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Historical Perspective

Historical Perspective. Variolation A technique 1718, Lady Mary Wortley Montagu, dried crusts from smallpox to be inhaled into the nostrils or inserted into the skin Improved by Edward Jenner in 1798, fluid from a cowpox to be pustuled into people Louis Pasteur

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Historical Perspective

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  1. Historical Perspective • Variolation • A technique • 1718, Lady Mary Wortley Montagu, dried crusts from smallpox to be inhaled into the nostrils or inserted into the skin • Improved by Edward Jenner in 1798, fluid from a cowpox to be pustuled into people • Louis Pasteur • 1880, Succeeded in growing the bacterium throught to cause fowl cholera in culture • The attenuated pathogen would immunize and not cause disease, called vaccine

  2. The beginnings of the discipline of immunology • 1881, Pasteur, first vaccinated one group of sheep with heat-attenuated Bacillus anthracis • 1885, Pasteur, the first vaccine for human against rabid dog • 1890s, Emil von Behring and Shibasaburo Kitasato, first insight into the mechanism of immunity - serum

  3. Humoral and cellular immunity • Humoral immunity • 1930s, Elvin Kabat, gamma-globulin • The active molecules in immunoglobulin fraction, antibodies, contained in body fluid • Cellular immunity • 1883, Elie Metchnikoff, observe phagocytes • Cell-mediated immunity • 1950s, lymphocytes, the cell responsible for both cellular and humoral immunity

  4. Early immunity theories • Selective theory • Interaction between an infectious agent and a cell-bound side-chain receptor would result in release of the side chain and would induce the cell to produce and secrete more side-chain receptor with the same specificity • 1950, clonal-selection theory • Instructional theory • Antigen played a central role in determining the specificity of the antibody molecule.

  5. The Nature of Immunity- Immunity was originally used to indicate exemption from taxes and this meaning still exits in the term "diplomatic immunity". 免疫系統保護人體免於受病源體侵入。 免疫反應可分為應變性（adaptive immune response）及先天性（innate）或非應變性免疫反應（non-adaptive immune response) 專一性（specificity）、記憶性（memory）及自我辨識（self-discrimination）為應變性免疫反應主要特徵。

  6. Innate immunity –resistance mechanisms are not specific to a particular pathogen

  7. Adaptive immunity-a high degree of specificity as well as the remarkable memory property • Antigenic specificity • To distinguish subtle difference among antigens • Diversity • To recognize billions of uniquely different structures on foreign antigens • Immunologic memory • A second encounter with the same antigen induces a heightened state of immune reactivity • Self/nonself recognition • To respond only to foreign antigens

  8. Response of immune system • 專一性（specificit）： • 對外來物之間化學性質微小的不同具有顯著的辨識能力。 • 記憶性（memory）： • 受外來物質感染後，能演變出對外來物特性的記憶，此種特性可能可以持續一生。 • 個體受感染後，先後產生免疫反應稱為primary response及secondary response，經過此免疫反應後，個體會產生具有記憶性的細胞，進而對相同之病源體產生記憶性之對抗。 • 自我辨識（self-discrimination）： • 如器官移植或輸血時產生的排斥現象。

  9. Cells of the immune system- 專一性及非專一性辨識細胞組成。 • 吞噬細胞： • 單核吞噬細胞（單核球，mononuclear phagocyte）：進入組織發育成巨噬細胞（macrophage）。 • 多形核嗜中性細胞（嗜中性球，polymorphonuclear neutrophil，PMN）：白血球之一種。 • 淋巴球細胞： • B細胞（B lymphocyte） • T細胞（T lymphocyte）：T-helper Cell（TH）、T-cytotoxic Cell（TC） • 大顆粒淋巴球（large granular lymphocyte，LGL）：natural killer cell（NK）。

  10. 毒殺性細胞（cytotoxic cell） • 多形核嗜酸性細胞（嗜酸性球，polymorphonuclear eosinophil）：白血球之一種。 • 嗜鹼性細胞（嗜鹼性球，basophil）：白血球之一種。 • 肥大細胞（mast cell） • 血小板（platelet） • 輔助細胞（auxiliary cells）

  11. Soluble mediators of immunity- 調理素（opsonin）進行調理作用（opsonization） • 補體蛋白質（complements）： • 血清蛋白，調節吞噬作用、控制發炎反應、與抗體相互作用參與免疫防禦（專一性防禦）。 • 細胞激素（cytokines）： • 免疫反應進行時，傳遞各細胞間訊息的一群大分子，稱之。 • 為蛋白質、或醣蛋白，如干擾素（interferons，INFs）、間白素（interlukins，ILs）、株落刺激因子（colony stimulating factors，CSFs）、腫瘤壞死因子（tumor necrosis factors，TNF）及轉型生長因子（transforming growth factor，TGF）。 • 抗體（antibodies，immunoglobulins）

  12. Biological events of immune system 免疫系統中的事件： recognition of the target pathogen effective defence against the pathogen Recognition unit： 如抗體分子、TCR（T細胞表面受體，T Cell Receptor）。 Defence unit： 如T細胞、mast cell或其他具有抗體受器之免疫細胞。 形式： Combined recognition and defence unit：僅具有單一辨識特異性，如T細胞的作用。 Separate recognition and defence unit：具有多種不同的辨識特異性，如免疫球蛋白的作用。

  13. Immunological recognition 抗原的辨認是所有應變性免疫反應的基礎。 抗原與少數可以辨認它的細胞結合後，可誘導細胞迅速增殖，即抗原能選擇對本身產生專一結合之細胞株落，此種過程稱之為株落選擇（colonal selection）。 • Antibodies（immunoglobulins）：與抗原結合之作用。 • 抗原：可以誘導B細胞產生抗體之分子or可被應變性免疫系統中之組成細胞專一性辨識之分子。 • 抗原決定部位（epitope）：抗原與抗體結合之特定部位。

  14. T lymphocytes • 細胞受感染會將病源體之一小段蛋白表現在細胞表面上，T細胞就能辨認出來。 • 將抗原片段表現出來的細胞稱之為抗原呈獻細胞（antigen presenting cell，APC）。 位於抗原呈獻細胞表面，用來呈獻抗原片段的分子稱為主組織相容復合體（major histocompatibility complex，MHC）。

  15. Immunological defence-Lysis or digestion：the successful elimination of pathogens • 中和作用（neutralization） • 吞噬作用（phagocytosis） • 毒殺作用（cytotoxic reaction） • 細胞自殺作用（apoptosis）

  16. Inflammation • 受感染部位血流量增加。 • 微血管通透性增加，使原無法通過的大分子通過內皮細胞，使免疫反應之可溶性物質到達感染部位。 • 白血球離開微血管進入周圍組織 – Influx of phagocytes

  17. 趨化作用（chemotaxis）藉由白血球表面分子(L-selectin)與活化之內皮細胞(P- and E- selectin)間的交互作用，使細胞向感染部位移動的作用。 • 細胞遷移作用：margination（selectin-mediated，integrin-mediated） and extravasation (diapedesis)。

  18. Immunopathology 自體免疫（autoimmunity） 過敏（hypersensitivity） 免疫不全（immunodeficiency）

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