Lecture 12 - The Antibody Paradox

Question 1

List the isotypes of antibodies and their functions

Answer 1

IgG
- secondary response antibody, neutralises toxins, involved in opsonisation
IgA
- protects mucous membranes (secreted into tears, saliva, mucous)
IgM
- primary response antibody, fixes complement
IgE
- protects against parasites ,involved in allergies
IgD
- acts as B cell receptor

Question 2

Describe the different parts of an antibody molecule and give the function for each

Answer 2

• Heavy chain: area near hinge involved in complement activation, ends are involved in antigen binding
• Light chain: lower half near hinge is involved in complement activation, ends are involved in antigen binding
• Constant region: beginning of constant region involved in complement activation
• Variable region: Contain hypervariable regions where the amino acid sequence is very different between different antibodies (complementary determining regions, allow for specific binding to antigen)
• Fc portion: where phagocytic cells
  bind

Question 3

Why is it important to have antibody diversity?

Answer 3

• Antibodies are very specific, and many are needed to protect our bodies from millions of different antigens

Question 4

What is allelic exclusion?

Answer 4

Allelic exclusion is a process by which only one allele of a gene is expressed while the other allele is silenced

Question 5

Give a brief description of somatic recombination.

Answer 5

Somatic recombination is an alteration of the DNA of a somatic cell that is inherited by its daughter cells

Question 6

What enzyme facilitates somatic recombination?

Answer 6

• Recombination Activating Gene (RAG)
– Cuts at RSS
– Loops out section
– Re-combination of genes
– Two RAG-1 and RAG-2

Question 7

Apart from somatic recombination what other mechanisms contribute to antibody diversity?

Answer 7

– P-region nucleotide insertions
• Palindromic (P) sequences found at V region junctions, generated by hairpin loops

– N-region nucleotide additions
• Up to 15 nucleotides can be inserted into the junctions of gene segments by the terminal deoxynucleotidyl transferase (TdT) enzyme

Question 8

Why can’t our genome code for the range of antibodies needed?

Answer 8

• Antibody diversity cannot be generated by germ line cells and must be generated by somatic cells
– New antibody specificities are created during life

Question 9

List the stages of B cell development with reference to antibodies

Answer 9

• Stem cell (no surface Ig)
• Early pro-B cell (no surface Ig)
• Late pro-B cell (no surface Ig)
• Large pre-B cell (u chain temporarily at surface as part of pre-B cell receptor, mainly intracellular)
• Small pre-B cell (intracellular u chain)
• Immature B cell (IgM expressed on cell surface)
• Mature B cell (IgD and IgM made from spliced H-chain transcripts)

Question 10

What do the terms “clonal deletion” and “clonal selection” mean?

Answer 10

Clonal deletion: Removal of B cells that have surface Ig that react to self antigens in bone marrow

Clonal Selection: Activation and proliferation of B cells that react with foreign antigen in the periphery