Week 5 Study Questions Flashcards
Every individual synthesises enormous numbers of different Ig molecules, but the number of genes encoding the various domains in Ig molecules is relatively small, diversity being partly achieved by the rearrangement of which genes?
- H chain variable region comprises: VH (variable), DH (diversity) and JH (joining) gene segments.
- L chain variable region comprises: VL and JL gene segments
There are multiple gene segments in each of these categories in the…?
Germ line
What happens to the different Ig regions during B cell differentiation?
During B cell differentiation, VH -> joins DH -> joins JH -> encode the V region of the H chain.
Similar rearrangements occur for the L chain gene segments
How are primary RNA transcripts made?
- Primary RNA transcripts are made from the rearranged DNA of the H- and L-chains
- non-coding RNA is spliced out and the mRNA is translated
What are the resulting chains after alternative H chain splicing?
splicing of primary transcript results in either a µ or δ chain
What is the significance of allelic exclusion?
Allelic exclusion ensures a B cell produces an Ig of a single antigenic specificity
How is diversity in Ig molecules achieved?
- junctional diversity (imprecise joining)
- somatic hypermutation (class-swithcing)
How is the diversity in T cell receptors different to immunoglobulins?
T cell receptor diversity is achieved in a fashion similar to that of immunoglobulin, but there is no somatic hypermutation
What are the different classes of T cell receptors?
- There are two classes of the T cell receptor α:β receptor and the γ:δ receptor. Cells are
committed to the different lineages depending on the gene rearrangements made - The β, γ and δ-chain genes rearrange simultaneously and if a γ:δ receptor is made first the cell is committed to that lineage
How is B-chain rearrangement involved in T cell proliferation?
If a β-chain gene rearranges productively first the β-chain is involved in forming the
pre-T-cell receptor → cell proliferation and expression of CD4 and CD8.
When is the machinery of rearrangement re-activated?
Proliferation stops and machinery of rearrangement is re-activated and now targets the α-chain gene as well as γ and δ-chain genes
How is lineage commitment determined?
Lineage commitment at this stage is determined by the expression of either γ:δ or α:β receptors on the cell surface
What is the role of thymocytes? What happens if they do not fulfil their role?
If thymocytes fail to make successful gene rearrangements they die by apoptosis
What is the outcome of positive selection of α:β T cells?
- +ve selection of α:β T cells by cortical epithelial cells in the thymus: α:β T cells that bind to a self-MHC molecule survive.
- Recognition of either peptide: MHC class I or MHC class II determines whether the double +ve T cell will become a CD4 or a CD8 T cell.
What is the outcome of negative selection of α:β T cells?
–ve selection by DCs and macrophages eliminates T cells with a T cell receptor that binds too strongly to self peptides complexed with self-MHC class I molecules – stops auto-reactivity
