IgG抗體【知識研究】

1、IgG抗體 ANTIBODY,1,資料類,免疫球蛋白的結(jié)構(gòu),（ Structure of Ab Molecules）,2,資料類,同種異型（allotype)： 同一種屬不同個體間免疫球蛋白分子所具有的不同的抗原特異性標(biāo)志。,由C區(qū)決定，主要反映在Ig分子的CH和CL上的一個或數(shù)個氨基酸的差異，又稱為遺傳標(biāo)志。,3,資料類,獨(dú)特型(idiotype, Id) ： 同一個體內(nèi)不同B細(xì)胞克隆產(chǎn)生的免疫球蛋白分子所特有的抗原特異性標(biāo)志。,由超變區(qū)決定,4,資料類,IgG分子的四種亞型,IgG1,IgG4,IgG3,IgG2,5,資料類,主要以單體形式存在，抗原結(jié)合價(jià)為2價(jià) 出生后3個月開始合成，35

2、歲接近成人 血清中含量最高，占血清總Ig的75-80% 產(chǎn)生比較晚，是再次應(yīng)答的主要抗體 半衰期最長(t 23天) 分布最廣，易通過毛細(xì)血管壁，是血管外的主要抗體 唯一能通過胎盤的Ig，新生兒抗感染免疫起重要作用 激活補(bǔ)體 IgG13（經(jīng)典），IgG4（替代） 結(jié)合細(xì)胞 吞噬細(xì)胞調(diào)理作用 NK細(xì)胞，吞噬細(xì)胞介導(dǎo)ADCC 結(jié)合SPA協(xié)同凝集實(shí)驗(yàn),特性：又稱為胎盤球蛋白,6,資料類,功能：,抗感染的主要抗體,新生兒抗感染免疫的重要抗體 介導(dǎo)II,III型超敏反應(yīng) 介導(dǎo)自身免疫,7,資料類,功能,IgG抗體是反映人體免疫功能的重要指標(biāo)。 根據(jù)結(jié)構(gòu)的不同IgG抗體可分為4 個亞類,即IgG1, IgG

3、2, IgG3 和IgG4。 這4個亞類的生物學(xué)特性不同,因此它們在疾病的發(fā)生發(fā)展過程中發(fā)揮不同的作用.,8,資料類,功能,針對細(xì)菌和病毒抗原產(chǎn)生的抗體中(例如破傷風(fēng)毒素或膜蛋白成分都是T細(xì)胞依賴型抗原) , IgG1占主導(dǎo)地位,有時(shí)伴隨IgG3的產(chǎn)生, IgG2水平較低。,9,資料類,功能,特異性皮炎( atop ic dermatitis)是一種慢性復(fù)發(fā)性皮膚炎癥疾病,特異性皮炎患者血清中針對花粉或塵螨的特異性IgE和IgG4水平升高。,10,資料類,功能,青霉素過敏患者血清中, IgG3 和IgG4 陽性的百分率分別為28. 05% , 13. 39%和12. 80% ,表明IgG3和I

4、gG4抗體在青霉素超敏反應(yīng)中發(fā)揮重要作用。,11,資料類,IgG抗體與HDN,各亞類激活補(bǔ)體經(jīng)典途徑的能力為IgG3 IgG1 IgG2 , 所以IgG3 在各亞類中溶血性最強(qiáng), 發(fā)生的HDN最嚴(yán)重。,12,資料類,IgG抗體與HDN,從患兒及患兒母親血清中IgG亞類含量的構(gòu)成來看, 雖均以IgG1 為主, 但患兒體內(nèi)IgG1 的比例較母親體內(nèi)高, 而其他3種亞類均略低于母體, 說明了IgG1 含量升高對新生兒溶血病有著更重要的作用。,13,資料類,IgG抗體與HDN,孕婦血清中IgG特異性抗體效價(jià)持續(xù)升高, 并且IgG1 亞類含量也顯著高者, 可預(yù)報(bào)新生兒溶血病的發(fā)生, 當(dāng)IgG3 也顯著升

5、高時(shí), 提示新生兒溶血嚴(yán)重。,14,資料類,The immune system consists of two functional components: Innate immune system Prevents penetration and spread of infectious agents by a variety of physical, biochemical and cellular barriers (skin, mucosa, lysozymes, complement, phagocytes) Adaptive immune system Develops a spe

6、cific immunological memory after the first attack. This leads to a stronger, faster and more effective response upon renewed contact with the same agent. Lymphocytes and immununoglobulins are the key elements Humoral immunity B-cells plasma cells immunoglobulins Cell mediated immunity T-cells Helper

7、 T-cells & Cytotxic T-cells,15,資料類,In humoral immunity B-cells recognize soluble or cell surface antigens (on extracellular microbes ) and differentiate into antibody secreting plasma cells. In cell-mediated immunity helper T-cells recognize antigens on the surfaces of antigen-presenting cells and s

8、ecrete cytokines, which stimulate B-cells and T-cells. Cytotoxic T-cells recognize antigens on infected cells and kill these cells.,16,資料類,17,資料類,18,資料類,19,資料類,20,資料類,relative serum concentrations IgG1 IgG2 IgG3 IgG4 differences in flexibility of the IgG3 IgG1 IgG4 IgG2 hinge region differences in b

9、iological properties Fab part + antigen effector functions via Fc part activation of complement IgG3 IgG1 IgG2 IgG4 induction of phagocytosis FcgRI CD 64: IgG3 IgG1 IgG4 (opsonisation)FcgRII CD 32: IgG3 IgG1 IgG2 binding to FcgR of effector cells FcgRIII CD 16: IgG3 = IgG1 CD 16: neutrophil granuloc

10、ytes, monocytes, macrophages , NK cells CD 32: monocytes, subpopulation of macrophages, granulocytes, eosinophils, B cells CD 64: monocytes, activated granulocytes,21,資料類,IgG1 Main response to virall and bactteriall prottein anttigen exposure Immune response tto capsulle pollysaccharide Acttivattiio

11、n compllementt Efffiicientt binding tto llymphocyttes via Fc recepttor Auto-antibodies IgG2 Predominantimmune response tto pollysacchariide antigens of bactteria such as pneumococci group A sttreptococci and Haemophillus iinfflluenzea IgG3 High-affiniittyantbodies tto protein antigens strongest comp

12、llementt acttiivattiion efficientt bindiing to lymphocytes viia Fc recepttor auto-antibodiies IgG4 Responses to chronic allergic stimullation Immune response tto alergens even after hyposensitization Blocking the IgE response,22,資料類,decrease of one IgG subclass + increase of other subclass total IgG

13、 level may normal. determination of IgG subclass levels is important, even when the total IgG level is within or only slightly below the reference range of healthy individuals. IgG subclass deficiency is not excluded by a normal or even high total IgG concentration! The finding of a decreased level

14、of one of the IgG subclasses can never provide a definite diagnosis, but should rather be considered as an indication of a disturbance of the immune system, requiring further diagnostic investigation.,23,資料類,Autoimmune / atopic diseases Bronchial asthma IgG2, IgG3 Diabetes variable Idiopathic thromb

15、ocytopenic purpuraIITP IgG2, IgG4 Systemic lupus erythematosus IgG3, IgG4 Immunodeficiencies Bone marrow transplantation IgG2, IgG4 CVID (common variable immunodeficiency) IgG1, IgG2, IgG4 High-dose corticosteroids IgG2, IgG3 HIV infection IgG2, IgG4 Chemotherapy, radiation exposure IgG2 Wiskott-Aldrich disease IgG4 Infections Otitis media (pneumo