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.