Overview of the Immune System

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1 Overview of the Immune System Immune System Innate (Nonspecific) Adaptive (Specific) Cellular Components Humoral Components Cell-Mediated Humoral (Ab)

2 Antigens

3 Definitions Immunogen Antigen (Ag) Hapten Epitope or Antigenic Determinant Antibody (Ab)

4 Factors Influencing Immunogenicity Contribution of the Immunogen Foreignness Size Chemical Composition Primary Structure Secondary Structure Tertiary Structure Quarternary Structure Sequence determinants Conformational determinants

5 Factors Influencing Immunogenicity Contribution of the Immunogen Foreigness Size Chemical Composition Physical Form Particulate > Soluble Denatured > Native

6 Factors Influencing Immunogenicity Contribution of the Immunogen Foreigness Size Chemical Composition Physical Form Degradability Ag processing by Ag Presenting Cells (APC)

7 Factors Influencing Immunogenicity Contribution of the Biological System Genetics Species Individual Responders vs Non-responders Age

8 Factors Influencing Immunogenicity Method of Administration Dose Route Subcutaneous > Intravenous > Intragastric Adjuvant Substances that enhance an immune response to an Ag

9 Chemical Nature of Immunogens Proteins Polysaccharides Nucleic Acids Lipids Some glycolipids and phosopholipids can be immunogenic for T cells and illicit a cell mediated immune response

10 Polysaccharides Properties Polymeric structure Polyclonal B cell activation Yes -Type 1 (TI-1) Types of Antigens No - Type 2 (TI-2) T-independent Resistance to degradation Examples Pneumococcal polysaccharide, lipopolysaccharide Flagella

11 Proteins Structure Examples Microbial proteins Non-self or Altered-self proteins Types of Antigens T-dependent

12 Hapten-carrier conjugates Definition Structure native determinants haptenic determinants Haptenic determinants Native determinants

13 Antigenic Determinants Recognized by B cells and Ab Composition Proteins, polysaccharides, nucleic acids, haptens Sequence (linear) determinants Conformational determinants Size 4-8 residues

14 Antigenic Determinants Recognized by B cells and Ab Composition Size Number Limited (immunodominant epitopes) Located on the external surfaces of the Ag Fe

15 Composition Antigenic Determinants Recognized by T cells Proteins (some lipids) Sequence determinants Processed MHC presentation (lipid presentation by MHC-like CD1) Size 8-15 residues Number Limited to those that can bind to MHC

16 Superantigens Definition Conventional Antigen Superantigen Monoclonal/Oligoclonal T cell response 1:10 4-1:10 5 Polyclonal T cell response 1:4-1:10

17 Definition Superantigens Examples Staphylococcal enterotoxins Staphylococcal toxic shock toxin Staphylococcal exfoliating toxin Streptococcal pyrogenic exotoxins

18 Determinants Recognized by the Innate Immune System Adaptive Immune System Discrete Determinants Reacts with a specific pathogen Innate Immune System Broad Molecular Patterns Reacts with a variety of pathogens

19 Determinants Recognized by the Innate Immune System PAMPs Pathogen Associated Molecular Patterns PRRs Pattern Recognition Receptors

20 PAMP Microbial cell wall components Mannosecontaining carbohydrates PRR Complement Mannose-binding protein Biological Consequence of Interaction Opsonization; Complement activation Opsonization; Complement activation Polyanions Scavenger receptors Phagocytosis Lipoproteins of Gram + bacteria Yeast cell wall components TLR-2 (Toll-like receptor 2) Macrophage activation; Secretion of inflammatory cytokines

21 PAMP Double stranded RNA LPS (lipopolysaccharid e of Gram bacteria Flagellin (bacterial flagella) TLR-3 TLR-4 TLR-5 PRR Biological Consequence of Interaction Production of interferon (antiviral) Macrophage activation; Secretion of inflammatory cytokines Macrophage activation; Secretion of inflammatory cytokines

22 PAMP PRR Biological Consequence of Interaction U-rich single stranded viral RNA TLR-7 Production of interferon (antiviral) CpG containing DNA TLR-9 Macrophage activation; Secretion of inflammatory cytokines

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