2Objectives: * Define antigen and hapten. * Define immunogenicity & antigenicity.* Define epitope.* Describe the chemical nature and different classes of Ag.* Discuss various determinants of antigenicity.* Describe the major classes of MHC molecule.* Explain the role of MHC in immune mechanism (antigen processing, antigen presentation & immune response).Anantha NarayananCh 15
3Immunogen: A substance that induces a specific immune response. Antigen (Ag): A substance that reacts with the products of a specific immune response.Hapten: A substance that is non-immunogenic but which can react with the products of a specific immune response. Haptens are small molecules which could never induce an immune response when administered by themselves but which can when coupled to a carrier molecule.Epitope or Antigenic Determinant: That portion of an antigen that combines with the products of a specific immune response. Any given antigen may have several epitopes. Each epitope is recognized by a different antibody.Antibody (Ab): A specific protein which is produced in response to an immunogen and which reacts with an antigen.
4Epitopes: Antigen Regions that Interact with Antibodies
7C- Method of administration: 1. Dose.2. Route.3. Adjuvants.Substances which are added to or emulsified with an Ag so as to enhance the Ab production.They can be Inorganic salts : Aluminium hydrooxide- Bacterial products: Bordetella pertussis (with Diphtheria, Tetanus toxoids)
8The chemical nature of immunogens: 1. Proteins.2. Polysaccrides.3. Nucleic acids.4. Lipids.
9Types of Antigens: T-dependent Ag: Do not directly stimulate the production of antibody without the help of T cells.- Proteins.- Immunogenic over a wide dose range and do not cause tolerance.- Produce immunological memory- Requires processing by APCs.
10 T-independent Ag:Can directly stimulate the B cells to produce antibody without the requirement for T cell help.Polysaccharides.- Immune response is dose dependent.Too little – non immunogenicToo much – toleranceDo not produce immunological memory.- Do not require processing by APCs.
12Antigen processing and presentation Exogenous Ag Endogenous Ag
13Superantigens Not processed. Interact with the MHC class II molecule outside of the peptide - binding groove.Bind only to the Vβ segment of TCR.
14Antigenic specificity: Species Specificity.Isospecificity. (Human blood group)Autospecificity.Heterogenetic (heterophile) Specificity.
15Major histocompatibility complex (MHC) The MHC is a large complex region of highly polymorphic genes located on the short arm of chromosome 6.Also known as human leukocyte antigens or HLA.There are 3 classes of MHC molecules: MHC Class I, Class IIand Class III.. They differ among members of the same species.. Each person has two haplotypes.
16MHC class I & II play role in antigen presentation T cell receptor only recognize antigens combined with major histocompatability (MHC) proteins on the surface of cells.MHC Class I: Found on all cells.MHC Class II: Found on phagocytes.MHC class I & II play role in antigen presentationFor T cell activation, T cell receptor (TCR) must recognize the processed antigens (in peptide fragment forms) which bound to MHC class I or II molecules(MHC restriction).
18Table 1. Polymorphism of class I MHC genes LocusNumber of alleles (allotypes)HLA-A218HLA-B439HLA-C96HLA-E, HLA-F and HLA-GRelatively few alleles
19Table 2. Polymorphism of class II MHC genes Locus Number of alleles (allotypes)HLA-DPA HLA-DPB12 88HLA-DQA HLA-DQB17 42HLA-DRA HLA-DRB1 HLA-DRB3 HLA-DRB4 HLA-DRB5HLA-DM and HLA-DORelatively few alleles