Exam 1: L11 Flashcards
(20 cards)
What antibodies do IL-4 inhibit or induce?
- IgM, IgG3, IgG1, IgG2b, IgG2a, IgE, IgA
IgM –> inhibits
IgG3 –> Inhibits
IgG1–> Induces
IgG2b –>
IgG2a –> inhibits
IgE –> induces
IgA –>
What antibodies do IFN-gamma inhibit or induce?
- IgM, IgG3, IgG1, IgG2b, IgG2a, IgE, IgA
IgM –> inhibits
IgG3 –> induces
IgG1–> inhibits
IgG2b –>
IgG2a –> induces
IgE –> inhibits
IgA –>
What antibodies do TGF-beta inhibit or induce?
- IgM, IgG3, IgG1, IgG2b, IgG2a, IgE, IgA
IgM –> inhibits
IgG3 –> inhibits
IgG1–>
IgG2b –> induces
IgG2a –>
IgE –>
IgA –> induces
What antibodies do IL-21 inhibit or induce?
- IgM, IgG3, IgG1, IgG2b, IgG2a, IgE, IgA
IgM –>
IgG3 –> induces
IgG1–> induces
IgG2b –>
IgG2a –>
IgE –>
IgA –> induces
Describe hypervariable regions
Describe the VDJ BCR process (7 steps)
1) RAG (recombination activating genes) 1/2 binds RSS (12/23)
2) RAG endonuclease activity cuts the DNA backbone (ss)
3) Creates a hairpin loop, leaving a double stranded break at the end of RSS
4) Ku70:Ku80 (repair proteins) bind to the DNA hairpin ends
5) DNA-PK: Artemis opens the hairpin at a random site
6) The cut end is modified by TdT adding and removing nucleotides like God
7) two coding ends are ligated by DNA ligase IV in association with XRCC4
8) other direction it could go: Ku70:Ku80 binds DNA ends and DNA ligase IV: XRCC4 ligates the ends
Describe TCR- VDJ process and TCR structure
- composed of alpha and beta chains or gamma delta (MCH restricted, except gamma delta)
- constant region provides structural support and associates with CD3 proteins, which have ITAM motifs to convey intracellular signals
- TCR beta and gamma loci contain D (diversity)… like heavy chain
- somatic recombination occurs during T cell development in the thymus
- Repeat BCR-VDJ 7 steps
What are the stages of a B Cell?
How does a B cell traverse?
Name the stages of the B cell in relation to gene rearrangement
1) Early pro- B —> rearrangement of DJ (both heavy chains)
2) Late pro-B –> V to DJ rearrangement ( VDJ- on one heavy chain…one chromosome )
3) Large pre-B cell –> has a complete reagrrages VDJ and will proliferates to become small resting pre-B cells
4) Small resting pre-B cells –> re-expresses RAG protein
5) Small pre-B cells re-expressing RAG proteins –> start to rearrange the light chain genes (VJ- repeated rearrangements of unused gene segments on the same allele can occur; unlimited)
6) Immature B cell –> have a heavy and light chain ( light chain paired with a mu chain), complete IgM molecule on cell surface
7) Mature B cell –> produce delta and mu heavy chain, marked by additional IgD on the surface
Describe allelic exclusion in relation to BCR
only one of the two alleles of a gene is expressed to prevent different antigen specificities
What happens when the VDJ rearrangement is in frame?
- happens when productive rearrangement takes place (heavy chain)
- then 2 mu chians with other chains make up the surrogate light chain
- whole complex called pre- b cell receptor
Describe central tolerance
Test if B cells are reactant to self-antigens in the central lymphoid organ (bone marrow)
- The tolerance produced in this stage is called central tolerance
Why might a pre-B cell die due to VDJ rearrangement?
1) DJ rearrangement occurs on both heavy chain
But
2) VDJ happens on only one heavy chain… if the frame is not aligned, will try it VDJ rearrangement on other heavy chain
3) If the proteins are still not aligned ( nonfunctional proteins- out of frame mRNA that encodes stop codons)…. Pre-cell dies
How can self-reactive B cells become non-reactive? (receptor editing)
- by changing their antigen specificity
- if RAG is still expressed, they can rearrange the light chain
- can form a new receptor with the new light chain and old heavy chain
What can happen to B cells in the spleen? (testing for peripheral tolerance)
- occurs after immature B cell migrate from the bone marrow to the spleen (now transitioning B cells)
- Autoreactive–> apoptosis
- low affinity, non-cross-linking –> mature B cell
- no self-reaction–> mature B cell
Why do most transitional B cells die?
- high competition to get to follicle in spleen; if it doesn’t get into one, it dies
- must complete maturation inside of a follicle of the spleen where they receive maturation and survival signals
- survival signal ex… follicular dendritic cell BAFF and B cell BAFF-R stimulation
- Some B cells become marginal zone B cells
- others are follicular B cells
What rapid response does marginal B cells have?
blood-born antigens or pathogens
What’s B1B cell’s story?
- from fetal liver
- self renewal in the peritoneal and pleural cavities
- activated in a T cell independent fashion
pg 14
