抗原与获得性免疫应答Englishversion.ppt

1、Antigens and adaptive immune responses,抗原与获得性免疫应答,specific immunity,Specific immunity is established on the basis of the non-specific immunity. It can be acquired after individual was stimulated with a antigen.,I Definition and general nature,1. Antigen (Ag):,5 - 1. Antigen ( Ag ),Substances that co

2、mbine specifically with a B or T cells antigen-binding receptor can then induce an immune response (positive or negative ) are called antigens. Positive response results in the production of antibody / effector T cells, and that the negative response causes the antigen-specific non-reactivity， that

3、is tolerance.,Antigen (Ag),Antigen binding causes cytotoxic T cells,Memory T cell,Activated cytotoxic T cell,Antigen binding triggers release of antibodies,Memory B cell,Activated B cell,Antibodies,2.The basic natures of antigen,（1）immunogenicity（免疫原性)（2）immunoreactivity (反应原性 ) or antigenicity (抗原性

4、),The antigen molecule generally pose two natures, that is,(1) immunogenicity,Immunogenicity is the ability to induce a humoral and / or cell mediated immune response, including induce production of antibody and effector lymphocytes.,Activated B cell,antibody,Activated CTL,（2） immunoreactivity or an

5、tigenicity 抗原性,Antigenicity is the ability to combine specifically with the final products of the above responses (i.e., antibody and /or cell-surface receptors).,3、Hapten and varrier,Hapten： some small molecules, called haptens, are antigenic but incapable ,by themselves, of inducing a spedific imm

6、une response. In other words, they lack immunogenicity,carrier： small organic molecules that are antigenic but not immunogenic. Chemical coupling of hapten to a large protein, called a carrier, yields an immunoginic hapten-carrier conjugate.Animals immunized with such a conjugate produce antibodies

7、specific for the hapten determinant. The substance that can make the hapten be immunogenic ( is capable of inducing immune response) are called carrier.,HAPTEN-CARRIER CONJUGATES,A. Definition - Hapten-carrier conjugates are immunogenic molecules to which haptens have been covalently attached. The i

8、mmunogenic molecule is called the carrier.,B. Structure - Structurally these conjugates are characterized by having native antigenic determinants of the carrier as well as new determinants created by the hapten (haptenic determinants) as illustrated in the Figure 3.,Hapten ：,Haptens have the propert

9、y of antigenicity but not immunogenicity.,A substance that is non-immunogenic but which can react with the products of a specific immune response.,small molecules,immune response,+,carrier,hapten+carrier=complete antigen,II. FACTORS INFLUENCING IMMUNOGENICITY,1、chemical and physical nature of antige

10、ns（1）chemical characteristic（2） molecule size（3）complicated chemical structure（4）conformation and accessibility2、Host （1）foreignness（2）genetic characteristics of the host（3）Age, sex, and state of health3、immunized Route,1、chemical and physical nature of antigens,（1）chemical nature glycoprotein, lipo

11、protein、polysaccharide、LPS DNA，chromosome、histone in the activated lymphocyte,Aoto-antibody for self-DNA, histone,Antinuclear antibody (ANA),Autoimmuno diseases,（2）molecule size,10kD,100kD,100kD ）,直链氨基酸,加苯环氨基酸（2%酪氨酸）,（免疫原性很弱）,（免疫原性大大增强）,（4）分子构象(conformation)的易接近性(accessibility),抗原性 +,酪氨酸 多聚丙氨酸 谷氨酸 多

12、聚赖氨酸,+,（2）genetic characteristics of the host Genetic control of immune responsiveness, largely confined to genes within the MHC. MHC gene products, which function to present processed antigen to T cells, play a central role in determining the degree of immune responsiveness.,（3） Age, sex, and state

13、 of health,III Specificity of antigen,1. Specificity of antigen ：The characteristic that antigen only binds the antibody and sensitized lymphocyte specifically, is called specificity of antigen（ Specificity ）,The effect of composition and spatial structure of chemical group on the hapten-antibody sp

14、ecificity,Anti-serum,position,response,composition,NH2,SO3H,anti,NH2,NH2,-R,NH2,R,-R,Ortho-,Meta-,Para-,R = SO3H,R = ASSO3H2,R = COOH,+,+,+,serum,2、抗原决定基 （antigenic determinant）：抗原分子中决定抗原特异性的特殊的化学基团，它是TCR/BCR及抗体特异性结合的基本单位，又称表位( epitope )。,Antigenic determinants or epitopes are the immunologically ac

15、tive regions of an immunogen that bind to antigen-specific membrane receptors on lymphocytes (TCR/BCR) or to secreted antibodies.,Epitope or Antigenic Determinant,That portion of an antigen that combines with the products of a specific immune response.,antigen,antigen,antigen,5、 antigenic valence (抗

16、原的结合价),antigenic valence is the numbers of antigenic functional determinant which bind to antibody molecules. The hapten is univalence, and the natural antigen is generally macromolecule, consists of various and multiple antigenic determinants, so it is called polyvalent antigen, and can bind multip

17、le antibodies.,多价抗原,没有发现一个表位同时被T细胞和B细胞识别。,*on surface of molecule,antigen,antibodyCDR3,epitope,B cell epitope,The side on the antigen molecule that is recognized by BCR and antibody is called B cell epitope.,*The epitope is the smallest unit on the antigen that can binds to antibody.,* conformationa

18、l determinants,（1）B cell epitope,（2）T cell epitope,The peptide that is presented by MHC molecule and recognized by TCR is called T cell epitope .,TCR,MHC,HIV peptide,TCR recognize MHC/antigenic peptide,TCR,Antigenic peptide,MHC-II,T cell,APC,Ep1,Ep2,Ep3,T Cell epitope,Antigenic peptides recognized b

19、y T cell form trimolecular complexes with a TCR and an MHC molecule,irrelevant to conformation of a protein molecule,Mainly depend on the amino acid sequence of the peptide,relevant to the expression of MHC molecule of the host,irrelevant to a site where the peptide is in the protein molecule,Compar

20、ison of epitope of T and B cell,T cell epitope B cell epitope,Receptor TCR BCR,MHC molecule required to display none required processed antigen,character liner peptides natural polypeptide, LPS, polysaccharide, organic compound,515 amino acids, 57 monosaccharideor 57 nucleotide,Epitope type liner co

21、nformational, liner,side any on the surface,size,8 12 amino acids (CD8+) ,12 17 amino acids (CD4+),B cell epitope（ hapten ）,natural antigens (polyvalent antigen multi-determinants),T cell epitope,8、 common antigen and cross-reaction,There are multiply antigenic determinants on the surface of the nat

22、ural antigens. Each B cell determinant induces production of a specific antibody. Thereby a complicated antigen can induce production of multiply antibodies. A same or similar antigenic determinant that exists between the two different antigens is called common antigen .,The reaction that antibody r

23、eacts with same or similar antigenic determinant between the different antigens is called cross-reaction.,IV type of antigen,1. Depend on whether need the Th for producing the antibody,* thymus dependent antigen, TD-Ag （胸腺依赖抗原）,*thymus independent antigen, TI-Ag （ 胸腺非依赖抗原）,TD and TI are complete ant

24、igen (完全抗原),TI and TD antigen,1,2,CD40/CD40L,B cell,B cell,Th cell,TI- antigen,TD antigen,CD4,（4） hetorophilic antigen （异嗜性抗原）, or Forssam antigen,Hemolytic streptococcus B C antigen乙型溶血性链球菌细胞壁C抗原 M antigen M抗原,Streptococcus infection链球菌感染,Acute Glomerulonephritis,LPS of E.coli O14,Colonic mucosa结肠粘

25、膜,Ulcer colitis溃疡性结肠炎,Glycoprotein of Cardiac valve心瓣膜的糖蛋白 heart muscle,Rheumatic fever风湿热,Streptococcus A A族链球菌,Glomerular basement membrane肾小球基底膜,The hetorophilic antigens are common antigen, which are irrelevant to species and exist in human, animal, plant and microorganism.,急性肾小球肾炎,When the immu

26、ne system encounters a conventional T-dependent antigen, only a small fraction (1 in 104 -105) of the T cell population is able to recognize the antigen and become activated (monoclonal/oligoclonal response). However, there are some antigens which polyclonally activate a large fraction of the T cell

27、s (up to 25%). These antigens are called superantigens.,2、超抗原 ( SUPERANTIGENS ),超抗原,TCRV b,抗原肽,MHC-II a,T 细胞,APC,超抗原（superantigens, SAg）,能同时与MHC分子及TCR多肽结合，从而激活多克隆T细胞的蛋白质大分子。,超抗原能与MHC-II分子及TCRb链结合，从而造成T细胞的非特异性活化。,V Adjuvant (免疫佐剂),Substances that can mix with antigen and enhance the immune response t

28、o the immunogen are called adjuvants.,complete Freunds adjuvant includes mineral oil, woolfat (羊毛脂) and inactivatedMycobacterium tuberclosis （结核杆菌）,incomplete Freunds adjuvant includes mineral oil and woolfat,1、Most effective : Freunds adjuvant（弗氏佐剂）,2、mineral salt (矿物盐)：aluminium potassium sulfate (硫酸铝钾盐)、sodium salt, Ammonia salt,3、5-CG- 3 : six base sequence ( CpG),Antigen（抗原）Antigenicity （抗原性）Immunogen（免疫原） Immunogenicity（免疫原性）Toleragen（耐受原）Allergen（变应原）,