Immunodeficiencies

Question 1

What is artemis a player in?

Answer 1

VDJ recombination and double strand break repair in T and B cells

Question 2

What causes MHC class I deficiency?

Answer 2

inability of TAP1 to transfer peptides to ER –> no MHC I –> CD8 cell deficiency –> recurrent viral infections

Question 3

Is common variable immunodeficiency genetic or acquired?

Answer 3

can be both
inherited = defects in B cell formation
acquired = Abs formed against B cells

Question 4

What 2 types of SCID involve IL-2 signaling?

Answer 4

X-linked and JAK3

Question 5

What happens in x-linked recessive SCID?

Answer 5

gamma chain of IL-2R is messed up –> T cells can’t help B cells –> SCID

Question 6

What does low levels of IgG2 cause in children?

Answer 6

poor response to polysaccharid Ags

Question 7

What is IPEX’s genetic inheritability?

Answer 7

X-linked

Question 8

What is Wiskott-Aldrich syndrome’s genetic inheritance?

Answer 8

x-linked recessive

Question 9

What happens in Chediak-Higashi syndrome?

Answer 9

no cathepsin G and elastase in lysosomal granules of leukocytes –> no chemotaxis or granulation
see giant granules in neutrophils

Question 10

What happens in X-linked lymphoproliferative syndrome?

Answer 10

mutations in gene encoding SAP –> uncontrolled EBV-induced B cell proliferation and CTL activation
defective NK and CTL function and Ab response

Question 11

What is the most common form of SCID?

Answer 11

gammaC deficiency = 45% of cases

this is x-linked!

Question 12

What 2 disorders result in self-reactive T cells not being apoptosed?

Answer 12

IPEX and ALPS

Question 13

How common is ADA-type SCID?

Answer 13

16% of cases are this

Question 14

What happens in MPO deficiency?

Answer 14

Can’t turn H2O2 into bleach in granules

almost exclusively seen in diabetics

Question 15

Why are fetuses w/ SCID sometimes miscarried?

Answer 15

they are unable to reject the maternal T cells that cross into fetal circulation in utero

Question 16

What are the 3 genetic causes of hyper IgM syndrome?

Answer 16

X linked = mutation in CD40L
super rare x linked = mutation in AID
autosomal = CD40 mutation

Question 17

What two types of SCID are due to issues with VDJ recombination?

Answer 17

RAG1/RAG2

Artemis

Question 18

What is Chediak higashi syndrome’s genetic inheritance?

Answer 18

autosmal recessive

Question 19

What are immunodeficiencies w/ defects in Th17 differentiation caused by?

Answer 19

mutations in genes encoding STAT3, IL-17, IL-17R

Question 20

What is the clinical presentation of variable immunodeficiencies?

Answer 20

reduced levels of IgG, IgA, and often IgM –> poor response to infections

Question 21

What is the genetic cause of DiGeorge’s syndrome?

Answer 21

deletion of 22q11 chromosome

10=25% of parents have deletion, but are asymptomatic

Question 22

What do Ab numbers look like in Wiskott-Aldrich syndrome?

Answer 22

low IgM
IgG normal
IgA and IgE elevated

Question 23

What is the most common phagocytic disorder?

Answer 23

MPO deficiency

Question 24

What is hyper IgM syndrome in general?

Answer 24

defective b cell heavy-chain class switching --> IgM is the major serum Ab
due to absence of CD40-CD40L or AID signaling

Question 25

How does Wiskott-Aldrich syndrome clinically present?

Answer 25

bleeding and bruising, recurrent infection by encapsulated bacteria at risk for autoimmune diseases and cancer

Question 26

What can be mutated in autosomal recessive agammaglobulinemia?

Answer 26

BLNK, Ig-alpha, mu chain, or gamma5 are mutated

Question 27

What is Wiskott-Aldrich syndrome caused by?

Answer 27

defect in cytoskeletal protein, WASP = in hematopoietic lineage --> platelets and leukocytes don't develop right, are small, and fail to migrate normally *progressive decrease in t cells

Question 28

What are the key clinical features of DiGeorge's syndrome?

Answer 28

parathyroid and thymus hypoplasia malformation of heart outflow reduction in T cells hypocalcemia --> can cause tetany or seizures

Question 29

What is the genetics of G6PD deficiency?

Answer 29

x-linked recessive

Question 30

What is bare lymphocyte syndrome?

Answer 30

defect in expression of MHC II --> decreased CD4+ T cells --> variable IgA and IgG2 deficiency

Question 31

What does a deficiency in ADA cause?

Answer 31

buildup of deoxyadenosine --> toxic to T and B cells --> T-, B-, NK- = SCID

Question 32

What does artemis deficiency cause?

Answer 32

B and T cells can't mature --> T and B cell deficiencies

Question 33

What deficiencies is SCID associated with?

Answer 33

T, B, and sometimes NK cell function

Question 34

What is often the focus of clinical management in DiGeorge's syndrome?

Answer 34

cardiac defects

Question 35

What is severe chronic neutropenia?

Answer 35

grp of immunodeficiencies w/ defect in life cycle and anatomy of neutrophils

Question 36

What is ALPS?

Answer 36

defects in Fas, FasL, caspase-8 or caspase 10 --> no death-inducing signaling complex --> no apoptosis of self-reactive T effector cells

Question 37

What is the genetic cause of bare lymphocyte syndrome?

Answer 37

genes for MHC II are intact! | mutations are in genes for transcription factors that regulate expression!

Question 38

What is IPEX?

Answer 38

mutation in FOXP3 --> T regs dont work --> self-reactive T effector cells not eliminated

Question 39

What is important to know about IgA deficiency?

Answer 39

common often asymptomatic disorder of B cell maturation so it can't secrete IgA

Question 40

What are defects in Th1 differentiation caused by?

Answer 40

IL-12 or IFN-gamma mutations

Question 41

What can sometimes cause variable immunodeficiency?

Answer 41

CD19 mutation --> no costimulation for B cell to become activated

Question 42

What does adenosine deaminase do?

Answer 42

eliminates deoxyadenosine which is generated by DNA breakdown --> prevents toxicity to lymphocytes

Question 43

What are opportunistic organisms?

Answer 43

pathogens of low virulence that normal people can easily hold in check; invade when host's guard is lowered (ie immunodeficiency

Question 44

What is the clinical presentation in autosomal recessive agammaglobulinema?

Answer 44

similar to x-linked | cant get from pre-B to immature B --> severe lack of B cells and secondary lymphoid organ shrinkage

Question 45

What Ig do many healthy people not have?

Answer 45

IgG4

Question 46

What happens in x-linked agammaglobulinemia?

Answer 46

mutation in BTK gene --> can't get from pre-B cell to immature B cell --> no rearrangement of Ig Heavy chain secondary lymphoid organs are poorly developed bc absence of mature B cells and Igs