B3.039 - Immune Cell Development

Question 1

AID Deficiency

Answer 1

defects in activation induced cytidine deaminase (AID) or uracil DNA glycosylase (UNG) lead to increased susceptibility to pyogenic infections only

Question 2

CD40 and the IL-4 receptor on B cells is ligated by CD40 ligand to do what

Answer 2

AID is transcribed and translated to produce AID

Question 3

AID deaminates cytidine in what type of DNA and what happens

Answer 3

ssDNA, converts cytidine at the switch sites to uridine which is not normally there

Question 4

Damaged DNA is recognized and repaired by endonucleases, excising the damaged region resulting in what

Answer 4

class switching

Question 5

what deficiency is involved in somatic hypermutation in B cells

Answer 5

AID deficiency

Question 6

describe AID deficiency

Answer 6

production of higher affinity antibodies as the immune response progresses, during activation point mutations are introduced into the DNA that encodes Ig variable region

Question 7

describe positive selection

Answer 7

Abs that compete for antibody binding the best receive stronger signals is the cell surface antigen receptor leading to increased proliferation

Question 8

describe negative selection

Answer 8

those Abs with lower affinity do not receive signals to proliferate and will undergo apoptosis

Question 9

Describe X linked Hyper IgM syndrome

Answer 9

CD40 and CD40L gene defect leading to increased susceptibility to both pyogenic and opportunistic infections

Question 10

what is SCID

Answer 10

syndrome caused by mutations in different genes whose products are necessary for T/B/NK cell development

Question 11

how do you diagnose SCID

Answer 11

recurrent episodes of diarrhea, pneumonia, otitis, sepsis and cutaneous infection. Think: Opportunistic infections

Question 12

what are clinical features of SCID

Answer 12

small thymus
few thymocytes
lacks hassalls corpuscles
Fails to descend from neck (thymus)

Question 13

what is considered lymphopenic

Answer 13

<4000

Question 14

what is indicated for infants with abnormal lymphocyte counts

Answer 14

Flow cytometry and T cell functional studies

Question 15

what is one indicator of maternal T cell engraftment

Answer 15

greater predominant of either CD4 and CD8

Question 16

what is CD4RO

Answer 16

maternally engrafted cells with memory phenotype

Question 17

what are CD45RA

Answer 17

normal infant T cells that are naive

Question 18

what is X linked SCID

Answer 18

T-B+NK-

defect on X chromosome encoding the cytokine receptor subunit common gamma chain

Question 19

how is X linked SCID diagnosed

Answer 19

IL2 RG diagnosed on flow cytometry

Question 20

what is gamma c also involved in

Answer 20

growth hormone receptor signaling

Question 21

how do you tell the difference between X linked SCID and .a recessive JAK-3 deficiency

Answer 21

by the presence of tyrosine - phosphorylated STAT5 by flow cytometry after IL-2 stimulation indicates a functional IL-2/JAK-3 signal transduction pathway

Question 22

treatment for X linked SCID

Answer 22

HLA identical or haploidentical donor bone marrow transplantation needed for survival
IVIg is often needed

Question 23

the common gamma chain cytokine receptor subunit is needed for signaling for:

Answer 23

IL2, IL4, IL7, IL9, IL15, IL21

Question 24

what is autosomal recessive SCID

Answer 24

RAG1, RAG2 mutations

Question 25

what is ADA deficiency

Answer 25

T-B-NK-

Accumulation of adenosine, 2’-deoxyadenosine and 2’-O-methyladenosine

Question 26

what do 2’-deoxyadenosine and 2’-O-methyladenosine do

Answer 26

lead directly or indirectly to apoptosis of thymocytes and circulating lymphocytes

Question 27

which type of SCID has more profound lymphopenia than other SCID types

Answer 27

ADA deficiency (T-B-NK-)

Question 28

how is ADA treated

Answer 28

HLA identical or haploidentical T cell depleted bone marrow transplantation
Enzyme replacement with PEG-ADA

Question 29

What is a JAK3 deficiency

Answer 29

T-B+NK-

downstream cytokine signaling issue, not a problem with TCR activation

Question 30

what is an IL-7 receptor alpha chain deficiency

Answer 30

T-B+NK+

IL-7 receptor alpha is specific only for T cell development

Question 31

what are RAG-1 and RAG-2 SCIDs

Answer 31

T-B-NK+

involved in VDR rearrangement of T and B cell antigen receptors

Question 32

what is Omenn syndrome

Answer 32

aka Leaky SCID
RAG-1 and2 can present this way
Generalized erythroderma and desquamation, diarrhea, hepatosplenomegaly, hypereosinophilia and elevated IgE