医学免疫学英文教学课件：chapter 4 Antigen (Ag）

1、1Chapter 4 Antigen (Ag）Part IntroductionPart Factors Affecting Immunogenicity Part Specificity and Cross-Reaction of Antigens Part Classification of Antigens Part Important Antigens in Medicine Part Superantigen and Adjuvants ContentsPart Introduction. DefinitionAntigen (Ag): An antigen is a substan

2、ce that can stimulate immune system to produce a specific immune response, and can react specifically with the immune response products in vitro or in vivo.The products of immune response: antibodies and/or effector lymphocytes. B cells Antibody Ag T cells Effector T cellsStimulate immune system to

3、produce a specific immune response.React specifically with the immune response products in vitro or in vivo.Key points：. Properties of antigen 1. Immunogenicity：An ability to stimulate the body to evoke a specific immune response.Immunogens: substances with immunogenicity2. Immunoreactivity:Antigeni

4、cityAn ability to combine with corresponding Ab or sensitized T lymphocytes. AgTBT1. Immunogenicity: to induce the specific immune response. AgTBTEffector T cell2. Immunoreactivity: to combine with corresponding Ab or sensitized T lymphocyte. Complete antigen and hapten1. Complete antigen: Both Immu

5、nogenicity and Immunoreactivity. 2. Hapten: Only Immunoreactivity. Hapten+carrier complete antigen Carrier: enhance the immunogenicity of hapten. Tolerogen and allergenTolerogen: substances to induce specific tolerance.Allergen: substances to induce hypersensitivity (type I)TypesPhenotypeImmunogenic

6、ityImmunoreactivityOther name Agpositivenormal+Immunogenhypersensitivity+AllergennegativeImmune tolerance-TolergenPart Factors affecting immunogenicity . Factors related to antigens . Factors related to host. Methods of immunization . Factors related to antigens ForeignnessAccording to Burnet, forei

7、gnness means substances which never contact with embryonic lymphocytes. . Factors related to antigens 1. Foreignness: “Non-self”substances and self componentsXeno-substances: various pathogens and their products, xeno-protein, etc.Allo-substances: ABO blood type, HLA, etc.Self components: - release

8、of sequester antigen - degeneration2. Physical and chemical properties(1) Molecular weight:reasonable large molecule( 10.0 kd)more stationarymore surface structure for lymphocyte to recognize (2) Chemical composition and structure Proteins Polysaccharides Nucleic Acids Lipids aromatic ring ring line

9、ar(3) Physical nature Polymer monomerParticulate Soluble . Factors related to host1. Genetic background (Species, Individual)2. Age, sex and healthy status . Pathway of immunization 1. Dosage of antigen: the optimal immunogen dose for immunization2. Times of injection: multiple immunization 3. Ways:

10、Intracutaneoussubcutaneousmuscleintravenous/intraperitoneal cavityoral (saliva)4. Adjuvant:Certain substances which can enhance or change the type of immune response.What measures can be taken to increase the titers of antibody when preparing antibodies against sheep red blood cells in mice? Why? Pa

11、rt . Specificity and cross reaction of antigen SpecificityExist in both immunogenecity and immunoreactivityThe basis of immunologic diagnosis and immunologic therapy. Antigenic determinant 1. Antigenic determinants (epitope) are small particular chemical groups existing in antigen which combine with

12、 TCR/BCR or Ab. Polypeptide antigen-5-23 amino acid residues Polysaccharide antigen-5-7 monosaccharides Nuclear acid antigen-6-8 nucleotide2. Antigenic valence: Total number of determinants which can be bound by antibody or antigenic receptor of lymphocytes. Most natural antigens are polyvalence ant

13、igen.Hapten is monovalence antigen. . Classification of antigenic determinants1. According to the site and structure of antigenic determinants Conformational determinants Sequential (or linear) determinants Conformational determinantsConformational determinants are formed by amino acid residues that

14、 arent in a sequence but become spatially juxtaposed in the folded protein.They are normally exist on the surface of antigen molecules.They are recognized by B cells or antibody. Sequential (or linear) determinantsEpitopes formed by several adjacent amino acid residues are called linear determinants

15、.They exist on the surface of antigen molecules or inside molecules.They are mainly recognized by T cells, but some also can be recognized by B cells. T/BB2. According to types of cells recognizing antigenic determinantsT cell determinants (T cell epitopes): TCRB cell determinants (B cell epitopes):

16、 BCR T cell epitopeAntigenic determinants recognized by T cells (TCR)Composition:PeptidesSequential determinants(Exist in anywhere of Ag)Processed by APCMHC presentationSize8-23 residuesB cell epitopeAntigenic determinants recognized by B cells（BCR）and AbComposition:Peptide, polysaccharides, nucleic

17、 acidsConformational determinants or sequential determinants (exist on the surface of Ag)Recognized directlyNo APC and MHCSize5-15 residuesComparison T cell epitope and B cell epitope T cell epitope B cell epitopeStructure linear epitope conformational epitope or linear epitope Receptor TCR BCRFeatu

18、res proteins proteins, polysaccharides Size 5-23 amino acid residues 5-15 amino acid residues or 5-7 monosaccharides or 5-8 nucleotidesLocation any part of antigen mostly exist on the surface of antigenMHC molecules yes no APC yes no Functional determinant: epitopes exist on the surface of Ag which

19、can be recognized by BCR or combined with Ab easily.Immunodominant epitopes: specially important determinant. Hidden determinant: epitopes exist inside of Ag which can not be recognized by BCR or combined with Ab easily. Common antigen and cross reactionCommom antigen: different Ags own the same epi

20、tope or their epitopes have similar structure, these epitopes are called common antigen.Heterophilic antigen: common antigen among human, animal or microbes.A B+ BA ACAnti-B serumAnti-A, C Ab + +Anti-A serumAnti-A, B AbCross reaction: reaction between the same Ab and different Ags with same or simil

21、ar determinants.Mechanism of cross reaction:-common Ag determinant.-similar structure of Ag determinant.Significance: -Because there are some common antigen determinants between different microbes, so the antiserum against one kind of Ag might also react with another Ag and cause a cross reaction. -

22、In clinic, existence of cross reaction may lead to wrong diagnosis.Part . Classification of Ag. According to immunogenicity of Ag. According to dependence of T cells. According to source of Ag. Others. According to immunogenicity of Ag -Complete Ag -Hapten . According to dependence of T cells1.TD-Ag

23、 (thymus dependent Ag): TD-Ag can stimulate B cells to produce Ab only with the help of T cells.Most TD-Ags are proteinMore kinds of determinants, each kind with less numbersInduce HI and CMIStimulate B cells to produce: IgG, IgM, IgAImmune memory2. TI-Ag (thymus independent Ag): stimulate B cells t

24、o produce Ab without the help of T cells.Most TI-Ags are polysaccharidesThe same repeated determinantsCan not induce CMIOnly induce B cells to produce IgMNo memory responseTD-AgTI-AgComponentsProtein,more kindsPolysaccharide,repeated epitopeHelp of T cellYesNoImmune reponseHI and CMIHIType of Abmore

25、，IgGIgMAffinity of AbHighLowImmune memoryYesNo Comparison of TD-Ag and TI-Ag. According to the sources of AgXenoantigenAlloantigenAutoantigenHeterophilic Ag . OtherslChemical componentsprotein polysacchride nucleic acid lipidlNatural Ag and artificial Ag Part . Important Ags in medicine . Pathogens

26、and their products 1. Pathogens: Surface antigen “Vi” Ag Somatic Ag “O” Ag Flagellar Ag “H” Ag 2. Exotoxin and toxoid Exotoxin: Produced by G+ bacteria, Strong immunogenicity and pathogenicity. Toxoid: Under suitable conditions, exotoxin loses its toxicity without affecting its immunogenicity, then

27、the exotoxin turned into toxoid.Anti-toxin . Immune serum: animal serum contains Abs after immunized by some AgsThe Janus face of immune serum:Neutralize the toxicity of exotoxinsSerum disease. Heterophilic Ag (forssman Ag)-Common Ags are shared by different species-No specificity of species -Signif

28、icance: immunopathology diagnosis . Alloantigen 1. Antigen of red blood cell (blood typing)ABO system -very important in transfusion Rh system (in Chinese 99%RH+) -heamolytic disease of the newborn2. Human leukocyte antigen, HLA system -relate to transplantation rejection -very important in immune r

29、egulation . Autoantigen 1. Release of sequestered Ag2. Modification of protein. Tumor antigen Tumor specific Ag (TSA) -Only express on the tumor cells but normal cellsTumor associated Ag (TAA) -Its expression is higher on tumor cells but low on normal cells, ex: AFP(-fetoprotein), CEA(carcinoembryon

30、ic antigen)Part . Superantigen and adjuvants. Superantigen (SAg): Antigens that can stimulate a plenty of T/B cells non-specifically and induce a very strong immune response with a extremely low concentration. SuperantigenConventional AntigenThe mechanism of SAg is different from that of Ag or mitogen.The mechanism of SAg is different from that of Ags or mitogen.T cell SAg: exotoxin, protein of reverse transcript virusB cell SAg: