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Download ANTIGEN Molecule that is recognized by specific antibody or T cells
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Fe A. Bartolome, MD, FPASMAP Department of Microbiology Our Lady of Fatima University IMMUNOGENS • Protein or carbohydrate that challenges the immune system and that can initiate an immune response • Molecules that induce an immune response • Any substance that is capable of inducing an immune response (humoral or cellular or both) ANTIGEN • Molecule that is recognized by specific antibody or T cells • Molecules that react with antibodies • Substance that is recognized by a particular immunoglobulin or T receptor and serve as target of an immune response ANTIGEN PROPERTIES: 1. Foreignness 2. Chemical composition 3. Molecular size 4. Chemical complexity 5. Genetic constitution of host animal 6. Method of administration HAPTEN • Molecule that is not immunogenic by itself but can react with specific antibody • A low MW substance which by itself cannot stimulate an immune response • Has to be bound to a carrier molecule • Cannot activate helper T cells unable to bind to MHC proteins since are not polypeptides • Univalent cannot activate B cells by themselves EPITOPE • Antigenic determinant • Actual molecular structure that interacts with a single antibody molecule or T cell receptor • Types: 1. Linear epitope – formed by a specific sequence 2. Conformational epitope – formed by a 3D structure EPITOPE B CELL EPITOPE • Region that is recognized by immunoglobulins • Size can encompass 3-20 amino acids or sugar residues EPITOPE T CELL EPITOPE • Region recognized by T cell receptor • recognized by T lymphocytes only after being processed and presented in association with an MHC protein ADJUVANT • Substance, which when mixed with an antigen, enhances the magnitude and duration of the immune response • Functions: 1. Prolong retention of immunogen 2. Increase the effective size of the immunogen 3. Stimulate local influx of macrophages or immune cells to the injection site ADJUVANT EXAMPLES: 1. Complete Freund’s adjuvant • Heat-killed mycobacteria in mineral oil 2. Liposomes – defined lipid complexes 3. Bacterial cell wall components 4. Polymeric surfactants 5. Cholera toxin & E. coli lymphotoxin – potent adjuvants for IgA MHC genes • Human leukocyte antigens • Chromosome 6 • Determines success of tissue and organ transplants • Bind peptide antigens and present them to T cells • Expression: co-dominant • Polymorphic diverse many alleles at each locus from each parent • Polygenic MHC glycoproteins CLASS I MHC MOLECULES • Coded for by HLA-A, HLA-B, HLA-C • Heterodimer polymorphic (heavy) chain noncovalently bound to a 2-microglobulin (chr. 15) • Heavy chain composed of: 1. Hypervariable region – important for recognition of self and non-self 2. Constant region – CD8 T cell binding site • Found on all nucleated cells and platelets • Present endogenous peptides CLASS II MHC MOLECULES • Coded for by HLA-D (DP,DQ,DR) • Heterodimer noncovalently associated chain and chain • Composed of: 1. Hypervariable region – responsible for polymorphism 2. Constant region – CD4 T cell binding site 3. Invariant chain (Ii) – protect the binding site • Found on APC’s • Present exogenous antigens MHC glycoproteins CLASS III MHC MOLECULES • Between class I and class II; soluble proteins • Contain immunologically important genes encoding for: 1. Cytokines – TNF and lymphotoxin 2. Complement components – C2 and C4 • Does not have genes that code for histocompatibility antigens BIOLOGIC IMPORTANCE: 1. Antigen recognition by T cells CD8 T cells class I MHC molecules CD4 T cells class II MHC molecules 2. Autoimmune diseases occur in people who carry MHC genes (e.g. HLA-B27 in ankylosing spondylitis) 3. Success of organ transplants is determined by compatibility of MHC genes of donor and recipient. Important Features of Some Human MHC Gene Products Class I Genetic loci (partial HLA-A, -B, and –C list) Class II HLA-DP, -DQ, and –DR Polypeptide composition MW 45,000 + 2M (MW 12,000) chain, chain, and Ii chain Cell distribution All nucleated somatic cells Antigen-presenting cells, activated T cells Present peptide antigens to CD8 T cells CD4 T cells Size of peptide bound 8 – 11 residues 10 – 30 or more residues Comparison of Class I and Class II MHC Proteins Class I MHC Class II MHC Present antigen to CD4+ T cells No Yes Present antigen to CD8+ T cells Yes No Found on surface of all nucleated cells Yes No Found on surface of professional APCs Yes Yes Encoded by genes in the HLA locus Yes Yes Expression of genes is codominant Yes Yes Multiple alleles at each gene locus Yes Yes Composed of 2 peptides encoded in HLA locus No Yes Composed of one peptide encoded in the HLA locus & a 2-microglobulin Yes No Feature
