Understanding Antibody Diversity in Immunity

Aug 17, 2024

Lecture Notes: Antibody Diversity and the Immune System

Overview

  • Antibodies are crucial proteins in the immune system.
  • The human immune system requires a vast variety of antibodies to combat diverse pathogens (bacteria, viruses, parasites).
  • Antibodies are proteins consisting of two light chains and two heavy chains.
  • A Nobel Prize-winning discovery explained how the body generates billions of antibodies using only approximately 20,000 genes.

Antibody Production

  • B-cells: Responsible for making antibodies.

    • B-cells have around 20,000 genes like other cells.
  • Rag Enzyme:

    • An enzyme called RAG acts as a DNA shuffler.
    • Targets genes responsible for the antibody binding site.

Gene Segments and Diversity

  • Gene Segments:

    • Three kinds of gene segments: V (Variable), D (Diversity), J (Joining).
    • Heavy Chain Segments:
      • ~130 different V segments.
      • 27 D segments.
      • 6 J segments.
  • DNA Shuffling Process:

    • RAG binds randomly to a J segment and a D segment, removing the DNA between them.
    • Other enzymes join the ends together.
    • Similar process occurs with a V segment.
    • Result: A gene composed of one V, one D, and one J segment.
  • Combination Potential:

    • Over 20,000 possible VDJ combinations for the heavy chain.
    • Light chain adds another 400 possible gene combinations.
    • Combining heavy and light chains results in approximately 8 million possible antibodies, each with a unique binding site.

Additional Diversity

  • During the joining process, extra DNA is added or removed at segment junctions.
  • This increases antibody diversity from millions to billions.

Immune System Capability

  • The vast diversity allows the immune system to respond to novel diseases.
  • Theoretically, one of our antibodies could potentially bind to any target in the universe.

Conclusion

  • The diversity and adaptability of antibodies are key to the immune system's ability to handle countless different pathogens.