Adaptive Antigen Recognition Flashcards
Describe the structure of a B-cell receptor (BCR).
Composed of a surface immunoglobulin (IgM) and two invariant chains (Igα and Igβ).
Describe the structure of the TCR complex.
The TCR itself contains a α:β heterodimer that associates with two CD3 complexes.
What is the difference in diversity mechanisms between BCRs and TCRs?
Somatic hypermutation does not occur in TCRs.
What is the order that the VDJ segments are rearranged in during the combinatorial diversity of the heavy chain?
- D-J
2. V-DJ
What are the roles of RSS and RAG in combinatorial diversity?
RSS: Recombination signal sequences, provides recognition sites for enzymes and ensures gene segments are joined in the correct order.
RAG: Recombination activating genes, encodes for the recombinases needed for combinatorial diversity.
What is the enzyme that catalyzes the addition of nucleotides during junctional diversity?
Terminal deoxyribonucleotidyl transferase (TdT)
What are the two different kinds of nucleotides added during junctional diversity?
P nucleotides: added to asymmetrically cleaved hairpins in a templated manner.
N nucleotides: added in a non-templated manner.
Describe somatic hypermutation.
Point mutations occurring in fully assembled V-J and V-D-J regions during an immune response. Adds to diversity.
What is allelic exclusion?
Inhibition of heavy chain/β chain recombination. Signals from pre-BCR/pre-TCR respectively.
What is the role of stromal cells in B cell development?
Uses VCAM-1/VLA-4 then SCF/Kit to anchor B cell to bone marrow until it is mature enough to be released.
When does alternative splicing of the heavy chain mRNA in B cells occur?
When it recognizes an antigen and begins to proliferate (mature B cell).
When does negative selection occur during B cell development?
When it is an immature B cell.
What happens when an immature B cell recognizes a self antigen?
Development is arrested, but RAG protein synthesis remains on for additional rearrangement of light chain genes. If new light chain is not reactive with self, then B cell will mature. This does NOT occur in T cells.
How does a double-positive thymocyte become a single-positive thymocyte?
The thymocyte will interact with either a HLA I or HLA II. If HLA I, then it will mature into a CD8 T cell. If HLA II, then it will mature into a CD4 T cell.
Describe the stages of thymocyte maturation in the thymus.
In the cortex, thymocytes are differentiated into double-positive thymocytes. Then they are positively selected (self-MHC restricted but may still react to self). Negative selection against self Ag then occurs at the cortico- medullary junction. Mature, self-restricted, self-tolerant, and single-positive T cells then leave the thymus and enter circulation.
