【正文】 參考教材 ? 醫(yī)學(xué)免疫學(xué) 何維主編 ? 現(xiàn)代動(dòng)物免疫學(xué) 王世若、王興龍、韓文瑜主編 。 ? 臨床免疫學(xué)研究和應(yīng)用 ? 圍繞著重大疾病如感染性疾病、腫瘤、自身免疫性疾病與過(guò)敏性疾病以及器官移植排斥等的發(fā)生發(fā)展機(jī)制、診斷與病程的動(dòng)態(tài)觀察和預(yù)后分析、治療與預(yù)防措施開(kāi)展應(yīng)用性研究。 ⑨ 免疫細(xì)胞的遷移觸發(fā)、遷移過(guò)程與定居機(jī)制。 ⑦ 免疫效應(yīng)分子的結(jié)構(gòu)、功能與作用機(jī)制。 ⑤ 獲得性免疫應(yīng)答的細(xì)胞與分子機(jī)制。 ③ 免疫細(xì)胞感受外界危險(xiǎn)信號(hào)、識(shí)別抗原的物質(zhì)結(jié)構(gòu)基礎(chǔ)。 3. 表面氨基酸殘基人源化 抗體人源化的主要技術(shù) 提高抗體 效應(yīng)功能 偶聯(lián)細(xì)胞毒物質(zhì) 雙特異性抗體 抗體 Fc突變 改變抗體糖基化 細(xì)胞內(nèi)抗體 抗體融合蛋白 提高抗體效應(yīng)功能 Mj macrophage IL8 Activated T cell D NH2 COOH IL2 Cytockines are lowmolecularweight regulatory proteins or glycoproteins secreted by white blood cells and various cells (vascular endothelial cell, epidermic cell and fibroblast ) in body in response to a number of stimuli. Cytokine Biological effects IL1 TNFa GMCSF MCSF FGF PDGF VEGF IL12 IL15 IL6 LIF OSM Chemokines TGFb IL10 IL11 IL13 sTNFR IL1ra PROINFLAMMATORY ANTIINFLAMMATORY Cytokine imbalance during inflammation 細(xì)胞因子的研究熱點(diǎn) 新細(xì)胞因子的基因克隆化 細(xì)胞因子受體的基因克隆化 細(xì)胞因子信號(hào)轉(zhuǎn)導(dǎo)機(jī)制 新一代細(xì)胞因子：高活性，多功能，低毒副作用，長(zhǎng)半衰期，高穩(wěn)定性 細(xì)胞因子作為生物應(yīng)答調(diào)節(jié)劑（ BRM）的臨床應(yīng)用 細(xì)胞因子表達(dá)調(diào)控 細(xì)胞因子基因治療 Infections occur when the physical barriers of epithelium are breached, or when pathogens adhere to the epithelium 1. Pathogen replication 2. Recruitment of neutrophils and macrophages 3. Inflammation Pathogen adherence to epithelium Pathogens are carried to the closest lymph node where they stimulate specific T and Bcells ? Production of specific antibodies = Adaptive immunity Innate immunity Adaptive immunity Activation of adaptive immunity by innate immunity Time course of primary infection in healthy individuals, and people who lack immune or adaptive immunity In the absence of innate immunity, there is also no adaptive immunity Infection is cleared from the body by bined actions of innate and adaptive immunity T Cells maitain the homostasis of innate inflammation Pathogen Danger signal Lymphocyte Inflammatory/Innate immune cell INNATE IMMUNITY ADAPTIVE IMMUNITY PROTECTION IMMUNOPATHOLOGY Failure of the immune system 1. Ineffective response Immunodeficiency 2. Overactive response Hypersensitivity 3. Autoreactive response Autoimmunity 免疫的基本功能 功能 正常表現(xiàn)（有利） 異常表現(xiàn)（有害） 免疫防御 immune defence 抗病原微生物 的侵襲 超敏反應(yīng) 易受感染或免疫缺陷病 免疫穩(wěn)定 immune homeostasis 清除損傷、衰老、死亡細(xì)胞 自身免疫性疾病 免疫監(jiān)視 immune surveillance 清除突變或畸變的惡性細(xì)胞 惡性腫瘤 ，病毒持續(xù)性感染 免疫學(xué)研究的主要內(nèi)容 ? 基礎(chǔ)免疫學(xué)研究 ①免疫系統(tǒng)的形成機(jī)制、免疫器官與免疫細(xì)胞組成以及不同種類(lèi)免疫細(xì)胞和亞群的形成過(guò)程與相互之間調(diào)控機(jī)制。 抗體人源化改造及人源抗體制備 1. 人 鼠嵌合抗體 ： 應(yīng)用基因工程技術(shù)將小鼠單克隆抗體的恒定區(qū)用人源抗體恒定區(qū)代替而拼接成嵌合抗體。 基因工程抗體： 利用基因工程技術(shù)來(lái)制備的抗體分子稱為基因工程抗體，是分子水平的抗體。 高度均一（結(jié)構(gòu)、特異性）。 由一個(gè) B細(xì)胞克隆產(chǎn)生。 用天然的抗原物質(zhì)免疫動(dòng)物，刺激多個(gè) B細(xì)胞克隆所獲得的免疫血清（含多種特異性抗體）。 Effector T cells In contrast to terminally differentiated B cells (plasma cells), there are several types of terminally differentiated effector T cells. CD8 T cells Cytotoxic T cells (recognize MHC class I molecules) CD4 T cells TH1 helper cells (activate macrophages) TH2 helper cells (induce differentiation of B cells into plasma cells and production of antibodies) Activation (cytokines) (recognize MHC II molecules) The immune system is maintained in a carefully regulated balance between the two polarised control arms, Th1 (cellular immunity) and Th2 (humoral immunity). In disease states the balance is skewed. multiple sclerosis, rheumatoid arthritis and type I diabetes, have a Th1 bias, whereas cancer patients have a Th2 bias. Th1 and Th2 Cells Do not Represent All CD4+ Cells More T helper subsets ? Th3: TGFβproducing CD4 T cells ? Tr1: IL10producing CD4 T cells ? Th9: IL9producing CD4 T cells ? Tfh: follicular helper T cells, located in the follicular regions of lymph nodes and spleen,follicular Th1