congenital immunodeficiencies Flashcards
what are B cell definicies
what are examples
often absent or reduced follicles and germinal centers in lymphoid organs
pyogenic bacterial infections, enteric bacterial and viral infections
what are T cell deficiencies? ex?
- reduced T cell zones in lymphoid organs
- reduced dth rxns to common antigens
- defective t cell proliferaiton
ex: viral and intracellular infections (p jroveci, other fungi, nontuberculosis myobacteria)
what are innate immune defiencies? ex?
variable depending on which component of the immune system is active
ex: pyogenic bacterial and viral infections
immunodeficiencies must have these features
chronic, severe, or recurrent
non responsive to antibiotic therapy
microbes may be atypical
what are opportunistic organisms
pathogens with low virulence
may occur when pt is immunocompromised
what is PIDS ? how is it diagnose? types?
primary immunodeficiencies
mainfest in first year of life when baby no longer recieving IgG from mom
diagnosed by recurrent and protracted infections
innate PID: problems with phagocytosis, complement
adaptive pid: problems with B cells, T cells, combined
warning signs of immunodefiency disorder are
8 or more ear infections in one year
2 or more sinus inf in one year
2 or more bouts of pneumonia in one year
2 or more deep seated inf
recurrent abscesses
need for IV to clear infection
opportunistic infections
family history
how do you diagnose different types of PIDS?
recurrent sinopulmonary bacterial infection— screen humoral immunity**
recurrent viral/fungus infection— screen cellular immunity
recurrent skin abscesses/fungal infection— screen for phagocyte defect
bacteria or menigitis with encapsulated bacteria— screen for complement deficiency
**refer to SB for further details
what is CBC used for
screen for T cell, B cell, T/B cell defects
looking for decreased numbers
what is DTH skin test
screen for T cell defects
looking for negative, impaired T cells
what is serum IgG, IgM, IgA
screen for hummoral def
looking for decrease in Ig’s
what is ab testing to specific ag after immunization
screen for humoral def
looking for decrease of ab response to vaccination
what is total hemolytic complement assay
screen for complement def
looking for decrease components of complement
what is nitroblue tetrazolium test
screen for phagocyte disorder
looking for abnormal test result
what is scid? symptoms? how is it diagnosed? treatment?
severe combined immune deficiencies
infants around 4-6 months present with chronic diarrhea, oral thrush, persistent infections, failure to thrive
profound T cell lymphopenia
T cell receptors low/undetectable
treatment is isolation and hematopoietic stem cell transplantation
immuotypes of SCIDS
T- B- NK- : ADA deficiency
T- B- NK+ — artemis gene product defiency or RAG1/RAG2 def
what is artemis?
what happens in def?
symptoms?
enzyme in VDJ recombination and repairs double stranded breaks
T- B- NK+
low IgG, IgA, IgM
rare autosomal recessive radiosensitive SCID
T and B cells markedly decreased but NK cells are normal
symptoms: diarrhea, candidiasis, pneumonia
pts should avoid all live vaccines
what is ADA
what happens in the defiency
Adenosine Deaminase Def
converts toxic (for lymphocytes) deoxyadenosine to harmless deoxyinosine
T- B- NK-
low IgG, IgA, IgM
autosomal recessive
second most common SCID
def leads to accumulation of toxic deoxyadenosine
pts must avoid all live viral vaccines
what is SCIDS? how does it manifest?
profound def of T cells, B cells, NK cells
associated with severe lymphopenia
severe opportunistic infections- chronic diarrhea, failure to thrive
fetus is at risk of abortion due to inability to reject maternal T cells that cross placenta
what is PNP def? sympotoms? treatment?
Purine Nucleoside Phosphorylase def
T- B- NK+/-
normal IgM, IgG, IgA
rare autosomal recessive
accumulation of intracellular dGTP- decreases peripheal T cell numbers
sympotoms are early onset neurological abnormalities
autoimmune disorders are common: hemolytic anemia, thyroid disease, arthritis, lupus
treatment is HSCT
what is RAG1/RAG2 def? genetic trait? causes? symptoms?
T- B- NK+
low IgG, IgA, IgM
autosomal recessive
impaired VDJ recombination that leads to decreased expression of pre-TCR and pre-BCR
symptoms are diarrhea, candidiases, pneumonia
what is omenn syndrome? symptoms?
leaky RAG1/RAG2 allows for partial function
symptoms: severe erythroderma, splenomegaly, eosinophilia, high IgE
what is JAK3? causes? genetic trait?
T- B+ NK+
very low IgG, IgA, IgM
mutation in gene that encodes janus kinase 3
autosomal recessive
boys and girls are equally affected
defect in IL-2 receptor signaling
what is agammaglobulinemia ? causes?
primary form is X linked trait, autosomal recessive form also exists
early B cell development is arrested at pre-B cell stage leading to low circulating B cells
what is BTK def? genetic trait? causes?
bruton tyrosine kinase- progresses pre-B cell to immature B-cell
T+ B- NK+
no IgG, IgM, IgA
X linked
defect in rearrangment of Ig heavy chains
diagnosed in first 5-6 months of life
what are IgG subclass deficiencies? symptoms?
T+ B- NK+
some IgG subclasses low, normal IgM,IgA,IgE
caused by defects in several genes
may be asymptomatic but also may present recurrent viral/bacterial infections in respiratory tract
low levels of IgG2- poor responses to polysaccrhaides ags
IgG4- many healthy people have none
IgA def mechanism? symptoms?
T+ B+ NK+
no IgA, normal IgG, IgM
prevalance higher in males
high incidence- most people are healthy
pathogenic mechanism- IgA secreting B cells have disorders in the maturation/differentiation step
syptoms are recurrent infections, allergies, autoimmune diease
pts with serum anti-IgA IgG respond with anaphlaxis to IVIG transfusion
what is DiGeorge syndrome? cause? symptoms?
selective T lymphocyte immunodef in maturation of T cells- T cell def (complete dgs) or low levels
T- B+ NK+
normal IgG, IgA, IgM
caused by microdeletion of 22q11.2 region
classic triad: cardiac abnormalities, hypocalcemia, hypoplastic thymus
humoral imm intact
pts can have live virus vax
what is hyper IgM syndromes?
T+ B+ NK+
high IgM, low IgG and IgA
group of diseases characterized by impaired Ig class switching and somatic hypermutation
normal levels of peripheral B cells but low numbers of cd27+ memory B cells
X linked HIGM is ? symptoms? genetic trait?
mutation in the CD40Lgene (normally CD40 on B cells binds to CD40L on T cells to causeclass switching and somatic hypermutation)—happens in periphery
increase suspectibility to bacterial infection
2/3 of causes of HIGM
**autosomal CD40 def in males and females cause of 1/3 of HIGM
what is transiet hypogammaglobulinemia of infancy? sypmtoms?
T+ B+ NK+
low IgG, IgA, normal or low IgM
fetus IgG production is delayed for up to 36 months
increased suspebility to sinopulmonary infections
what is CVID? cause? how is it diagnosed? symptoms?
Common Variable Immune Deficiency
T+ B+/- NK+
low IgG and IgA, sometimes low IgM
defect in ab production- associated with hypogammaglobulinemia
B cells dont differentiate in to plasma cells due to mutations in B cell growth factors and co stimulators
diagnosed based on history of recurrent pyogenic sinopulmonary infections after 20-30 years of age (onset begins around 4-5 years)
pts have increased risk of infections, autoimmune diseases, malignancies
autosomal disorder
what are T cell immundodeficiencies
group of disorders caused by problems with growth, maturation, and survival of T cells
can also harm B cells, NK cells
can span infancy to adulthood
suspecible to opportunistis infections, autoimmunity, cancer
what common y chain deficiency
T- B+ NK-
very low IgG, IgA, IgM
most common form of SCID
X linked recessive
def in gene encoding gamma chain thats located in T cell growth factor receptor IL-2Ry (shared with other cytone receptors IL-4, IL-7, IL-19, IL-15, IL-21)
no B cells- T cells cant help- cant produce abs
symptoms: failure to thrive, severe thrush, opportunistic, chronic diarrhea
what is IL-7ra chain deficiency? genetic trait? symptoms? diagnosis?
T- B+ NK+
very low IgG, IgA, IgM
autosomal recessive
IL-7 important in early T cell development
symptoms: candidiases, chronic diarrhea, pneumonia, severe viral infections
diagnosis from sequencing
avoid all live vaccines
what is bare lymphocyte syndrome type II? cause? associated with? symptoms?
CD4T- CD8T+ B+ NK+
no MHC class II on APC’s- causes def in CD4 T cells
genes for MHC II are intact, but mutations in transcription factors that regulate expression
associated with variable hypogammaglobulinameia (IgA and IgG2)
recurrent respiratory, GI, urinary tract infections- frequently to death in early childhood
what is class I def?
caused by mutation in TAP1 molecules
CD8 def, CD4 normal
normal ab production
normal DTH (hypersensitivity)
what are CD3 complex def? trait? symptoms? treatment?
T- B+ NK+
low IgG, IgA, IgM
autosomal recessive
decreased T cells and lymphopenia
ab decreased
FTT, opportunistic infections, chronic diarrhea
HSCT for severe types
what is defect in IFN-y-IL-12 axis ? symptoms?
describe to positive regulatory loop associated
problems in positive regulatory loop
suspectibility to nontuberculosis myobacteria
macrophages and dc’s produce IL-12, which binds to IL-12R on T cells/nk cells, which produce IFN-y, which stimulates macrophages to produce H2O2, TNF-a, and IL-2, starting cycle over again
IL 12- differentitates naive t cells into mature T cells (def leads to primary immunodeficiency- pts cant produce IFN-y which is necessary for fighting off intracellular bacterial infection)
pts also cant produce Th17 which rely on IL-17 which relies on IL-2R
what is Th17 def?
suspebility to chronic candidiasis
impariment of Th17 development due to def in IL-17, IL-17r, STAT1, STAT3, AIRE
associated with hyper IgE syndrome
sympotoms are severe aptoic disease, recurrent staph
what is alps? cause?
autoimmune lymphoproliferativ syndrome
defect in Fas, FasL, caspase 8, caspase 10- leading to resistance of T cells to apoptosis
what is IPEX? cause?
immunodysregulation, polyendocrinopathy, enteropathy X linked syndrome
mutation in FoxP3, which inhibits Treg and cannot inhibit self reactive effector T cells
what is Wiskott Aldrich syndroms (WAS)?
mutated protein called WASP
T- B+ NK-
low IgM, normal Ig, elevated IgA and IgE
X linked disorder
what is NK cell def? what are the two types?
over 40 known types
to be considered NKD pts should have major immunologic abnormalities
caused by mutations in multiple genes
1) classical NKD: absence of NK cells (ex: GATA2 def with NK cell lymphopenia)
2) functional NKD- presence of NK cells with defective activity without NK cell lymphopenia (ex: perforin def)
symptoms include multiple severe or disseminated viral infections including herpesvirus, CMV, HSV
