Antigens, Antigenicity, Immunogenicity

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Antigens, Antigenicity, Immunogenicity

• Reading Chapter 3

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Major Concepts

• Antigen
• Substance that can be recognized by
  immunoglobulin receptors of B cells and T cell
  receptors when complexed with a major
  histocompatibility molecule (MHC)
• Immunogenicity vs Antigenicity
• Definitions and examples
• General ranking of immunogen potency
• Immunogens in cell-mediated immunity
• Factors influencing immunogenicity of an antigen
• Foreigness
• Molecular Size
• Chemical composition and complexity
• Ability to be processed and presented with MHC

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• Foreigness
• Immunogens must be recognized as non-self
• Size of the phylogenetic difference and the
  immune response are directly related
• BSA from cow or chicken
• Exceptions collagen, sperm, corneal tissue

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• Molecular Size
• Activity of immunogens and their MW
• Immunogenicity and ability to be phagocytosed,
  processed and presented by antigen presenting
  cells

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Chemical Composition and Heterogeneity
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Cell-mediated immunity lipids and glycolipids as
immunogens
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Biological Systems and Immunogenicity

• Immunogenicity of an antigen is influenced by
  three main factors of a biological system
• Genotype of recipient
• Ex. McDeritt and inbred mice strains
• Dose and route of antigen administration
• Ex. Pneumococcal capsular polysaccharide and
  optimum concentration dose
• Boosters
• Administration of adjuvants
• Intravenous, intradermal, subcutaneous,
  intraperitoneal, intramuscular

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• Adjuvants
• Substances when mixed with antigen and injected
  into organism enhance immunogenicity of the
  antigen

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• Epitopes or antigenic determinants
• Immunologically active regions of an immunogen
  that binds membrane receptors on lymphocytes or
  secreted antibodies

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• Receptors of adaptive immunity antibodies and
  TCRs
• B cell antibody receptors
• Recognize soluble antigenic epitopes with
  accessible sites on exposed surface of the
  immunogen
• T cell receptors (TCRs)
• Recognize antigenic epitopes presented by MHC on
  the surface of an antigen presenting cell (APC)
  or an altered self-cell

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• B cells and their epitopes
• Characteristics of binding of epitope to Fab
  fragment of antibody
• Recognition is dependent upon
• Size of the epitope
• Shape of the epitope
• Small and large antigens bind differently
• Ex. Angiotensin II

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• Binding of large antigenic epitopes
• Ex. Hen egg-white lysozyme (HEL) and
  neuraminidase
• Antibody and epitope contact along a large flat
  undulating surface
• Hydrophilic amino acids in epitope provide an
  accessible surface for antibody binding

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Antigen-binding regions of Fab fragments
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• Site of antibody- antigen interaction can be
  sequential or non-sequential
• Sequential
• Primary sequence
• Ex. Sperm whale myoglobin
• Non-sequential
• Tertiary sequence
• Ex. Egg white lysozyme

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• Experiments showing the importance of tertiary
  structure of epitope in non-sequential
  antigen-antibody binding

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• Flexibility of B cell epitopes
• Multiple overlapping B cell epitopes
• Immunodominant epitopes

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• Gell and Banacerraf (1959) compared humoral and
  cell mediated responses to native and denatured
  proteins antigens following secondary
  immunization
• Why?
• 1980, T cells and recognition of processed
  antigenic epitopes presented by APCs or altered
  self-cells

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• T cells and antigen recognition
• Formation of the TCR-peptide-MHC trimolecular
  complex

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• T cells and recognition of internal epitopes
• Experiments looking at amino acid protrusion,
  comparison with B cell recognition

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• Using haptens to study antigenicity
• K. Landsteiner
• Generation of immunogenic hapten-carrier
  conjugates
• Chemical structure and immune specificity
• Clinical uses
• Drug allergies

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• Receptors of Innate Immunity
• Pattern-recognition receptors (PRRs)
• Recognize highly conserved structural motifs that
  found within microbial species and not found in
  the host (PAMPs)
• Patterns recognized by PRRs
• Families and location of PRRs

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• Soluble PRRs
• Lipopolysaccharide-binding protein
• Mannose binding protein (MBL)
• C-reactive protein (CRP)
• Cell membrane PRRs
• Scavenger receptors (SRs)
• Location and function
• Toll-like receptors(TLRs)
• Location and function

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