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chapter 2. Antigen. 抗原. Conceptions Immunogenicity and Specificity of Antigen Classification of Antigen Superantigen and Adjuvant. Ⅰ . Conception.
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chapter 2 Antigen 抗原 Conceptions Immunogenicity and Specificity of Antigen Classification of Antigen Superantigenand Adjuvant
Ⅰ.Conception Antigen (抗原) Complete antigen (完全抗原) Hapten (半抗原) Tolerogen (耐受原) Allergen (变应原)
1.Antigen (Ag) pathogen→B cell →corresponding antibody (Ab) combine specifically Ag A.Definition of Ag B ---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 ︱ BCR —TCR B.2 important properties of Ag T immunogenicity antigenicity
B.2 important properties of Ag Immunogenicity antigen ↓ IS ↓induce IR ↓ products of IR (Ab/effector T cells) Combine specifically ---the ability for inducing an IR, including induce production of antibody and effector T cell 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 →immunogenicity →antigenicity ---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
2.Complete antigen & hapten A.Complete antigen (完全抗原) ---Substances that have both immuno-genicity and immunoreactivity(antigenicity) B.Hapten(半抗原) ---Substances that have immunoreactivity, butlack of immunogenicity
(二硝基苯) 半抗原 combine with (有免疫反应性) combine with combine with anti-dinitrobezene (抗二硝基苯) (无免疫原性) (有免疫原性) •Hapten couple(偶联) to protein or other carriers (载体) to form complete antigen •hapten+carrier = complete antigen
3.Tolerogen & allergen Tolerogen antigen→ →T/B → → response negative (state of specific nonresponse) “immune tolerance” (免疫耐受) Allergen antigen → →T/B → → high response “hypersensitivity/allergy” (超敏反应/变态反应)
1.Decisive factors for immunogenicity Ⅱ.Immunogenicity and Specificity of antigen A.Foreigness(异物性) • various microbes • allogenic substance • heterogenic protein (such as immune sera) Non-self substances Self tissue (including: changed or cryptical) 在胚胎期未与免疫活性细胞充分接触过的物质均为异物 B.Physicochemical characteristics
B.Physicochemical characteristics Chemical propertyMolecule weight Glutin (明胶) Glutin +2% tyrosine→→ (酪氨酸) Y Y MW>100kD 免疫原性弱 免疫原性增强 Complexity of structureMolecular conformation and accessibility (分子构象和易接近性)
Tyrosine Glutan poly-alanine poly-lysine Immunogenicity +++ ± +++ 分子构象和易接近性不同,其免疫原性也不同 Physical property
C.Host D.Immunized route Genetic characteristics of the host Age, sex, and state of health
2. Specificity of antigen 多价抗原 多价抗原 induce AD binding to AD specificity of immunogenicity specificity of immunoreactivity A.Antigenic determinant (AD) 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 Antigenic valence 能与抗体结合的抗原决定基(表位)的数目,称为抗原的结合价
A. Antigenic determinant (AD) AD Definition Ag 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 Ag B antigen Ag antigen T
The chemical composition and spatial structure of AD decide specificity of Ag (半抗原) 抗间位氨基苯磺酸抗体 苯磺酸基 苯砷酸基 甲酸基
Antigenic valence AD ---The numbers of epitope which can bind to antibody 多价 抗原 能与抗体结合的抗原决定基(表位)的数目,称为抗原的结合价 *Natural antigen is polyvalent antigen
B.Classification of AD According to structure of AD • linear determinant •conformational determinant According to location of AD on Ag molecule • functional determinant • cryptical determinant According to AD recognized byT 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 *linear determinant *location in the insideof antigen 1,2: B细胞表位 3 :T 细胞表位 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 2 •B cell epitope---epitope recognized by BCR/Ab 3 1 *conformational determinant or linear determinant *location on the surfaceof natural antigen 3 B细胞可识别线性表位或构象决定基,且无需加工处理
C.Common antigen and cross-reaction Common antigen 两种不同抗原具有相同或相似的抗原决定簇,则称为共同抗原(common antigen) Cross-reaction 抗体对具有相同或相似的抗原决定簇的不同抗原的反应,称为交叉反应(共同抗原又称交叉反应抗原) 交叉反应 Ag1 Ag2
1.Depend on whether need the Th cell for producing the antibody Ⅲ. Classification of antigen A.Thymus dependent antigen(TD-Ag) B.Thymus independent antigen(TI-Ag)
2. Depend on the consanguinity between the Ag and organism (亲缘关系) • Xenogenic 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) or Forssam antigen • E.Idiotype Ag
Ⅳ.Superantigen and adjuvant 1. Superantigen A.Conception B. Types 一种在极低浓度下(1~10ng/ml)即可激活大量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 exogenous superantigen 如金葡菌肠毒素A~E endogenous superantigen 如逆转录病毒的蛋白产物 TCR+T cell superantigen 如热休克蛋白(HSP) B cell superantigen 如金葡菌蛋白A(SPA) C.Characteristic and mechanism
a terminal of SAg directly binding to nonpolymorphic region of MHC-Ⅱ the other terminal of SAg combine with TCRV of CD4+T cell *The difference between common Ag and Sag (Conbinate site, not processed by APC, no restriction-MHC)
2.Adjuvant A.Conception 某些物质预先或与抗原同时注入体内,可增强机体对该抗原的免疫应答或改变免疫应答类型,此类 物质称为佐剂 B.Types 卡介苗、脂多糖、弗氏佐剂…… C.Mechanisms D.Use