More Lecture 1 Flashcards
SLC
Surrogate light chain
Function of surrogate light chain
1)
2)
1) Act as a generic light chain to bind to recombined heavy chain
2) Complex with heavy chain and scaffolding molecules to send ‘success’ signal
What does the IgH-SLC complex with to form pre-BCR?
Ig alpha and Ig beta (heterodimer)
There are two Ig alpha and Ig beta heterodimers
What bears the pre-B cell receptor?
Pre B cell
When does the B cell receptor form?
Immature B
Once light chains combine with heavy chains
What does the B cell receptor complex with the send success signal?
Ig alpha and Ig beta
Function of BLNK protein
Adaptor protein in transduction of pre-BCR success signal
Allows other proteins to bind to it
Function of Bruton’s tyrosine kinase
Signalling molecule in transduction of pre-BCR success signal
What do mutations in Bruton’s tyrosine kinase result in?
~85% of cases of agammaglobulinaemia
Symptoms of agammaglobulinaemia 1) 2) 3) 4) 5)
1) No, or little serum antibodies of any type
2) Functional T cells
3) No B cells
4) Recurrent infections (mostly strep pneumoniae, haemophilus influenzae)
5) Repeated otitis in children, sinusitis in adults
Mean age of agammaglobulinaemia diagnosis
3 years
Why don’t symptoms of agammaglobulinaemia appear at birth?
Antibodies from mother that cross placenta protect baby
Cause of X-linked agammaglobulinaemia
Mutation in Bruton’s tyrosine kinase
Mutations in Bruton’s tyrosine kinase
Over 600 identified
Maintained in population by de novo mutation
No single mutation occurs in over 3% of cases
Symptoms of adenosine deaminase deficiency
No T cells
No B cells
No NK cells
Symptoms of gammaC chain deficiency
No T cells
B cells
No NK cells
Symptoms of JAK3 deficiency
No T cells
B cells
No NK cells
Symptoms IL7R deficiency
No T cells
B cells
NK cells
Symptoms of RAG deficiency
No T cells
No B cells
NK cells
Symptoms of artemis deficiency
No T cells
No B cells
NK cells
Which stage of lymphocyte development does adenosine deaminase allow?
Lymphoid-primed multipotent progenitor to early lymphoid progenitor
Which enzyme allows progression from lymphoid-primed multipotent progenitor to early lymphoid progenitor?
Adenosine deaminase
Which enzymes allow progression from early lymphoid progenitor to T and B cells?
RAG1/2, Artemis
Which step of lymphocyte development do Rag and Artemis allow?
Early lymphoid progenitor to T cell or B cell
Which step of lymphocyte development do gammaC and JAK3 allow?
Early lymphoid progenitor to T cell and NK cell
Which enzymes allow progression from early lymphoid progenitors to NK cells and T cells?
gammaC, JAK3
Which enzyme allows progression from early lymphoid progenitor to T cell?
IL7R
Which step of lymphocyte development does IL7R allow?
Early lymphoid progenitor to T cell
Treatment for agammaglobulinaemia without B cells
Purified IgG from alcohol fractionation of donated blood
Methods of purified IgG delivery
1)
2)
1) 400-600mg/kg once every month
2) 100-150mg/kg self-administered every week
Normal IgG levels
12g/L
Levels of IgG aimed for in treatment
5g/L at trough
Half life of IgG
21 days
Cost of intravenous Ig treatment for agammaglobulinaemia without B cells
$50,000 per year
