度及性質完全相同,所以容易用它來純化抗原

  36. 單株抗體的製造方法 • 正常細胞藉由轉型(transform)變成癌細胞;也就是使正常細胞表現出致癌基因(oncogene) • 如何使抗體分泌細胞變成癌細胞 • 用致癌物質或病毒使此類細胞內表現致癌基因 • 細胞融合技術 • 致癌細胞之致癌基因融合到抗體產分泌細胞中融合瘤細胞(hybridoma)

  37. 融合瘤細胞(Hybridoma)之製造 • 1975, Milstein and Kohler發表1984,諾貝爾生理醫學獎 • 老鼠的融合瘤細胞 脾臟B細胞 + 骨髓瘤細胞  以特殊溶液處理，分離融合細胞 篩選具有特殊抗體的細胞株 自該細胞的組織培養中，收集所需抗體

  38. 單株抗體的應用 • 檢驗試劑的開發製造 • 醫學治療 • 生技產品之純化 • 農業及畜牧業 • 基礎研究

  39. 單株抗體的應用-檢驗試劑的開發製造 • 荷爾蒙 • 組織及細胞抗原 • 藥物監控 • 藥物濫用 • 微生物 • 抗體及過敏原 • 酵素 • 生長因子

  40. 單株抗體的應用-醫學治療 • 器官移植 • 腫瘤影像 • 抗癌藥

  41. Ch 29 Gene Cloning, Recombinant DNA Technology, Genetic Engineering Yuki Juan NTU May 27, 2003

  42. Outline • The first step-cutting the DNA with restriction endonucleases • Gene cloning, or how genes are isolated • Isolation of a genomic clone of a human gene • Cloning a human cDNA • What can be done with the cloned DNA • Knockout mice of gene targeting

  43. Outline • The first step-cutting the DNA with restriction endonucleases • Gene cloning, or how genes are isolated • Isolation of a genomic clone of a human gene • Cloning a human cDNA • What can be done with the cloned DNA • Knockout mice of gene targeting

  44. DNases and Restriction Enzymes • DNases • The digestive enzymes of pancreatic juice • Cut the phosphodiester bonds • Cut DNA randomly • Restriction enzymes • Don’t cut DNA randomly • Each recognizes a specific short sequence of bases so as to make a cut at a precision point in the sequence

  45. 基因選殖 • 1970, Smith發現第二類核酸限切酵素，可以很準確分割DNA • 1973, Boyer-Cohen-Chang完成第一基因選殖的工作 The first to be isolated from E. coli strain R

  46. Outline • The first step-cutting the DNA with restriction endonucleases • Gene cloning, or how genes are isolated • Isolation of a genomic clone of a human gene • Cloning a human cDNA • What can be done with the cloned DNA • Knockout mice of gene targeting

  47. Clone • Refers to multiple identical copies produced from a single origin • Genomic cloning and cDNA cloning

  48. 寄主細胞 • 蛋白質表現系統主要有 • 大腸桿菌: 操作方便、便宜 • 缺點: • 沒有修飾蛋白質的能力 • 無法正確摺疊 • 會產生毒素 • 酵母菌 • 昆蟲細胞: 操作較複雜、成本高 • 哺乳類細胞: 操作較複雜、成本高

  49. Outline • The first step-cutting the DNA with restriction endonucleases • Gene cloning, or how genes are isolated • Isolation of a genomic clone of a human gene • Cloning a human cDNA • What can be done with the cloned DNA • Knockout mice of gene targeting

  50. 第二類核酸限切酵素 黏端(sticky end) 鈍端(blunt end)

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