5. Adaptive immunity 2

Question 1

what do ITAMs do?

Answer 1

Transmembrane motifs of BCR and TCR are tiny, so ITAMs allow receptor, once bound to antigen, to generate signalling to intracellular components of the signalling pathway

Question 2

What immunoglobulins are expressed on resting B cells

Answer 2

Resting B cells have IgM and IgD

Question 3

What happens when a resting B cell encounters antigen

Answer 3

Resting B cells have IgM and IgD on cell surface. When encounter an antigen, its stimulates proliferation signal with first signal, second signal and T cell help to ultimately lead to the generation of memory B cells and plasma cells which secrete antibody.

Question 4

What happens to immunoglobulin genes during a B cell’s life?

Answer 4

1. V-region assesmbles from gene fragments
2. Generation of junctional diversity
3. Assembly of transcriptional controlling elements
4. Transcription activated with coexpression of surface IgM and IgG
5. Synthesis changes from membrane Ig to secreted antibodies
6. Somatic hypermutation
7. Isotype switch

Question 5

V(D)J recombination

Answer 5

New gene sequences are produced through V(D)J recombination

Light chain rearrangement is a single step VJ recombination
Heavy chain rearrangement involves a DJ recombination event followed by a VDJ rearrangement

Question 6

V(D)J recombination combinations

Answer 6

44 variable, 27 diversity, 6 joining

3×1011 possible combinations

Question 7

V(D)J recombination steps

Answer 7

1. D to J recombination
2. V to DJ recombination
3. Transcription and splicing
4. Translation and assembly

Question 8

How does rearrangement occur?

Answer 8

Rearrangement occurs between specific sites on the DNA called Recombination Signal Sequences (RSSs)

Rearrangement is catalysed by two Recombination Activating Genes: RAG-1 and RAG-2

Question 9

V(D)J

Answer 9

generation of junctional diversity

RAG complex cleaves the heptamer RSSs from the D and J gene segments to yield DNA hairpins

RAG complex opens hairpins by nicking one strand of the DNA, generating palindromic P-nucleotides

N-nucleotide additions by TdT

Strands pair up

unpaired nucleotides are removed by an exonuclease

gaps are filled by DNA synthesis and ligation to form coding joint

Question 10

Class switch recombination

Answer 10

Same receptor, different constant region
allowing the cell to perform a range of effector functions

Constant regions are spliced out using switch regions located upstream of each constant region
First cut is always just before the Cµ region
The second cut is determined by the cytokines secreted by follicular T helper cells

Question 11

1st class switch step

Answer 11

The first targeted switch region is always the Sµ switch region. The other, partner, switch region is determined by the cytokines present

Question 12

Key enzyme in first step of class switching

Answer 12

Activation induced cytidine deaminase (AID) is the critical enzyme in this process