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Antigens

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Antigens

  1. 1. Eugene P. Mayer Office: Bldg. #2, Rm. B19 Phone: 733-3281 Email: MAYER@MED.SC.EDU
  2. 2. Overview of the Immune System Immune System Innate (Nonspecific) Adaptive (Specific) Cellular Components Humoral Components Cell-Mediated Humoral (Ab)
  3. 3. Antigens
  4. 4. Definitions <ul><li>Immunogen </li></ul><ul><li>Antigen (Ag) </li></ul><ul><li>Hapten </li></ul><ul><li>Epitope or Antigenic Determinant </li></ul><ul><li>Antibody (Ab) </li></ul>
  5. 5. Factors Influencing Immunogenicity Contribution of the Immunogen <ul><li>Foreignness </li></ul><ul><li>Size </li></ul><ul><li>Chemical Composition </li></ul><ul><ul><li>Primary Structure </li></ul></ul><ul><ul><li>Secondary Structure </li></ul></ul><ul><ul><li>Tertiary Structure </li></ul></ul><ul><ul><li>Quarternary Structure </li></ul></ul>Conformational determinants Sequence determinants
  6. 6. Factors Influencing Immunogenicity Contribution of the Immunogen <ul><li>Foreigness </li></ul><ul><li>Size </li></ul><ul><li>Chemical Composition </li></ul><ul><li>Physical Form </li></ul><ul><ul><li>Particulate > Soluble </li></ul></ul><ul><ul><li>Denatured > Native </li></ul></ul>
  7. 7. Factors Influencing Immunogenicity Contribution of the Immunogen <ul><li>Foreigness </li></ul><ul><li>Size </li></ul><ul><li>Chemical Composition </li></ul><ul><li>Physical Form </li></ul><ul><li>Degradability </li></ul><ul><ul><li>Ag processing by Ag Presenting Cells (APC) </li></ul></ul>
  8. 8. Factors Influencing Immunogenicity Contribution of the Biological System <ul><li>Genetics </li></ul><ul><ul><li>Species </li></ul></ul><ul><ul><li>Individual </li></ul></ul><ul><ul><ul><li>Responders vs Non-responders </li></ul></ul></ul><ul><li>Age </li></ul>
  9. 9. Factors Influencing Immunogenicity Method of Administration <ul><li>Dose </li></ul><ul><li>Route </li></ul><ul><ul><li>Subcutaneous > Intravenous > Intragastric </li></ul></ul><ul><li>Adjuvant </li></ul><ul><ul><li>Substances that enhance an immune response to an Ag </li></ul></ul>
  10. 10. Chemical Nature of Immunogens <ul><li>Proteins </li></ul><ul><li>Polysaccharides </li></ul><ul><li>Nucleic Acids </li></ul><ul><li>Lipids </li></ul><ul><ul><li>Some glycolipids and phosopholipids can be immunogenic for T cells and illicit a cell mediated immune response </li></ul></ul>
  11. 11. Types of Antigens T-independent <ul><li>Polysaccharides </li></ul><ul><li>Properties </li></ul><ul><ul><li>Polymeric structure </li></ul></ul><ul><ul><li>Polyclonal B cell activation </li></ul></ul><ul><ul><ul><li>Yes -Type 1 (TI-1) </li></ul></ul></ul><ul><ul><ul><li>No - Type 2 (TI-2) </li></ul></ul></ul><ul><ul><li>Resistance to degradation </li></ul></ul><ul><li>Examples </li></ul><ul><ul><li>Pneumococcal polysaccharide, lipopolysaccharide </li></ul></ul><ul><ul><li>Flagella </li></ul></ul>
  12. 12. Types of Antigens T-dependent <ul><li>Proteins </li></ul><ul><li>Structure </li></ul><ul><li>Examples </li></ul><ul><ul><li>Microbial proteins </li></ul></ul><ul><ul><li>Non-self or Altered-self proteins </li></ul></ul>
  13. 13. Hapten-carrier conjugates <ul><li>Definition </li></ul><ul><li>Structure </li></ul><ul><ul><li>native determinants </li></ul></ul><ul><ul><li>haptenic determinants </li></ul></ul>Native determinants Haptenic determinants
  14. 14. Antigenic Determinants Recognized by B cells and Ab <ul><li>Composition </li></ul><ul><ul><li>Proteins, polysaccharides, nucleic acids </li></ul></ul><ul><ul><li>Sequence (linear) determinants </li></ul></ul><ul><ul><li>Conformational determinants </li></ul></ul><ul><li>Size </li></ul><ul><ul><li>4-8 residues </li></ul></ul>
  15. 15. Antigenic Determinants Recognized by B cells and Ab <ul><li>Composition </li></ul><ul><li>Size </li></ul><ul><li>Number </li></ul><ul><ul><li>Limited (immunodominant epitopes) </li></ul></ul><ul><ul><li>Located on the external surfaces of the Ag </li></ul></ul>Fe
  16. 16. Antigenic Determinants Recognized by T cells <ul><li>Composition </li></ul><ul><ul><li>Proteins (some lipids) </li></ul></ul><ul><ul><li>Sequence determinants </li></ul></ul><ul><ul><ul><li>Processed </li></ul></ul></ul><ul><ul><ul><li>MHC presentation (lipid presentation by MHC-like CD1) </li></ul></ul></ul><ul><li>Size </li></ul><ul><ul><li>8 -15 residues </li></ul></ul><ul><li>Number </li></ul><ul><ul><li>Limited to those that can bind to MHC </li></ul></ul>
  17. 17. Superantigens Monoclonal/Oligoclonal T cell response 1:10 4 - 1:10 5 <ul><li>Definition </li></ul>Conventional Antigen Superantigen Polyclonal T cell response 1:4 - 1:10
  18. 18. Superantigens <ul><li>Definition </li></ul><ul><li>Examples </li></ul><ul><ul><li>Staphylococcal enterotoxins </li></ul></ul><ul><ul><li>Staphylococcal toxic shock toxin </li></ul></ul><ul><ul><li>Staphylococcal exfoliating toxin </li></ul></ul><ul><ul><li>Streptococcal pyrogenic exotoxins </li></ul></ul>
  19. 19. Determinants Recognized by the Innate Immune System <ul><li>Adaptive Immune System – Discrete Determinants </li></ul><ul><ul><li>Reacts with a specific pathogen </li></ul></ul><ul><li>Innate Immune System – Broad Molecular Patterns </li></ul><ul><ul><li>Reacts with a variety of pathogens </li></ul></ul>
  20. 20. Determinants Recognized by the Innate Immune System <ul><li>PAMPs – Pathogen Associated Molecular Patterns </li></ul><ul><li>PRRs – Pattern Recognition Receptors </li></ul>
  21. 21. Macrophage activation; Secretion of inflammatory cytokines TLR-2 (Toll-like receptor 2) Lipoproteins of Gram + bacteria Yeast cell wall components Phagocytosis Scavenger receptors Polyanions Opsonization; Complement activation Mannose-binding protein Mannose-containing carbohydrates Opsonization; Complement activation Complement Microbial cell wall components Biological Consequence of Interaction PRR PAMP
  22. 22. Production of interferon (antiviral) TLR-3 Double stranded RNA Macrophage activation; Secretion of inflammatory cytokines TLR-5 Flagellin (bacterial flagella) Macrophage activation; Secretion of inflammatory cytokines TLR-4 LPS (lipopolysaccharide of Gram – bacteria Biological Consequence of Interaction PRR PAMP
  23. 23. Macrophage activation; Secretion of inflammatory cytokines TLR-9 CpG containing DNA Production of interferon (antiviral) TLR-7 U-rich single stranded viral RNA Biological Consequence of Interaction PRR PAMP

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