设为首页 | 加入收藏夹

八文网 - 汇聚八方文档 - 做最优秀的免费文档下载网站

你需要学习的课题

文档类型：

Microsoft PowerPoint PPT 演示文稿文档大小：5.86M

and of interacting surfaces of Ab and AgAbAg
你需要学习的课题:
1.「好」的免疫原(immunogen) 有些什0特质
2. 什0叫做抗原决定区 epitope 有何特性
4. 抗体分子的基本构造及各部位的名称.
5. 抗体的种类,特性及功能.
6. 单株抗体与多株抗体. Outline
versus antigenicity
2.Epitopes
3.Basic structure of antibodies (Abs)
4.Ab-binding site
5.Ab-mediated effector functions
6.Ab classes and biological activities
7.Antigenic determinants on (Ig)
8.The B-cell receptor
9.The Ig superfamily
10. Monoclonal Abs Immunogenicity vs. Antigenicity
Immunogenicity 免疫性:the ability to induce an Ab immune response
Antigenicity 抗原性:the ability to combine specifically withAb andor cell-surface receptors (IgTCR)- that response is usually called an antigen,it is more appropriately called an immunogen.
- Although all molecules that have the propertyof immunogenicity also have the property the reverse is not true.
Some small molecules, called haptens, areantigenic but incapable, by themselves, immune response. In otherwords, they lack
DNP: dinitrophenol{(bovine serum albumin)
Landsteiners work demonstrated both the specificity of the immune system for small structural variations on haptens and the enormous diversity of epitopes that the immune system is capable of recognizing.
Factors That Influence properties of an immunogen:- Foreignness- Molecular size- Chemical composition and heterogeneity- Susceptibility to antigen processing and biological system:- Genotype of the recipient animal- Immunogen dosage and route of the greater the between two species, the greater thestructural (and therefore the between them.Some macromolecules (e.g, collagen andcytochrome c) were highly evolution and therefore displayvery little immunogenicity across diversespecies some (e.g,corneal tissue and sperm) are from the immune system, sothat if these tissues are injected even intothe animal from which they will function as immunogens.
Molecular size- There isacorrelation between the and its
- The best immunogens tend to have amolecular mass >daltons (Da).- Generally, substances less thanDa arepoor compositionand complexity- Synthetic homopolymers tend to regardless of their size.
All4levels of protein organization 0primary, secondary, tertiary and quaternary 0contribute to the structural complexity of aprotein and hence affect its
Four levels of structureFor Ab (B cell) responses:
Proteins are the most potent immunogens, with ranking second. Lipids and nucleic acids of an infectious agent generally do not serve as immunogens unless they are complexed with proteins or
ForTcell responses:
Only proteins and some lipids (glycolipids and phospholipids) serve as immunogens.
Susceptibility to and development of both Ab-mediated immune responses ofTcells with Ag that has beenprocessed and presented together with insoluble macromolecules generallyare more immunogenic than small, solubleones because the larger molecules are morereadily phagocytosed and processed.
Molecules that cannot be degraded (e.g,polymers of D-amino acids) andor cannotbe presented with MHC molecules areThe biological system contributesto of the recipient dosage and route
Doses: too low no response, too high tolerance
Exposure: repeated administration (booster) overaperiodof time is usually more effective
Routes: orally (从口入的)parenterally (非从口入的)
- intravenous (iv) : intoavein
- intradermal (id) : into the skin- subcutaneous (sc) : beneath the skin- intramuscular (im) : intoamuscle- (ip) : into the peritoneal cavity为什0 Ag 的量,接触次数及路径与免疫反应的强度有关Adjuvants 佐剂Latin adjuvare, to helpSubstances that, when mixed with anantigen and injected with it, enhancethe immunogenicity of that antigen.
Effects of adjuvants
1. antigen persistence is prolonged - slower release of antigen at the injection sitee.g, alum 明矾[AlK(SO4)2,
2. costimulatory signals (p. 159) are enhanced - increased expression of B7 molecules on APCmaximal activation of TH cells
3. local inflammation is increased
4. nonspecific proliferation of lymphocytes is stimulated - formation ofadense, mass of 肉芽肿e.g, incomplete Freunds adjuvant (IFA),complete Freunds adjuvant (CFA)
1. 在实验动物中制备抗体时,经常使用CFA (complete Freunds adjuvant),其作用机转为何
2. 为何局部发炎反应能增强Ab 反应 do not interact with, or immunogen molecules; instead, theyrecognize discrete sites on the epitopes, or antigenic determinants.
epitopes: active regions of animmunogen, that bind to receptors on lymphocytesor to secreted Abs.T-cell and B-cell epitopes- The recognition of antigens byTcells andBcellsis fundamentally different.- BecauseBcells bind antigen that is free insolution, the epitopes they recognize tend to behighly accessible sites on the exposed surfaceof the immunogen.- T-cell epitopes are peptides combined with MHCmolecules. Thus, there is no requirement forsolution accessibility such as B-cell epitope.
Properties of B-cell epitopesB-cell epitopes on native proteins generallyare composed of hydrophilic a.a. on theprotein surface that are to membrane-bound or free Ab.
2. B-cell epitopes may be composed of sequential or nonsequential amino acids.
Sperm whale myoglobulin B-cell epitopesHen egg-white lysozyme (HEL) composesone nonsequential epitopeContact with Ab light chainContact with Ab heavy andlight chainsContact with Ab heavy chainAb to native HEL does not bind to reduced HELB-cell epitopes tend to be located in flexible regionsof an immunogen and display site mobility.
- site mobility of epitopes maximizes the Abs binding siteComplex proteins contain multiple epitopes, some of which are
- Most of the surface ofaglobular protein is Some epitopes, called immune response inaparticular animal thanother epitopes.Basic structure of of immune serumImmune seraafter reactionwith Agg- globulin (gG)
Immunoglobulin (Ig):IgG, IgM, IgA, IgE, IgDAntibody (Ab)Ab molecules chains-Adimer of heterodimers
V: variable
C: constant
g :IgG
a :IgA→numerous small peptides
Fab binding
Fc to the Fab fragment could react with both whereas antibody to the Fc fragment reacted only with theHchain.
Fab consists of portions of anHandaL chain.
Fc contains onlyHchain components.
spectrum of antibodiesin the serum g-globulin fraction
- Multiple of Ab-producing plasma cells
- Myeloma protein: 95% of the serum Ig- Bence-Jones proteins: the excess light chainsin the urine.
- MOPC: mineral-oil induced plasmacytomain miceHeavy and light chainsare folded into between domains of an Ab molecule
2 Ag-binding Domains- each contains about 110 a.a. residues and anintrachain disulfide bond that formsaloop of 60 a.a.
Domains- hypervariable regions:= regions (CDR)- framework regions (FR)
- diversity in the VH domain is concentrated in of a.a. residues in the VH and VL domainsCDRs bind Agsnumber of different amino acids atagiven of the most common amino acid atagiven changes may be inducedby antigen binding: after binding to the Ag: before binding to the effector functions- Antibodies generally do not kill or solely by binding to them.
WhileVregions bind to Ag, the CH regionis responsible foravariety of with other proteins, cells, andtissues that result in the effector functionsof the Ab Effector (调理作用) is promoted by AbAbs activate complement (补体) (chapter cell-mediated cytotoxicity- Some Abs can cross epithelial layers by transcytosisAb promotes opsonization through abinding to Fc receptors (FcR)on phagocytesAb activates cytolysis or promotes opsonization toCreceptors on cell-mediated cytotoxicity (ADCC)
movement of Ab across epithelial layer- delivery of IgA to the mucosal surfaces of and urogenital tracts,as well as its export to breast milk- transplacental transport of IgG from mother to fetusSecretory IgA in Breast MilkBind to microbes in babys digestive tract andthereby prevent their attachment to the walls ofthe gut and their subsequent passage into thebodys tissues.Ab classes andbiological activities
5 major classes of secreted antibody IgGmost abundant in serum80% of total serum Ig4IgG subclasses
4 subclasses of human IgG size of the hinge regionno. position of the interchain -S-S- bondvaried effectiveness in placenta transfer Pentamer- monomer on the in secretion- 1st Ab in neonates- 1st Ab in more efficient chain isrequired for the monomers to formpentameric IgM- also present in Dimermonomers, dimers, trimers andtetramers in serum- predominant in external breast milk, saliva, tears, andmucus of the bronchial, digestive IgADimers and tetramers in secretion withasecretory of Secretory IgAIgEpotent biological low conc. in serum- mediates the immediate for the symptomsof hay fever, asthma, hives, shockAllergen cross-linkage of receptor-bound IgE on mast cells- induces degranulation, causingrelease of substances that together with IgM, is themajor membrane-bound Igon to function in theactivation ofBcellsno biological has been determinants on Igs
3 Antigenic Determinants of determinants that collectively defineeach H-chain class and subclass, and each L-chaintype and subtype Determinants- differences in amino acids inCregions, whichoccur in some, but not all, members unique amino acid sequence of theVregions ofagiven Ab. In some cases, an idiotype is the siteB-cell ReceptorFc receptors bound to Fc regions of Absneonatal Fc receptorFc receptors - essential for many of thebiological functions of Absmovement of Abs across cell membranes, e.g,the transfer of IgG from mother to fetus acrossthe acquisition of Ab by many cell cells, eosinophils, macrophages, and naturalkiller cells (a linker between Ab molecules andvarious types of cells)The Ig superfamilyThe Ig superfamily -1The Ig superfamily -2Monoclonal AbsClonal Selection of monoclonal antibodies to predict isagood immunogenWhat are the differences between B-cell epitopes and T-cell diagram ofatypical IgG molecule and label each of the chains, bonds, regions, sites, fragments and domains.
How does Ab kill or remove pathogensWhat is the principal of making monoclonal antibody

ppt文档的标签：需要课题学习

更多推荐标签：地毯总代理评审记录服务推广冶金新技术高等物理化学辛亥革命论文洗涤活动方案改制方案就业促进行为种类构建和谐社会张翼飞化工储运企业客户资源邓小平开放企业金融会计广播工作流程网络资讯项目协议书现代语言学环境监测论文正修篮球场设备所保养网上数据流图面料报价格式文件控制医生进修计划八路抢答器案例八答案广告认知