Primary Immunodeficiencies Flashcards
(47 cards)
Sinopulmonary
Humoral
Viral, fungal
Cellular
Skin abscesses, fungal
Phagocytes
Encapsulated (bacteremia, meningitis; Nisseria)
Complement
Accumulation of lymphocyte toxin deoxyadenosine, unable to convert to deoxyinosine
Avoid all live viral vaccines
SCID: Adenosine-Deaminase (ADA) Deficiency
T-, B-, NK-
Low IgG, IgA, IgM
Autosomal recessive
Presentation with diarrhea, candidiasis, Pneumocystis jiroveci pneumonia
Avoid all live viral vaccines
SCID: Artemis Deficiency
T-, B-, NK+
Low IgG, IgA, IgM
Autosomal Recessive Radiosensitive
SCIDs are characterized by what three things?
severe opportunistic infections, chronic diarrhea, failure to thrive; oral thrush
Accumulation of intracellular deoxyguanosine triphosphate (dGTP); toxic to lymphocytes = decrease in peripheral T cells
Autoimmune disorders: hemolytic anemia, thyroid disease, arthritis, lupus
HSCT definitive treatment
Avoid all live viral vaccines
SCID: Purine Nucleoside Phosphorylase (PNP) Deficiency
T-, B+, NK+/-
Normal IgG, IgA, IgM
Autosomal Recessive
Impaired V(D)J Recombination leading to defective expression of pre-TCR and pre-BCR
Presentation with diarrhea, candidiasis, Pneumocystis jiroveci pneumonia
Avoid all live viral vaccines
SCID: RAG1/RAG2 Deficiency
T-, B-, NK+
Low IgG, IgA, IgM
Autosomal Recessive
Leaky RAG1/RAG2 defects allow partial function, give rise to which atypical form of SCID?
Characterized by severe erthyroderma, splenomegaly, eosinophilia, high IgE
Omenn Syndrome
This SCID causes a defect in IL-2 receptor signaling
SCID: Deficiency of Jak3
T-, B+, NK+
Autosomal recessive
Early B-cell development is arrested at pre-B-cell stage, circulating B cells are absent or present in low concentrations
Agammaglobulinemia
This agammaglobulinemia disease is caused by a defect in rearrangement of the Ig heavy chain genes
X-linked BTK Kinase Deficiency
B-, T+, NK+
No IgG, IgM, IgA
X-linked
This agammaglobulinemia disease is typically asymptomatic, may be associated with recurrent viral/bacterial infections involving the respiratory tract
Isolated IgG Subclass Deficiencies
B-, T+, NK+
Some IgG subclasses low; normal IgM, IgA, IgE
IgG2 – poor response to polysaccharide Ags
B cells may have disorders of maturation or terminal differentiation
serum anti-IgA IgG, risk to develop non-IgE mediated anaphylaxis
IgA Deficiency
B+, T+, NK+
No IgA; normal IgG, IgM
higher in males
Classic triad: cardiac anomalies, hypocalcemia, hypoplastic thymus (leading to T-cell immune dysfunction)
DiGeorge Syndrome (DGS)
T-, B+, NK+
Normal IgG, IgA, IgM
normal numbers peripheral B cells, low numbers CD27+ memory B cells
Hyper IgM Syndromes (HIGM)
B+, T+, NK+
High IgM; low IgG, IgA
characterized by: impaired Ig class switching and somatic hypermutation
What is the cause of X-Linked HIGM?
Mutations in CD40L gene
X-linked CD40L Deficiency is only seen in males! (2/3)
Autosomal CD40 seen in male and female (1/3)
explains characterization of impaired Ig class switching and somatic hypermutation in HIGM
Increased susceptibility to sinopulmonary infections
Transient Hypogammaglobulinemia of Infancy
B+, T+, NK+
Low IgG/IgA; normal-low IgM
majority of pts normalize between 2 and 4 yrs
Characterized by a defect in Ab production associated w/ hypogammaglobulinemia
Diagnosed based on a history of recurrent pyogenic sinopulmonary infections
B cells fail to differentiate into plasma cells
Common Variable Immune Deficiency (CVID)
B-/+, T+, NK+
autosomal disorder
number of circulating B cells reduced or normal
pts increased risk of infections, autoimmune, malignancies
Common y Chain Deficiency (yc or IL-2Ry)
pts present w/ failure to thrive, severe thrush, opportunistic infections, chronic diarrhea
most common form of SCID
X-linked recessive
T-, B+, NK-
v. low IgG, IgA, IgM
gene encodes gamma-chain shared by T-cell growth factor receptor (IL-2Ry) and other growth factor receptors
IL-4, IL-7, IL-9, IL-15, IL-21 share receptor
no functional B cells b/c T cells unable to help
avoid all live viral vaccines
d/t loss of IL playing key role in early T cell development
pt presents w/ candidiasis, chronic diarrhea, pneumocystis jiroveci pneumonia, viral infections
IL-7R alpha chain deficiency
T-, B+, NK+
v. low IgG, IgA, IgM
autosomal recessive
Bare Lymphocyte Syndrome T2 (BLS II): No MHC II on APC causing a deficiency in CD4+ T cells, genes encoding MHC II are intact on chromosome 6. Where is the mutation?
Mutations are in genes which encode for transcription factors that normally regulate the expression of the MHC II genes
CD4 T-, CD8 T+, B+, NK-
Autosomal Recessive
HLA II-negative SCID
variable hypogammaglobulinemia
recurrent respiratory, GI, urinary tract infections
mutation in TAP 1
what cells are deficient and cause recurrent viral infections?
MHC I Deficiency
deficient: CD8+
