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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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