BC - L2 Flashcards
Topics?
Distribution of lymphocytes Immune response early stages of B & T cell activation Activities with the GC HIGM CVID
Describe B cell development in terms of location
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Describe the distribution of lymphocytes
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possible reasons for a failure to respond to an infection?
no B-lymphocytes (agammaglobulinaemia w/o B-cells)
no CD4 T-lymphocytes (severe combined immunodeficiency)
no B or T lymphocytes (severe combined immunodeficiency)
no signal from the CD4 to the B Cell
failure of the B cell to respond to T-cell signals
failure of the B cell to respond antigen
immune response and memory response to a protein antigen?
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early stage of B & T cell activation?
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Activities within GC?
proliferation (T cell driven) isotype switching somatic hypermutation affinity maturation memory formation
Describe isotype switching (including layout of heavy gene)
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Role of AID (how it works)?
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What targets AID to specific S regions?
T cell derived signal IL-4
Why make IgM and then change to IgG?
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Describe somatic hypermutation
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How does AID initiate somatic hypermutation?
converting cytosines in DNA to Uracil within IgV Genes, at both H and L chain loci
U is recognised as foreign in DNA by enzyme UNG (uracil N- glycosylase) and removed, creating a gap that is repaired by Base Excision Repair involving an error-prone Pol
the U/G mismatch is repaired by mismatch repair (MMR) pathway involving MSH2/6 (mismatch recognition heterodimer), mismatch Exonuclease 1 and error-prone Pol
U is not removed but replicated over = passive mutation
Describe the B-T cell help pathway
List possibel defects
blocking the NFkB pathway blocks:
B-cell proliferation
class switching and V gene mutation (no AID)
defects in AID and DNA repair also block CSR and SHM
Molecular basis of hyper-IgM immunodeficienies?
CD40L (CID) CD40 AID AID-cter UNG NFkB signalling
