人類的免疫系統被設計為保護宿主機能之完整性，亦即維持健康之狀態恆定。當此一恆定機制受到破壞，如傷燙傷、外來之侵襲物，免疫機制即被活化，以保護宿主。「先天性免疫系統」主要由「天然屏障」所組成，包括皮膚、黏膜、酵素，以及血球細胞中的嗜中性白血球（顆粒化的白血球），以保護宿主對抗許多種侵襲物。假如先天免疫系統無法保護宿主，則由「適應性免疫系統」取代。白血球是我們體內用來防禦外來病菌入侵的細胞。在白血球家族中，嗜中性白血球佔了血液中白血球含量的70％，它在人體的免疫系統中扮演著重要角色。嗜中性白血球通常只能存活數小時，因此，必須大量產生，才能肩負起防禦人體的任務。然而，過量的嗜中性白血球，又會導致免疫系統過度活化，產生種種過敏疾病。嗜中性白血球的促發指的是:先使其暴露於促發因子，如:腫瘤壞死因子(TNF-alpha)、血小板活化因子(PAF)而後會讓其處於對活化因子刺激時有更為強大之反應的一個狀態。亦即促發後的嗜中性白血球相較於未促發的會對活化因子的刺激有著更大的反應(促發反應)。這個反應常是由嗜中性白血球所引起的組織傷害的一個重要因素。然而目前這反應的訊息傳遞之分子機制並不甚清楚。由於類鐸蛋白受體(TLRs)的發現也使得我們對於先天性免疫的辨識機制有了更近一步的了解；先天性免疫系統透過了類鐸蛋白受體辨識入侵物的組成份並引起發炎反應。嚴重的燒燙傷會引起休克及可能破壞腸胃道黏膜的完整性而造成細菌轉位(bacterial translocation ,BT)到腸繫膜淋巴結(MLN)、肝臟、脾臟等處。高張食鹽水曾被主張用來作為thermal injury resuscitation，因為高張食鹽水可以給較小的體積，所以其可以減少水腫的發生。另外雖然高張食鹽水也曾被報導可以增加宿主對抗細菌的反應，但其分子機制目前並不甚清楚。在這研究裡得到一些結果: 嗜中性白血球的促發反應為TNF-alpha 和p38依賴性、類鐸蛋白受體(TLRs)辨識入侵物的組成份在先天性免疫系統中扮演著重要角色以及高張食鹽水藉由增加免疫細胞的類鐸蛋白受體(TLRs)的表現來增加宿主對抗細菌的反應。

Burns often leads to infection, due to damage to the skin's protective barrier. Burn injury has been repeatedly shown to induce considerable inflammatory and immune dysfunction. The innate immune system is a universal and ancient form of host defense against infection. Activation of innate immunity constitutes the first line of host defense against infection. Neutrophils are white blood cells and part of the immune system. They are the most common PMN (polymorphonuclear neutrophils) and accounted for 70% of all leukocytes. Neutrophils provided the first line of defense of the innate immune system by phagocytosing, killing, and digesting bacteria and fungi. Priming means a process whereby the response of neutrophils to an activating stimulus is potentiated, sometimes greatly, by prior to exposure to priming agents such as tumor necrosis factor-alpha(TNF-alpha), platelet-activating factor (PAF). Neutrophil priming causes a dramatic increase in the response of these cells to an activating agent; this process has been shown to be critical for neutrophil-mediated tissue injury both in vitro and in vivo. However, the intracellular signaling pathways used by neutrophil in response to pro-inflammatory stimuli have not been elucidated. The discovery of TLRs has made us understanding of the mechanisms of innate immune recognition. The innate immune system detectes the invasion of microorganism through TLRs, which recognize microbial components and trigger inflammatory responses. Severe burn injury produces shock and induces acute gastrointestinal derangement that may disrupt gastrointestinal mucosa integrity and facilitate the bacterial translocation (BT) to Mesenteric lymph node (MLN), liver, and spleen. Hypertonic saline (HTS) has been advocated in thermal injury resuscitation because of the possibility of giving less total volume of resuscitation fluid, with a resulting decrease in edema and the need for escharotomy. In this study, I found that priming effect of BM neutrophils is TNF-alpha and p38 dependent and TLRs play a critical role to the innate immunity by recognizing bacteria and HTS enhance host response to bacterial challenge by increasing TLRs of inflammatory cells.

目錄
中文摘要................................................I
英文摘要..............................................III
縮寫表………………………………………………………………..V
PART I Hypertonic Saline Enhances Host Defense to Bacterial Challenge by Augmenting Toll-like Receptors
摘要.....................................................1
前言.....................................................3
材料與方法...............................................8
結果....................................................16
討論....................................................22
圖表....................................................28
參考文獻................................................37
PART II Thermal Injury-induced Priming Effect of Neutrophil is TNF-alpha and p38 -Dependent
摘要....................................................40
簡介....................................................41
材料與方法..............................................46
結果....................................................52
討論....................................................60
圖表....................................................64
參考文獻................................................75

Part1
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