Antigen and Antigen Receptors

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Antigen and Antigen Receptors

• Lecture 5

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Immune Response is Antigen-Driven
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Immunogen- Substance capable of generating a
specific immune response and binding to immune
components

• Bacterial
• O antigens of Salmonella
• Flagellin
• Toxins
• Viral
• Viral capsid proteins
• Viral envelope glycoproteins

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Antigen

• Substance capable of binding specifically to
  immune components.

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Haptens

• Low mw molecules.
• Antibiotics, drugs
• Not immunogenic, unless...

HAPTENS
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Haptens

• Low mw molecules.
• Not immunogenic, unless...
• conjugated to high mw compounds (carriers) to
  gain immunogenicity

CARRIER
HAPTENS
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• What affects Immunogenicity ?

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Chemical Families
Immunogenic?

• Proteins almost always
• Carbohydrates potentially
• glycoproteins usually
• Lipids poorly
• Nucleic Acids poorly

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Requirements for Immunogenicity

• High molecular weight
• lt1000D-Not Immunogenic (penicillin)
• 1000-6000D May or May not be immunogenic
  (insulin)
• gt6000D-Generally immunogenic (albumin, Tetanus
  toxin)
• Chemically complex
• homopolymers not generally immunogenic
• Ex Polylysine-30,000 D, Poly-D-Glutamic
  acid-50,000D
• Degradable
• Foreignness

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Foreignness
Bovine albumin-specific Immature Lymphocyte
Response to Immunization
Bovine albumin
NO
Apoptosis
No Tetanus Toxoid Antigen
Yes
Toxoid-Specific Immature Lymphocyte
Mature Lymphocyte
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Foreignness
Response to Immunization
NO
Cow
Bovine Albumin
Yes
Sheep
Chicken
Yes
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Immunogenicity

• Antigen
• Dose
• Low Zone Tolerance
• High Zone Tolerance
• Route of Admn.
• SCgtIPgtIVgtIntragastric

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Low-Zone and High-Zone Tolerance
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Enhancing Immunogenicity

• Administration of Protein in Adjuvants.
• Incomplete Freunds adjuvant-oil-in- water
  emulsion
• Complete Freunds adjuvant-oil-in-water emulsion
  plus dead Mycobacteria
• Aluminum hydroxide gel

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Adjuvants-Mode of Action

• Delayed Release-Prolonged Antigen Persistence
• Enhance Costimulatory Signals
• Induce Granuloma formation
• Stimulates Lymphocytes Nonspecifically

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Antigen Receptors

• Recognition of Antigen by Lymphocytes

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Cell Surface Immunoglobulin

• Antigen Receptor on B Cells

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B Cell Antigen Receptor Cell Surface
Immunoglobulin
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B Cell Antigen Receptor
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T Cell Receptor

• Antigen Receptor on T Cells

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Antigen Recognition by Lymphocytes
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B Cell Antigen Recognition

• Via Surface Immunoglobulin
• Recognize and bind FREE ANTIGEN IN SOLUTION
• B Cells bind Native Protein Antigen

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Antigen Recognition By B Lymphocytes
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B Cell Antigen Recognition
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What do B cells recognize in the antigen?

• Epitopes-Antigenic Determinant
• Discrete Sites on the Macromolecule

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B Cell Epitope

• Portion of Ag that binds receptor
• Antigenic determinant
• 5-22 amino acids
• Multideterminant Ags have many different
  epitopes on the same molecule

binding site
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B Cell Epitope

• Continuous/Linear-Single polypeptide segment.
• Conformational/Discontinuous-Amino acids from
  different parts of the Sequence brought together
  by Protein folding.

binding site
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Binding of Antigens