case studies- T cell development Flashcards
Why was the number of CD8+ T cells in Tatiana and her brother decreased despite normal levels of CD4+ cells?
Issue in MHC Class I peptide loading ability, TAP needed for MHC class I to transport peptides to ER to be loaded – leads to no MHC I expression
- repeated viral infections due to mutated TAP2 (not the MHC molecules themselves) …TAP1 and TAP2 form transporter dimer- without either one, no function – nothing to select MHC I now (CD8)
Tatiana had normal DTH responses to tuberculin and Candida. Is this surprising in view of their CD8 deficiency?
No, DTH is related to CD4 T cell response, she has strong CD4 cohort
Genetic defects have also been found in the gene encoding TAP1. Do you think the clinical course in those patients would differ from that observed in Tatiana?
No, the patients with TAP1 deficiency should clinically resemble those with TAP2 deficiency
Why did Helen lack CD4 T cells in her blood?
she has a broad MHC Class II deficiency (didn’t express HLA-DQ or HLA-DR)…not a problem with HLA-DP, may be why she had some level of CD4
Why did Helen have a low level of immunoglobulins in her blood?
- CD4 T cells help make different isotypes of antibody- interaction of B and T cells mediated by CD40/CD40L, leading to AID
- So without CD4, wont have this
- Hyper IgM- low IgG, low IgA, high IgM
If a skin graft were placed on Helen’s arm, do you think she would reject the graft?
Yes, she has normal CD8 function, but lacks CD4 – CD8 mediates tissue rejection
haploytypes are ___, meaning all the same MHC alleles or ___, meaning different at numerous MHC loci
syngeneic
allogeneic
allogeneic response is mediated by ___ cells, which causes…
CD8
tumor and transplant rejection (cytotoxic)
What can cause loss of HLA-DP, DQ, DR?
CIITA deficiency- CIITA is a TF required for expression of MHC II genes
