Immunodeficiencies Flashcards
What is artemis a player in?
VDJ recombination and double strand break repair in T and B cells
What causes MHC class I deficiency?
inability of TAP1 to transfer peptides to ER –> no MHC I –> CD8 cell deficiency –> recurrent viral infections
Is common variable immunodeficiency genetic or acquired?
can be both
inherited = defects in B cell formation
acquired = Abs formed against B cells
What 2 types of SCID involve IL-2 signaling?
X-linked and JAK3
What happens in x-linked recessive SCID?
gamma chain of IL-2R is messed up –> T cells can’t help B cells –> SCID
What does low levels of IgG2 cause in children?
poor response to polysaccharid Ags
What is IPEX’s genetic inheritability?
X-linked
What is Wiskott-Aldrich syndrome’s genetic inheritance?
x-linked recessive
What happens in Chediak-Higashi syndrome?
no cathepsin G and elastase in lysosomal granules of leukocytes –> no chemotaxis or granulation
see giant granules in neutrophils
What happens in X-linked lymphoproliferative syndrome?
mutations in gene encoding SAP –> uncontrolled EBV-induced B cell proliferation and CTL activation
defective NK and CTL function and Ab response
What is the most common form of SCID?
gammaC deficiency = 45% of cases
this is x-linked!
What 2 disorders result in self-reactive T cells not being apoptosed?
IPEX and ALPS
How common is ADA-type SCID?
16% of cases are this
What happens in MPO deficiency?
Can’t turn H2O2 into bleach in granules
almost exclusively seen in diabetics
Why are fetuses w/ SCID sometimes miscarried?
they are unable to reject the maternal T cells that cross into fetal circulation in utero
What are the 3 genetic causes of hyper IgM syndrome?
X linked = mutation in CD40L
super rare x linked = mutation in AID
autosomal = CD40 mutation
What two types of SCID are due to issues with VDJ recombination?
RAG1/RAG2
Artemis
What is Chediak higashi syndrome’s genetic inheritance?
autosmal recessive
What are immunodeficiencies w/ defects in Th17 differentiation caused by?
mutations in genes encoding STAT3, IL-17, IL-17R
What is the clinical presentation of variable immunodeficiencies?
reduced levels of IgG, IgA, and often IgM –> poor response to infections
What is the genetic cause of DiGeorge’s syndrome?
deletion of 22q11 chromosome
10=25% of parents have deletion, but are asymptomatic
What do Ab numbers look like in Wiskott-Aldrich syndrome?
low IgM
IgG normal
IgA and IgE elevated
What is the most common phagocytic disorder?
MPO deficiency
What is hyper IgM syndrome in general?
defective b cell heavy-chain class switching --> IgM is the major serum Ab due to absence of CD40-CD40L or AID signaling
How does Wiskott-Aldrich syndrome clinically present?
bleeding and bruising, recurrent infection by encapsulated bacteria
at risk for autoimmune diseases and cancer
What can be mutated in autosomal recessive agammaglobulinemia?
BLNK, Ig-alpha, mu chain, or gamma5 are mutated
What is Wiskott-Aldrich syndrome caused by?
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
What are the key clinical features of DiGeorge’s syndrome?
parathyroid and thymus hypoplasia
malformation of heart outflow
reduction in T cells
hypocalcemia –> can cause tetany or seizures
What is the genetics of G6PD deficiency?
x-linked recessive
What is bare lymphocyte syndrome?
defect in expression of MHC II –> decreased CD4+ T cells –> variable IgA and IgG2 deficiency
What does a deficiency in ADA cause?
buildup of deoxyadenosine –> toxic to T and B cells –> T-, B-, NK- = SCID
What does artemis deficiency cause?
B and T cells can’t mature –> T and B cell deficiencies
What deficiencies is SCID associated with?
T, B, and sometimes NK cell function
What is often the focus of clinical management in DiGeorge’s syndrome?
cardiac defects
What is severe chronic neutropenia?
grp of immunodeficiencies w/ defect in life cycle and anatomy of neutrophils
What is ALPS?
defects in Fas, FasL, caspase-8 or caspase 10 –> no death-inducing signaling complex –> no apoptosis of self-reactive T effector cells
What is the genetic cause of bare lymphocyte syndrome?
genes for MHC II are intact!
mutations are in genes for transcription factors that regulate expression!
What is IPEX?
mutation in FOXP3 –> T regs dont work –> self-reactive T effector cells not eliminated
What is important to know about IgA deficiency?
common
often asymptomatic
disorder of B cell maturation so it can’t secrete IgA
What are defects in Th1 differentiation caused by?
IL-12 or IFN-gamma mutations
What can sometimes cause variable immunodeficiency?
CD19 mutation –> no costimulation for B cell to become activated
What does adenosine deaminase do?
eliminates deoxyadenosine which is generated by DNA breakdown –> prevents toxicity to lymphocytes
What are opportunistic organisms?
pathogens of low virulence that normal people can easily hold in check; invade when host’s guard is lowered (ie immunodeficiency
What is the clinical presentation in autosomal recessive agammaglobulinema?
similar to x-linked
cant get from pre-B to immature B –> severe lack of B cells and secondary lymphoid organ shrinkage
What Ig do many healthy people not have?
IgG4
What happens in x-linked agammaglobulinemia?
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
