Week 5 S - Antibodies

Cells & Immunity Lecture Overview

• Instructor: Phil Knight

• Course Code: BI2BC45

• Week: 5 Lectures

Immune System Overview

• Key Components:

  • Innate Immunity (natural)

  • Adaptive Immunity

    • Humoral Immunity (B cells)

    • Cell-Mediated Immunity (T cells)

• Antibody (Ab):

  • Immunoglobulin (Ig)

  • Binds to antigen (Ag), facilitating Ag elimination

Antigen Definitions and Characteristics

• Definition of Antigen:

  • Any substance, usually foreign, that specifically binds to antibodies or T cell receptors (TCRs)

  • Examples: viruses, bacteria, fungal spores, pollen, mismatched tissue grafts, foreign macromolecules

• Antigenic Determinants (Epitopes):

  • Specific regions on an antigen that interact with the antibody or TCR

  • Usually located on the surface of macromolecules

Immune System Targets

• Pathogens Targeted by the Immune System:

  • Viruses

  • Bacteria

  • Fungi

  • Parasites

Structure and Function of Antibodies

• Basic Structure of Antibody (IgG):

  • Composed of 4 polypeptide chains:

    • 2 identical light chains (~220 AAs)

    • 2 identical heavy chains (~450 AAs)

    • Total MW: ~160 kDa

  • Structure: Fab (antigen-binding fragment) + Fc (constant region)

  • Disulfide Bonds: Link chains together

• Function of Antibodies:

  • Cross-linking polyvalent antigens, leading to agglutination

  • IgG can bind to multiple antigen-binding sites

Antibody Production and Research History

• Key Figures:

  • Gerald Edelman (USA) & Rodney Porter (UK): Nobel Prize for elucidating antibody structure, 1972

• Techniques Used in Antibody Research:

  • Electrophoretic fractionation of serum proteins

  • Use of pepsin and papain to analyze antibody structure

Antigen-Antibody Interactions

• Binding Forces:

  • Ionic interactions

  • Hydrogen bonding

  • Hydrophobic interactions

  • Van der Waals forces

  • Each interaction is reversible, non-covalent, and individually weak but collectively strong

• Affinity vs Avidity:

  • Affinity: Strength of a single binding site

  • Avidity: Overall binding strength considering multiple binding sites

Factors Affecting Antigenicity

• Immunogenicity vs Antigenicity:

  • An immunogen must generate an immune response and typically must be a macromolecule (> 10 kDa)

  • An antigen can bind an antibody but may not produce an antibody (e.g., too small)

• Epitopes:

  • Continuous (linear) epitopes remain intact during denaturation

  • Discontinuous (non-linear) epitopes are affected by denaturation

Generation of Antibody Diversity

• Each individual can generate ~108 different antibody specificities

• Antibodies are encoded by multiple gene segments, with light chains having 3 segments and heavy chains having 4 segments

• Entire antibody repertoire can be generated from a few hundred IG gene segments

Conclusion

• Understanding the immune system, particularly the mechanisms of antibody action, is crucial for comprehending how the body defends itself against disease.