B3.039 - Immune Cell Development Flashcards
AID Deficiency
defects in activation induced cytidine deaminase (AID) or uracil DNA glycosylase (UNG) lead to increased susceptibility to pyogenic infections only
CD40 and the IL-4 receptor on B cells is ligated by CD40 ligand to do what
AID is transcribed and translated to produce AID
AID deaminates cytidine in what type of DNA and what happens
ssDNA, converts cytidine at the switch sites to uridine which is not normally there
Damaged DNA is recognized and repaired by endonucleases, excising the damaged region resulting in what
class switching
what deficiency is involved in somatic hypermutation in B cells
AID deficiency
describe AID deficiency
production of higher affinity antibodies as the immune response progresses, during activation point mutations are introduced into the DNA that encodes Ig variable region
describe positive selection
Abs that compete for antibody binding the best receive stronger signals is the cell surface antigen receptor leading to increased proliferation
describe negative selection
those Abs with lower affinity do not receive signals to proliferate and will undergo apoptosis
Describe X linked Hyper IgM syndrome
CD40 and CD40L gene defect leading to increased susceptibility to both pyogenic and opportunistic infections
what is SCID
syndrome caused by mutations in different genes whose products are necessary for T/B/NK cell development
how do you diagnose SCID
recurrent episodes of diarrhea, pneumonia, otitis, sepsis and cutaneous infection. Think: Opportunistic infections
what are clinical features of SCID
small thymus
few thymocytes
lacks hassalls corpuscles
Fails to descend from neck (thymus)
what is considered lymphopenic
<4000
what is indicated for infants with abnormal lymphocyte counts
Flow cytometry and T cell functional studies
what is one indicator of maternal T cell engraftment
greater predominant of either CD4 and CD8
what is CD4RO
maternally engrafted cells with memory phenotype
what are CD45RA
normal infant T cells that are naive
what is X linked SCID
T-B+NK-
defect on X chromosome encoding the cytokine receptor subunit common gamma chain
how is X linked SCID diagnosed
IL2 RG diagnosed on flow cytometry
what is gamma c also involved in
growth hormone receptor signaling
how do you tell the difference between X linked SCID and .a recessive JAK-3 deficiency
by the presence of tyrosine - phosphorylated STAT5 by flow cytometry after IL-2 stimulation indicates a functional IL-2/JAK-3 signal transduction pathway
treatment for X linked SCID
HLA identical or haploidentical donor bone marrow transplantation needed for survival
IVIg is often needed
the common gamma chain cytokine receptor subunit is needed for signaling for:
IL2, IL4, IL7, IL9, IL15, IL21
what is autosomal recessive SCID
RAG1, RAG2 mutations
what is ADA deficiency
T-B-NK-
Accumulation of adenosine, 2’-deoxyadenosine and 2’-O-methyladenosine
what do 2’-deoxyadenosine and 2’-O-methyladenosine do
lead directly or indirectly to apoptosis of thymocytes and circulating lymphocytes
which type of SCID has more profound lymphopenia than other SCID types
ADA deficiency (T-B-NK-)
how is ADA treated
HLA identical or haploidentical T cell depleted bone marrow transplantation
Enzyme replacement with PEG-ADA
What is a JAK3 deficiency
T-B+NK-
downstream cytokine signaling issue, not a problem with TCR activation
what is an IL-7 receptor alpha chain deficiency
T-B+NK+
IL-7 receptor alpha is specific only for T cell development
what are RAG-1 and RAG-2 SCIDs
T-B-NK+
involved in VDR rearrangement of T and B cell antigen receptors
what is Omenn syndrome
aka Leaky SCID
RAG-1 and2 can present this way
Generalized erythroderma and desquamation, diarrhea, hepatosplenomegaly, hypereosinophilia and elevated IgE
