相關閱讀資料
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第一部分：單細胞生物發育出的防禦機制發展
Part I: Defense Mechanisms Developed by Unicellular Organisms
生物為了防禦，從原核生物便開始發展出辨識及移除病原體的各種機制。辨識機制可能源自病原體帶有特殊外源標記或是病原體缺乏與該生物相同的自我標記。因此，病原體辨識機制和自我/非自我的辨別能力便是依此演化出來。
To protect themselves, organisms, starting from prokaryotes, have developed mechanisms for the recognition and elimination of pathogens. Recognition mechanisms can be based on either the presence of distinctive foreign markers or by the absence of "self" markers. Accordingly, mechanisms of pathogen recognition as well as self/non-self discrimination have evolved.
第二部分：轉變為多細胞生物體導致細胞特化
Part II: The Transition to Multi-Cellularity Resulted in Cell Specialization
許多單細胞生物的防衛機制，在多細胞生物的所有細胞中保留下來，而其他機制僅存在於特化的細胞。轉變為多細胞後，不只要辨識病原，還要能辨識如癌細胞等因病變而改變的自身細胞，，因此演化出能辨識與移除外來侵入者，以及能與自身細胞共存的特化免疫細胞。
Many protective mechanisms of unicellular organisms were preserved in all cells of multi-cellular organisms, whereas others were preserved only in specialized cells. The transition to multi-cellularity necessitated not only recognition of pathogens but also recognition of an organism's own cells altered by pathological processes, such as cancer. Immune cells specialized in recognition and elimination of foreign invaders and compromised self-cells have evolved.
第三部分：演化上的里程碑 適應性免疫系統的起源
Part III: An Evolutionary Milestone: The Origin of an Adaptive Immune System
所有之前討論的機制（通常稱為先天性免疫）都源自於基因體中已編碼的病原辨識受體。大約四億五千萬年到四億七千萬年前，脊椎動物發展出一套全新的病原辨識系統，此系統靠著能製造出無數種不同受體，以及具特定受體的細胞株分裂增生，以因應抗原及病原體的挑戰，此機制使生物得以辨識與防衛各式各樣的抗原及病原體。
All previously discussed mechanisms (often called "innate immunity") are based on pathogen-recognizing receptors encoded in the genome. About 450-470 million years ago, vertebrates developed a new system of pathogen recognition. This system is based on the creation of unlimited variability of immune receptors and on clonal expansion of cells bearing a specific receptor in response to an antigen/pathogen challenge. This mechanism allows for recognition and protection against unlimited variety of antigens/pathogens.
| 週 | 課程單元 | 概述 | 閱讀資料 |
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| 1 | 講師與學生介紹 Introduction of Instructor and Students 課程概要與課程大綱討論 Overview and Discussion of the Syllabus 課程目標 Aim of the Course 如何閱讀科學論文 How to Read a Scientific Paper 文獻與資料庫搜尋 Literature and Database Searching 介紹下週主題 Introduction to Next Week's Topic |
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| 第一部分 單細胞生物的防禦機制發展 Part I: Defense Mechanisms Developed by Unicellular Organisms |
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| 2 | 辨識外來核酸 Recognition of Foreign Nucleic Acids 限制／修飾系統 The Restriction/Modification (R-M) System |
概述：細菌的限制/修飾系統會將缺乏自身標記特徵的視為病原體。宿主DNA中有甲基化的特定序列不會被分解，而無甲基化的外源DNA將被限制脢摧毀。此系統可能源於細菌的DNA錯誤配對修復系統，它同樣是以DNA的甲基化程度作為辨識依據。這種以DNA甲基化作為自身與異己的辨識原則的方式，成功的演化出來；因此，脊椎動物免疫細胞即以細菌DNA之甲基化形式作為辨識細菌的依據。 The restriction/modification (R-M) system of bacteria recognizes the absence of self as a feature of a pathogen. Host DNA is protected from digestion by methylation at specific sequences, while non-methylated foreign DNA is destroyed by restriction enzymes. This system possibly originated from the bacterial mismatch repair system, which is also based on recognition of the degree of DNA methylation. The principle of recognition of DNA methylation as a means of self/non-self discrimination was successful throughout evolution; thus immune cells of vertebrates recognize methylation patterns of bacterial DNA as non-self. |
Meselson, M., 與 R. Yuan.〈大腸桿菌的DNA限制脢〉，《自然》第217期 (1968年)，1110頁-1114頁。 Meselson, M., and R. Yuan. "DNA restriction enzyme from E. coli." Nature 217 (1968): 1110-4. Hemmi, H., O. Takeuchi, T. Kawai, T. Kaisho, S. Sato, H. Sanjo, M. Matsumoto, K. Hoshino, H. Wagner, K. Takeda, 與S. Akira.〈辨識細菌DNA的類Toll受體〉，《自然》第408期 (2000年)，740頁-745頁。 Hemmi, H., O. Takeuchi, T. Kawai, T. Kaisho, S. Sato, H. Sanjo, M. Matsumoto, K. Hoshino, H. Wagner, K. Takeda, and S. Akira. "A Toll-like receptor recognizes bacterial DNA." Nature 408 (2000): 740-5. |
| 3 | 辨識外源核酸 Recognition of Foreign Nucleic Acids 干擾RNA RNAi |
概述：另一種對病原核酸的防衛機制為干擾RNA。此辨識雙股RNA的機制從單細胞真核生物到哺乳動物中均有。 Another protective mechanism against pathogenic nucleic acids is RNA interference. It is conserved from unicellular eukaryotes to mammals and is based on recognition of double-stranded RNA. |
Hamilton, A. J., 與D. C. Baulcombe.〈植物中一種反義RNA在轉錄後期造成的基因默化現象〉，《科學》第286卷，1999年，950頁-952頁。 Hamilton, A. J., and D. C. Baulcombe. "A species of small antisense RNA in posttranscriptional gene silencing in plants." Science 286 (1999): 950-2. Li, H., W. X. Li, 與S. W. Ding.〈一種動物病毒對RNA默化的促進及抑制〉，《科學》第296卷(2002年)，1319頁-1321頁 Li, H., W. X. Li, and S. W. Ding. "Induction and suppression of RNA silencing by an animal virus." Science 296 (2002): 1319-21. 建議閱讀 Recommended Reading Plasterk, R. H.〈RNA默化：基因體的免疫系統〉，《科學》第296卷 (2002年)，1263頁-1268頁 Plasterk, R. H. "RNA silencing: the genome's immune system." Science 296 (2002): 1263-5. |
| 4 | 抗微生物胜肽 Anti-Microbial Peptides |
概述：抗微生物胜肽在所有動物門均可發現，扮演防衛微生物的重要角色。抗微生物胜肽以微生物細胞膜的一項特徵-細胞膜外側的帶負電分子為目標，即。雖然這些胜肽的種類繁多（已知有九百種），但它們都具有基本結構原則-"雙重性"（即疏水性和帶正電的胺基酸基團位於同一分子上的不同位置）在演化過程中被保留下來。演化關係遙遠的阿米巴原蟲的阿米巴孔道胜肽和哺乳動物的顆粒溶菌脢被認為有同源性。但此種相同的分子構造也可能是趨同演化的結果。 Anti-microbial peptides are found throughout all phyla and play a fundamental role in anti-microbial protection. Anti-microbial peptides target a distinctive feature of microbial membranes, namely, negatively charged molecules on the membranes' outer sides. Despite the great variety of these peptides (about 900 known), their fundamental structural principle known as an 'amphipathic' design (clusters of hydrophobic and cationic amino acids organized in discrete sectors) has been maintained in evolution. Such evolutionary distant anti-microbial peptides as amoebapores of amoeba and mammalian granulysins are thought to be homologous. The same design might also have originated by convergent evolution. |
Lemaitre, B., J. M. Reichhart, 與 J. A. Hoffmann. （果蠅宿主防衛：被屬於多種不同類型之微生物感染後，會誘發不同的抗微生物胜肽基因），《美國國家科學院院誌》第94卷 (1997年)，14614頁-14619頁。 Lemaitre, B., J. M. Reichhart, and J. A. Hoffmann. "Drosophila host defense: differential induction of antimicrobial peptide genes after infection by various classes of microorganisms." Proc Natl Acad Sci USA 94 (1997): 14614-9. Stenger, S., D. A. Hanson, R. Teitelbaum, P. Dewan, K. R. Niazi, C. J. Froelich, T. Ganz, S. Thoma-Uszynski, A. Melian, C. Bogdan, S. A. Porcelli, B. R. Bloom, A. M. Krensky, 與 R. L. Modlin.〈顆粒溶菌脢調節胞蝕型T細胞的抗微生物活性〉，《科學》，第282卷 (1998年)，121頁-125頁。 Stenger, S., D. A. Hanson, R. Teitelbaum, P. Dewan, K. R. Niazi, C. J. Froelich, T. Ganz, S. Thoma-Uszynski, A. Melian, C. Bogdan, S. A. Porcelli, B. R. Bloom, A. M. Krensky, and R. L. Modlin. "An antimicrobial activity of cytolytic T cells mediated by granulysin." Science 282 (1998):121-5. 建議閱讀 Recommended Reading Zasloff, M.〈多細胞生物的抗微生物胜肽〉，《自然》第415卷 (2002年)，389頁-395頁。 Zasloff, M. "Antimicrobial peptides of multicellular organisms." Nature 415 (2002): 389-95. |
| 5 | 利他性死亡 Altruistic Death |
概述：利他性死亡可視為趨同演化的一個例子，細菌與真核細胞獨自發展出在感染細胞中設陷捕捉病原體的機制。當細胞死亡時，同時殺死細胞內的病原體而使其餘細胞族群受益。在細菌中，此機制稱為中斷感染系統（Abi）。 Altruistic death can be regarded as an example of convergent evolution, where bacteria and eukaryotic cells independently developed a mechanism of trapping a pathogen inside the infected cell. As a result, the cell dies, killing the pathogen inside and thereby benefiting the rest of the cell population. 在多細胞生物中，感染細胞可進行程式化細胞死亡，或稱細胞凋亡。 In bacteria, this mechanism is known as abortive infection system (Abi). In multi-cellular organisms, an infected cell can undergo programmed cell death or apoptosis. |
Bouchard, J. D., E. Dion, F. Bissonnette, 與 S. Moineau.〈雙構造的噬菌體感染中斷機制AbiT：以Lactococcus lactis為例〉，《細菌學期刊》，第184卷 (2002年)，6325頁-6332頁。 Bouchard, J. D., E. Dion, F. Bissonnette, and S. Moineau. "Characterization of the two-component abortive phage infection mechanism AbiT from Lactococcus lactis." J Bacteriol 184 (2002): 6325-32. Tollefson, A. E., T. W. Hermiston, D. L. Lichtenstein, C. F. Colle, R. A. Tripp, T. Dimitrov, K. Toth, C. E. Wells, P. C. Doherty, 與W. S. Wold.〈Fas強制降解會抑制腺病毒感染細胞的凋亡〉，《自然》第392卷 (1998年)，726頁-730頁。 Tollefson, A. E., T. W. Hermiston, D. L. Lichtenstein, C. F. Colle, R. A. Tripp, T. Dimitrov, K. Toth, C. E. Wells, P. C. Doherty, and W. S. Wold. "Forced degradation of Fas inhibits apoptosis in adenovirus-infected cells." Nature 392 (1998): 726-30. 建議閱讀 Recommended Reading Raff, M.〈寫給入門者有關細胞自殺〉，《自然》，第396卷 (1998年)，119頁-122頁。 Raff, M. "Cell suicide for beginners." Nature 396 (1998): 119-22. |
| 第二部分 多細胞的轉變導致細胞特化 Part II: The Transition to Multi-Cellularity Resulted in Cell Specialization |
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| 6 | 多細胞生物如何辨識病原體？ How are pathogens recognized by multi-cellular organisms? 模式辨認與缺乏自我標記 Pattern Recognition and Missing Self |
偵測病原體的兩種方式－辨識病原體標記與辨識是否"缺乏自我標記"在多細胞生物中演化出更為複雜的模式。 The two principles of detecting pathogens, by recognition of pathogen markers or by recognition of "missing self", have evolved to greater complexity in multi-cellular organisms. 許多受體演化出辨識微生物病原之特定分子的機制，如巨噬細胞上的甘露糖結合受體能辨識格蘭氏陽性菌、陰性菌及真菌。由於阿米巴原蟲亦使用甘露糖受體來辨識細菌，顯示此種結合甘露糖的方式在演化過程中被保留下來。 Many receptors have evolved for recognizing conserved molecular patterns characteristic of microbial pathogens, e.g. macrophage mannose-binding receptor recognizes gram- positive and negative bacteria and fungi. Mannose-binding was preserved in evolution, since phagotrophic amoebae also use mannose receptors to recognize bacteria. 為了辨識"缺乏自我標記"的病原體，生物體中的所有細胞會表現某特定的分子作為標記，之後檢查每個細胞是否有此標記存在，任何缺乏此標記的細胞都將被摧毀。 To recognize a pathogen as "missing-self", the organism marks its own cells by expressing specific molecule/s and then screening all cells for the presence of this tag. Any cell that has failed the screen is destroyed. |
Ezekowitz, R. A., M. Kuhlman, J. E. Groopman, 與 R. A. Byrn.（一種人類血清中甘露糖結合蛋白在體外會抑制人類免疫不全症病毒之感染），《實驗醫學期刊》，第169卷 (1989年)，185頁-196頁。 Ezekowitz, R. A., M. Kuhlman, J. E. Groopman, and R. A. Byrn. "A human serum mannose-binding protein inhibits in vitro infection by the human immunodeficiency virus." J Exp Med 169 (1989): 185-96. Stern, P., M. Gidlund, A. Orn, 與 H. Wigzell. （自然殺手細胞溶蝕缺乏MHC之胚胎上皮組織癌細胞），《自然》第285卷 (1980年)，341頁-342頁。 Stern, P., M. Gidlund, A. Orn, and H. Wigzell. "Natural killer cells mediate lysis of embryonal carcinoma cells lacking MHC." Nature 285 (1980): 341-2. 建議閱讀 Recommended Reading Medzhitov, R., 與 C. A. Janeway, Jr.（先天性免疫系統解析自我及非我模式），《科學》第296卷 (2002年)，298頁-300頁。 Medzhitov, R., and C. A. Janeway, Jr. "Decoding the patterns of self and non-self by the innate immune system." Science 296 (2002): 298-300. |
| 7 | 多細胞生物如何摧毀病原體 How do multi-cellular organisms destroy pathogens? 吞噬作用 Phagocytosis |
概述：單細胞生物發展出吞噬作用作為攝食機制。多細胞生物將此機制轉為防衛內部與外來的病原體。特化的吞噬細胞現身再演化最早的中生動物－海綿。在較高等的生物中，更演化出數種不同的吞噬細胞。 Unicellular organisms developed phagocytosis as a trophic mechanism. Multi-cellular organisms transformed this mechanism into protection against endogenous and exogenous pathogens. Specialized phagocytes appear in sponges, the evolutionary oldest metazoan. In higher organisms several phagocytosing cell types evolved. |
Tsukano, H., F. Kura, S. Inoue, S. Sato, H. Izumiya, T. Yasuda, 與 H. Watanabe.〈Yersinia pseudotuberculosis經由抑制液泡上氫離子-ATP水解脢來阻斷B10.A老鼠巨噬細胞中吞噬體的酸化作用），《微生物病理學》第27卷 (1999)，253頁-263頁。 Tsukano, H., F. Kura, S. Inoue, S. Sato, H. Izumiya, T. Yasuda, and H. Watanabe. "Yersinia pseudotuberculosis blocks the phagosomal acidification of B10.A mouse macrophages through the inhibition of vacuolar H(+)-ATPase activity." Microb Pathog 27 (1999): 253-63. Hayashi, F., T. K. Means, 與 A. D. Luster.（類Toll受體刺激人體嗜中性球的功能），《血液》第102卷 (2003年)，2660頁-2669頁。 Hayashi, F., T. K. Means, and A. D. Luster. "Toll-like receptors stimulate human neutrophil function." Blood 102 (2003): 2660-9. 建議閱讀 Recommended Reading Niedergang, F., 與 P. Chavrier.（吞噬作用中的訊息傳遞與細胞膜的動態反應：殊途而同歸於吞噬體），《細胞生物學當代評論》第16卷 (2004年)，422頁-428頁。 Niedergang, F., and P. Chavrier. "Signaling and membrane dynamics during phagocytosis: many roads lead to the phagos(R)ome." Curr Opin Cell Biol 16 (2004): 422-8. |
| 8 | 多細胞生物如何摧毀病原體 How do multi-cellular organisms destroy pathogens? 補體與高反應性氧 Complement and Reactive Oxygen |
概述：多細胞生物不僅保留單細胞生物發展出的防衛機制，更發展出新的機制來防衛病原體。後口動物採用一種胜肽的階梯式反應系統，能摧毀細菌及其他生物的細胞膜。此種胜肽階梯式反應系統在不同生物群中演化出不同機制。在無脊椎動物中，此系統僅包含少數幾種胜肽，而在哺乳動物中，此系統約有三十種蛋白質參與補體階梯式反應，且此反應受到嚴密的調控。多細胞生物中的特化免疫細胞亦使用（除了抗微生物胜肽外）具有高反應性的氧化物，如帶電氧分子、過氧化氫及一氧化氮來殺死病原體。 Multi-cellular organisms retained the use of defense mechanisms developed in unicellular organisms and also developed new ones. Deuterostomia introduced a cascade system of peptides, which destroy not only bacterial but other membranes as well. This peptide cascade has evolved differently in disparate groups. In invertebrates, such systems consist of a few peptides, whereas in mammals, there are about 30 proteins involved in the complement cascade, and it is highly regulated. In multi-cellular organisms, specialized immune cells have also introduced the use (in addition to anti-microbial peptides) of reactive oxygen species, such as O2-, H2O2, and NO to kill pathogens. |
Kotwal, G. J., S. N. Isaacs, R. McKenzie, M. M. Frank, 與 B. Moss.（牛痘病毒的主要分泌蛋白抑制補體的階梯式反應），《科學》第250卷 (1990年)，827頁-830頁。 Kotwal, G. J., S. N. Isaacs, R. McKenzie, M. M. Frank, and B. Moss. "Inhibition of the complement cascade by the major secretory protein of vaccinia virus." Science 250 (1990): 827-30. Singhrao, S. K., J. W. Neal, N. K. Rushmere, B. P. Morgan, 與 P. Gasque.（補體自發性典型途徑的活化及細胞膜調節蛋白的缺失引發人類神經對補體溶蝕反應的感受性），《美國病理學期刊》第157卷 (2000年)，905頁-918頁。 Singhrao, S. K., J. W. Neal, N. K. Rushmere, B. P. Morgan, and P. Gasque. "Spontaneous classical pathway activation and deficiency of membrane regulators render human neurons susceptible to complement lysis." Am J Pathol 157 (2000): 905-18. 建議閱讀 Recommended Reading Nappi, A. J., E. Vass, F. Frey,與Y. Carton.〈一氧化氮與果蠅免疫的關聯〉，《一氧化氮》第四卷 (2000年)，423頁-430頁。 Nappi, A. J., E. Vass, F. Frey, and Y. Carton. "Nitric oxide involvement in Drosophila immunity." Nitric Oxide 4 (2000): 423-30. |
| 第三部分：演化上的里程碑 適應性免疫的起源 Part III: An Evolutionary Milestone: The Origin of an Adaptive Immune System |
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| 9 | 適應性免疫系統的受體 Receptors of the Adaptive Immune System 主要組織相容性複體(MHC)參概述：適應性免疫系統的受體源自屬於免疫球蛋白家族的先生性免疫受體。帶有受體蛋白基因的多片段序列，可能是由基因複製演化而來。在基因體中，這些基因分為數個片段，可以隨機組合成各式各樣的受體。這些在體細胞組合好的受體基因可能再因突變或轉換而有更多變化。一般認為蛋白質重組的表現，是由於細菌基因的轉位子被納入脊椎動物基因體中。適應性免疫顯示免疫的演化進入一個全新階段，對外源分子（抗原）的辨識以及自身標記（MHC）的機制合而為一。適應性免疫的T細胞僅會辨識與抗原表現細胞之主要組織相容性複體（MHC I 和 II）結合的外來抗原。 Receptors of the adaptive immune system originated from the innate immune receptors of the immunoglobulin super-family. Multiple genes that have likely evolved by gene duplication encode these receptors. In the genome, they are represented by several fragments, which can randomly rearrange to create a enormous number of diverse receptors. These receptors can be further diversified somatically by mutations and gene conversion. Proteins performing the rearrangement are thought to be bacterial transposons that became integrated into vertebrate genome. Adaptive immunity represents a new level of the evolution of immune system, where recognition of a foreign molecule (antigen) and "self" markers (MHC) are combined in one mechanism. T cells of the adaptive immune system recognize foreign antigens only in association with molecules of the Major Histocompatibility Complex (MHCI and II), which are expressed on the surface of antigen presenting cells. |
Hozumi, N., 與利根川進 〈免疫球蛋白基因之可變區與固定區之基因於體細胞內重組的證據〉，《美國國家科學院院誌》第73卷 (1976年)，3628頁-3632頁（譯註：利根川進 Susumu Tonegawa獨得1987年諾貝爾生理醫學獎，此篇即為得獎的關鍵論文。利根川進目前於麻省理工學院擔任教授，並主持Picower學習與記憶研究中心。） Hozumi, N., and S. Tonegawa. "Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions." PNAS 73 (1976): 3628-32. Kovacsovics-Bankowski, M. 與 K. Clark （巨噬細胞的主要組織相容性複體I會呈現經由吞噬作用而來的外來抗原），《美國國家科學院院誌》第90卷 (1993年)，4942頁-4946頁 Kovacsovics-Bankowski, M., and K. Clark, et al. "Efficient major histocompatibility complex class I presentation of exogenous antigen upon phagocytosis by macrophages." PNAS 90 (1993): 4942-6. |
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| 10 | 細胞株篩選與免疫記憶 Clonal Selection and Immunological Memory |
概述：適應性免疫系統受體的多樣化與細胞株篩選結合，增加了免疫反應的效率。對抗原的記憶存於生物體免疫細胞的不同株細胞裡，而非固定編碼存於基因體中。所以，終其一生，適應性免疫都能對繁多不同的新抗原做出反應。 The extensive variability of receptors of the adaptive immune system in combination with clonal selection improves the efficiency of an immune response. The memory of an antigen gets encoded in the clonal composition of the organism's immune cells instead of being conservatively encoded in the genome. Then, adaptive immunity is capable of responding to an unlimited variety of new antigens throughout the life course of the organism. |
Jerne, N. K., 與 P. Avegno.〈動物中特定免疫反應時血清的不活化吞噬性質〉，《免疫學期刊》第76卷 (1956年)，200頁-205頁。 Jerne, N. K., and P. Avegno. "The development of the phage-inactivating properties of serum during the course of specific immunization of an animal." J Immunol 76 (1956): 200-5. Burnet, F. M.（以細胞株篩選概念對Jerne的抗體產生理論做修正），《臨床醫師癌症期刊》第26卷 (1976年)，119頁-121頁。 Burnet, F. M. "A modification of Jerne's theory of antibody production using the concept of clonal selection." CA Cancer J Clin 26 (1976): 119-21. 林納．鮑林(Burnet, F. M)，〈一種抗體的結構與形成過程之理論〉，《美國化學學會刊》第62卷 (1940年)，2643頁-2657頁。 Pauling, L. "A Theory of the Structure and Process of Formation of Antibodies." J Am Chem Soc 62 (1940): 2643-57. |
| 11 | 適應性免疫系統如何與先天性免疫系統互動 How does the adaptive immune system interact with the innate immune system? |
概述：適應性免疫系統源自先天性免疫系統，而且在功能上也仰賴先天性免疫系統。適應性免疫系統的引入使脊椎動物的免疫系統擁有多變而複雜的結構，包含許多特化細胞和體液組成。有效的聯繫是此複雜系統正常運作的關鍵，因此，許多先天性及適應性免疫間的聯繫方式便演化出來。在此聯繫過程中，細胞激素扮演主要角色。 The adaptive immune system originated from the innate system and is functionally dependent on it. The introduction of adaptive mechanisms made the whole immune system of vertebrates a very diversified and complicated structure with many specialized cellular and humoral components. Effective communication is crucial for functioning of complex systems, thus many ways of communication between the innate and adaptive immune systems, as well as within them, have evolved. The major role in this communication is played by cytokines. |
Hsieh, C. S., .與 S. E. Macatonia等 （由李斯特菌誘發的巨噬細胞產生之IL-12影響TH1 CD4+ T細胞的發育），《科學》第260卷 (1993年)，547頁-549頁。 Hsieh, C. S., and S. E. Macatonia, et al. "Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages." Science 260 (1993): 547-9. Rimoldi, M., and M. Chieppa, 等 〈（腸道免疫衡定現象由上皮細胞與樹突細胞協調控制〉，《自然 免疫學》第六卷 (2005年)，507頁-514頁。 Rimoldi, M., and M. Chieppa, et al. "Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells." Nat Immunol 6 (2005): 507-514. 建議閱讀 Recommended Reading Matzinger, P.（危險的模式：有關自我的新概念），《科學》第296卷 (2002年)，301頁-305頁。 Matzinger, P. "The danger model: a renewed sense of self." Science 296 (2002): 301-5. |
| 12 | 改變還是死亡 Change or Die |
概述：病原體持續演化出新方法以避開免疫系統的偵查，這表示免疫系統也必須隨著改變。免疫系統一直與病原體共同演化著。舉例來說，T細胞的演化是為了對抗病原體，而部分病原如HIV演化出能在T細胞內生存的機制。病毒常藉由操控宿主防禦機制，如誘使被感染宿主細胞合成抗凋亡蛋白而能生存下來。免疫系統與病原體間的競賽將永無止境的持續下去。 Pathogens evolve constantly developing new ways of escaping immune surveillance, which means that the immune system must change as well. The evolution of the immune system is always co-evolution with pathogens. For example, T cells evolved to fight pathogens; then pathogens such as HIV capable of surviving in T cells evolved. Viruses often survive by manipulating the host defense machinery, for example, inducing the synthesis of anti-apoptotic proteins in the host cells they infect. The race between immune system and pathogens never ends. |
Dean, M., and M. Carrington, 等 〈CKR5構造基因中的對偶基因缺失限制HIV-1的感染與發展為AIDS〉，《科學》第273卷 (1996年)，1856頁-1862頁。 Dean, M., and M. Carrington, et al. "Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene." Science 273 (1996): 1856-62. Tram, U., and W. Sullivan. （延緩細胞核模裂解及有絲分裂於Wolbachia屬菌誘使的細胞質不相稱中所扮演之角色），《科學》第296卷 (2002年)，1124頁-1126頁。 Tram, U., and W. Sullivan. "Role of delayed nuclear envelope breakdown and mitosis in Wolbachia-induced cytoplasmic incompatibility." Science 296, no. 5570 (2002): 1124-6. |
| 13 | 學生口頭報告 Student Oral Presentations 課程評鑑 Course Evaluations |
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