博士生课程3(1)-抗原课件

1、抗 原 (Antigen，Ag) Conceptions Immunogenicity and Specificity of Antigen Classification of Antigen Superantigen and Adjuvant1.Antigen (Ag) BCRTCRA.Definition of Ag -抗原是能与B 、 T 淋巴细胞抗原识别受体结合,启动免疫应答,并能与应答产物 ( 抗体或效应T细胞) 发生特异性结合的物质B.2 important properties of Ag immunogenicity antigenicityBTcombine specific

2、allypathogenB cell corresponding antibody Ag(Ab) B.2 important properties of Ag Immunogenicity antigen IS induce IR products of IR (Ab/effector T cells)Combine specificallyimmunogenicity 免疫原性是指能够刺激机体产生特异性免疫应答，包括诱导产生抗体及效应性T 淋巴细胞的能力 Antigenicity/immunoreactivity -the ability for inducing an IR, includ

3、ing induce production of antibody and effector T cell -the ability to combine specifically with the Ab or effector T cell induced by its own -能与其诱生的抗体或效应性T细胞发生特异性结合的能力,称为抗原性或免疫 反应性antigenicity2.Complete antigen & haptenA.Complete antigen (完全抗原)-Substances that have both immuno-genicity and immunorea

4、ctivity(antigenicity) B.Hapten (半抗原)-Substances that have immunoreactivity , but lack of immunogenicity hapten+carrier = complete antigen半抗原(无免疫原性) Hapten couple(偶联) to protein or other carriers (载体) to form complete antigen(有免疫原性)(二硝基苯) combine with(有免疫反应性)combine withcombine withanti-dinitrobezene

5、 (抗二硝基苯).Immunogenicity and Specificity of antigen1.Decisive factors for immunogenicityA.Foreigness(异物性) Non-self substances Self tissueB.Physicochemical characteristics在胚胎期未与免疫活性细胞充分接触过的物质均为异物 various microbes allogenic substance heterogenic protein (such as immune sera) (including: changed or cryp

6、tical) Glutin(明胶)Glutin +2% tyrosine (酪氨酸) 免疫原性弱 免疫原性增强B.Physicochemical characteristicsMW10kDMolecule weightComplexity of structure Molecular conformation and accessibility（分子构象和易接近性） YYC.Host D.Immunized route Genetic characteristics of the host Age, sex, and state of healthA.Antigenic determinant

7、 (AD)2. Specificity of antigen 抗原分子中决定抗原特异性的特殊化学基团称为抗原决定基,又称为表位(epitope); 是与TCR/ BCR及抗体特异性结合的基本单位抗间位氨基苯磺酸抗体(半抗原)The chemical composition and spatial structure of AD decide specificity of Ag 苯磺酸基苯砷酸基甲酸基B. Classification of AD According to structure of AD functional determinant cryptical determinant A

8、ccording to location of AD on Ag molecule linear determinant conformational determinant According to AD recognized by T or B cell T cell epitope B cell epitope Hapten epitope and carrier epitope(i.e. B cell epitope and T cell epitope) T cell epitope-epitope recognized by TCR B cell epitope-epitope r

9、ecognized by BCR/Ab T细胞只识别经加工处理的线性表位，一般不识别构象决定基*linear determinant*location in the inside of antigen*conformational determinant or linear determinant*location on the surface of natural antigen B细胞可识别线性表位或构象决定基，且无需加工处理 321,2: B细胞表位3 :T 细胞表位31 溶血性链球菌 肾小球基底膜 大肠杆菌O14型 肠 粘 膜共同抗原 急性肾小球肾炎共同抗原 溃疡性结肠炎. Class

10、ification of antigen1.Depend on whether need the Th cell for producing the antibodyA.Thymus dependent antigen(TD-Ag)B.Thymus independent antigen(TI-Ag)2. Depend on the consanguinity between the Ag and organismXenogenic Ag （异种抗原）B. Allogenic Ag（同种异型抗原）C.Autoantigen（自身抗原）D.Heterophilic antigen (异嗜性抗原)

11、 or Forssam antigen E.Idiotype Ag (亲缘关系)独特型抗原（idiotypic antigen) T细胞抗原识别受体（TCR）及BCR或Ig的V区所具有的独特的氨基酸顺序和空间构象，可诱导自体产生相应的特异性抗体，这些独特的氨基酸序列称为独特型(idiotype, Id)抗原而成为自身免疫原，所诱生的抗体（即抗抗体，或称Ab1）称抗独特型抗体（AId)。因此能以Ab1-Ab2-Ab3-Ab4的形式进行下去，从而形成免疫网络，调节免疫应答 .Superantigen and adjuvant 1. Superantigen 一种在极低浓度下(110ng/ml)即可

12、激活大量T细胞克隆,并产生极强的免疫应答的特殊抗原类物质,称为超抗原A.ConceptionB. Typesexogenous superantigen 如金葡菌肠毒素AEendogenous superantigen 如逆转录病毒的蛋白产物C. Characteristic and mechanism TCR+T cell superantigen 如热休克蛋白(HSP)B cell superantigen 如金葡菌蛋白A(SPA) T cell superantigen1. 具有强激活T细胞（CD4+T细胞）作用，只需极低浓度即可激活5%-20%淋巴细胞克隆，产生极强的免疫应答的抗原。2

13、. 抗原无需处理，直接与MHC-II类分子和TCR-V结合。3. 无MHC限制性，同MHC-II类分子结合，增加TCR与SAg的亲和力。4. 可激活T细胞，又可致T细胞产生免疫耐受或抑制。普通抗原与超抗原不同识别机制的比较 Classification of adjuvant organic adjuvants: BCG inorganic adjuvants: Al(OH)3 synthesized adjuvants: polyI:CCytokines Can be used with vaccines alone or in conjunction with liposomes. Cytokines used are IL-1, 2, 6, 7, 12 and IFN-. Used to stimulate proliferation of T-cells, antibody production, MHC expression. IFN- has