靶向DC-SIGN的抗原特異性免疫應(yīng)答研究
發(fā)布時間：2018-10-17 14:38
【摘要】： 盡管疫苗的出現(xiàn)已經(jīng)有效的改善了人類的健康進(jìn)程,但對疫苗的設(shè)計仍有諸多改善的必要,尤其在各種新的感染性疾病層出不窮,癌癥死亡率仍步步攀升的今天。因此,采取新的策略來改善疫苗的免疫原性,設(shè)計更為有效的治療性疫苗是當(dāng)前刻不容緩的問題。 樹突狀細(xì)胞(dendritic cells, DCs)是目前已知的功能最強(qiáng)大的職業(yè)抗原呈遞細(xì)胞(profesional antigen presenting cells, pAPCs),能以受體介導(dǎo)的內(nèi)吞、巨吞飲和吞噬等方式高效的攝取外界抗原并以多種機(jī)制來呈遞抗原;作為一個自然的免疫佐劑,在遭遇危險信號時能高表達(dá)CD80、CD83、CD86等共刺激分子,與MHC抗原肽復(fù)合物共同作用可有效的活化效應(yīng)T細(xì)胞,并且是唯一能活化na?ve T細(xì)胞的抗原呈遞細(xì)胞;在靜息狀態(tài)(steady state)的DCs細(xì)胞仍然可以有效的“抽樣調(diào)查(sample)”外界抗原,并組成性的呈遞(constitutive presentation)這些無害的外來抗原和自身抗原(30-80%為自身合成缺陷的蛋白),通過誘導(dǎo)調(diào)節(jié)性T細(xì)胞分化來誘導(dǎo)和維持外周耐受; DCs細(xì)胞兼具兩種看似矛盾的功能,正是通過它對“自身”和“非自身”抗原的判斷來決定免疫系統(tǒng)的不同反應(yīng),在適當(dāng)?shù)臅r候產(chǎn)生適當(dāng)?shù)膽?yīng)答或是耐受,從而維持機(jī)體免疫穩(wěn)態(tài);因此,利用DCs細(xì)胞來調(diào)控和改善治療性疫苗的免疫效應(yīng),上調(diào)或是下調(diào)特定的免疫反應(yīng),一貫是治療性疫苗設(shè)計的重要方向。 DCs細(xì)胞雖然具有強(qiáng)大的攝取抗原的功能,但它對抗原非特異的攝取和呈遞的方式會造成疫苗不能被有效呈遞,從而影響疫苗的后續(xù)效應(yīng)。將抗原靶向DCs,利用DCs來改善疫苗的免疫原性是重要的疫苗設(shè)計策略。隨著分子免疫學(xué)和DC細(xì)胞生物學(xué)的進(jìn)展,許多在DC特異表達(dá)的分子被鑒定,尋找適當(dāng)?shù)陌邢蛲緩匠蔀橐粋�歷久彌新的重要課題。 新近發(fā)現(xiàn)的一些DC限制性表達(dá)的凝集素受體成為目前關(guān)注的靶向新途徑,例如DEC205和DC-SIGN。DC-SIGN(DC-specific intracellular adhesion molecule-grabbing nonintegrin)受體是2002年發(fā)現(xiàn)的限制性表達(dá)于DC和某些組織巨噬細(xì)胞上的凝集素樣受體, DC-SIGN已經(jīng)被證實不僅是病原體受體,而且是重要的抗原受體,可有效的攝取處于粘膜組織的微量的HIV和CMV病毒顆粒,繼之可以MHC-I類分子和MHC-II
[Abstract]:Although the emergence of vaccines has effectively improved the human health process, but the vaccine design is still necessary for many improvements, especially in the emergence of various new infectious diseases, cancer mortality is still rising step by step today. Therefore, it is urgent to adopt new strategies to improve the immunogenicity of vaccines and to design more effective therapeutic vaccines. Dendritic cell (dendritic cells, DCs) is one of the most powerful occupational antigen-presenting cells known at present. (profesional antigen presenting cells, pAPCs), can efficiently ingest external antigens by receptor-mediated endocytosis, giant swallowing and phagocytosis and present antigens through various mechanisms. As a natural immune adjuvant, CD80,CD83,CD86 and other costimulatory molecules can be highly expressed in the presence of danger signals. The interaction with MHC antigen peptide complexes can effectively activate the effector T cells and is the only antigen-presenting cell that can activate na?ve T cells. DCs cells in resting (steady state) can still be effectively "sampled to investigate (sample)" external antigens. In addition, compositional presentation of (constitutive presentation), a harmless foreign antigen and autoantigen (30-80% is a self-synthetic defective protein), induces and maintains peripheral tolerance by inducing regulatory T cell differentiation. DCs cells have two seemingly contradictory functions. It is through its judgment of the "self" and "non-self" antigens that it determines the different responses of the immune system and, at the appropriate time, produces an appropriate response or tolerance, thereby maintaining the immune homeostasis of the body; therefore, DCs cells are used to regulate and improve the immune response of therapeutic vaccines, upregulating or down-regulating specific immune responses. It has always been an important direction in the design of therapeutic vaccines. Although DCs cells have a strong ability to ingest antigens, However, the nonspecific way of uptake and presentation of antigens will result in the vaccine being unable to be effectively presented, thus affecting the subsequent effects of the vaccine. Using DCs to improve the immunogenicity of DCs, is an important vaccine design strategy. With the development of molecular immunology and DC cell biology, many molecules specifically expressed in DC have been identified. Recently discovered lectin receptors, which are restricted by DC, have become a new target pathway. DEC205 and DC-SIGN.DC-SIGN (DC-specific intracellular adhesion molecule-grabbing nonintegrin) receptors, for example, are lectin-like receptors found in 2002 that are restricted to DC and certain tissue macrophages. DC-SIGN has been shown to be not only a pathogen receptor, but also an important antigen receptor. Effective uptake of microamounts of HIV and CMV virus particles in mucosal tissue, followed by MHC-I molecules and MHC-II
【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2005
【分類號】：R392
本文編號：2276998
[Abstract]:Although the emergence of vaccines has effectively improved the human health process, but the vaccine design is still necessary for many improvements, especially in the emergence of various new infectious diseases, cancer mortality is still rising step by step today. Therefore, it is urgent to adopt new strategies to improve the immunogenicity of vaccines and to design more effective therapeutic vaccines. Dendritic cell (dendritic cells, DCs) is one of the most powerful occupational antigen-presenting cells known at present. (profesional antigen presenting cells, pAPCs), can efficiently ingest external antigens by receptor-mediated endocytosis, giant swallowing and phagocytosis and present antigens through various mechanisms. As a natural immune adjuvant, CD80,CD83,CD86 and other costimulatory molecules can be highly expressed in the presence of danger signals. The interaction with MHC antigen peptide complexes can effectively activate the effector T cells and is the only antigen-presenting cell that can activate na?ve T cells. DCs cells in resting (steady state) can still be effectively "sampled to investigate (sample)" external antigens. In addition, compositional presentation of (constitutive presentation), a harmless foreign antigen and autoantigen (30-80% is a self-synthetic defective protein), induces and maintains peripheral tolerance by inducing regulatory T cell differentiation. DCs cells have two seemingly contradictory functions. It is through its judgment of the "self" and "non-self" antigens that it determines the different responses of the immune system and, at the appropriate time, produces an appropriate response or tolerance, thereby maintaining the immune homeostasis of the body; therefore, DCs cells are used to regulate and improve the immune response of therapeutic vaccines, upregulating or down-regulating specific immune responses. It has always been an important direction in the design of therapeutic vaccines. Although DCs cells have a strong ability to ingest antigens, However, the nonspecific way of uptake and presentation of antigens will result in the vaccine being unable to be effectively presented, thus affecting the subsequent effects of the vaccine. Using DCs to improve the immunogenicity of DCs, is an important vaccine design strategy. With the development of molecular immunology and DC cell biology, many molecules specifically expressed in DC have been identified. Recently discovered lectin receptors, which are restricted by DC, have become a new target pathway. DEC205 and DC-SIGN.DC-SIGN (DC-specific intracellular adhesion molecule-grabbing nonintegrin) receptors, for example, are lectin-like receptors found in 2002 that are restricted to DC and certain tissue macrophages. DC-SIGN has been shown to be not only a pathogen receptor, but also an important antigen receptor. Effective uptake of microamounts of HIV and CMV virus particles in mucosal tissue, followed by MHC-I molecules and MHC-II
【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2005
【分類號】：R392
【參考文獻(xiàn)】
相關(guān)期刊論文 前1條
1 黎萬玲;王槐志;倪兵;姜曼;吳玉章;;磁轉(zhuǎn)聯(lián)合脂質(zhì)體實現(xiàn)高效細(xì)胞轉(zhuǎn)染[J];免疫學(xué)雜志;2005年06期
，本文編號：2276998
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