Primary Immunodeficiencies Flashcards
What defect would you want to screen for with recurrent skin abscesses/ or fungal infections
Phagocyte defect
MyD88 deficiency
Impaired signaling for all TLRs except TLR3
Recurrent pyogenic bacteria infection
Patients lack fevers and lack elevated levels of ESR/CRP during infection
Low TNF-a, IL-1, IL-6 during infection
DiGeorge syndrome
T-, B+, NK+
T-cell deficiency
Hypoplastic thymus, cardiac abnormalities, hypocalcemia
HIGM
High IgM, low IgG/IgA, T+, B+, NK+
Normal levels of peripheral B cells, low CD27+ memory B cells
Transient Hypogammaglobulinemia of Infancy
Low IgG/IgA, IgM is normal or low
Intrinsic IgG production is delayed for up to 36 months
Increased susceptibility to sinopulmonary infection
C2 deficiency
Most common complement deficiency in caucasion
Found in young kids with recurrent streptococcus pneumoniae
Paroxysmal nocturnal hemoglobinuria
GPI deficiency
DAF and CD59 not linked to membrane
Increased RBC susceptibility to hemolysis
PNP deficiency
Purine nucleoside phosphorylase deficiency
T-, B-, NK+
Accumulation of intracellular dGTP
Early neurological abnormalities
Common to have associated AI disorders including hemolytic anemia, thyroid disease, arthritis, lupus
HSCT is treatment
Agammaglobulinemia
B cell development is arrested at the pre-B cell stage
Circulating B cells are absent or low in number
T+, B-, NK+
CD3 deficiency
T-, B+, NK+, Low IgG, IgA Form of SCID Lymphopenia, decreased T cells Specific Ab response is decreased Failure to thrive, opportunistic inf, diarrhea
NK deficiency- NKD
Classical NKD= Absence of NK cells (GATA2 deficiency)
Functional NKD= Presence of NK cells with defective activity (perforin deficiency)
Recurrent viral infections
Chronic granulomatous disease CGD
Phagocytic disorder, tendency to form granulomas
Deficiency of NADPH oxidase in phagocytes
Cannot generate superoxide anion
Defective elimination of extracellular pathogens
Recurrent inf with catalase positive organisms (staph)
Th17 deficiency
Susceptible to chronic mucocutaneous candidiasis
Mutations in IL-17/IL-17R, TFs- STAT1, STAT3 or AIRE
CD40L deficiency
Responsible for 2/3 of HIGM cases Unable to class switch or activate B cells, no B cell differentiation
SCID
Low IgA, IgG, IgM Severe lymphopenia Severe opportunistic infections At risk of abortion due to inability to reject maternal T cells Avoid all live viral vaccines
ADA deficiency
Second most common cause of SCID
Leads to accumulation of toxins for lymphocytes metabolic by-products deoxyadenosine
ALPS
Defects in Fas, FasL, Caspase-8 or 10 results in abrogated formation of death-inducing signaling complex DISC and resistance of effector T cells to apoptosis
Bare lymphocyte syndrome II
CD4-, CD8+, B+, NK+
No MHC II expression, deficient CD4 cells
Respiratory/GI/UT infections, early death
Common variable immune deficiency CVID
Defect in Ab production, B-/+, T+, NK+
Number of circulating B cells is low or normal
B cells cannot differentiate into plasma cells
Recurrent pyogenic sinopulmonary infections
IL-7R alpha chain deficiency
T-, B+, NK+, IgA/IgG low
Ig levels are low/absent due to absence of T cell costimulatory signaling
Candidiasis, diarrhea, pneumocystis jiroveci pneumonia, severe viral infections
X-linked BTK deficiency
Defect in rearrangement of Ig heavy chains
IgA, IgG, IgM are absent or very low
B-, T+, NK+
Isolated IgG deficiency
Decreased concentration of one or more IgG subclass
Usually asymptomatic, can be associated with recurrent viral/bacterial infections- usually respiratory
B+, T+, NK+
What are you looking for after a failed DTH skin test
T cell defects
Factor H deficiency
Associated with atypical hemolytic uremic syndrome or glomerulonephritis
Leukocyte adhesion deficiency LAD
Neutrophilia (2x normal # even if not currently infected)
Neutrophils are unable to aggregate
Recurrent infection of oral/genital mucosa, intestine, respiratory tract
Few neutrophils able to be transported to sites of inflammation- slow healing, dysplastic scars
Jak3 deficiency
SCID caused by mutation in Jak3
Causes defect in IL-2 receptor signaling
T-, B+, NK-
LAD I-III
LAD I- B2 integrin gene mutation- no B2 integrin
LAD II- impaired adhesive function of PSGL-1
LAD III- impaired signaling of B2 integrin
RAG1/RAG2 deficient SCID phenotype
T-
B-
NK+/-
Leaky RAG1/RAG2 defect can give rise to atypical form of SCID known as Omenn syndrome (high IgE)
ADA deficient SCID phenotype
T-
B-
NK-
Wiskott-Aldrich syndrome WAS
Low IgM, normal IgG, elevated IgA/IgE, T-, B+, NK+
T cell lymphopenia, decreased NK cytotoxicity
Recurrent encapsulated bacterial infections
Viral infection, PJPneumonia/candida
Thrombocytopenia, eczema, cellular/humoral immunodeficiency, AI disease
MHC I deficiency (BLS I?)
Mutation in TAP1 protein
CD8+ cells deficient- recurring viral infections
Normal DTH, Ab production, CD4 cells
Common y chain deficiency (yc or IL-2Ry)
Most common form of SCID, T-, B+, NK-
Low IgG, IgA
IL-2Ry deficient because y chain mutation
No functional B cells since T cells are unable to help
Failure to thrive, thrush, opportunistic infection, diarrhea
Defect in IL-12/IFN-y pathway
IL-12 produced by DCs & MOs stimulates IFN-y release by T/NK cells
Increased susceptibility to nontuberculous mycobacteria
IL-12 essential for differentiation of naïve Th1 cells
Susceptibility to intracellular pathogens and fungal infection
Defective formation of IL-17 producing Th17 cells (hence the fungal infections)
IgA deficiency
B+, T+, NK+
Recurrent infections with encapsulated bacteria
Many times IgM can compensate for loss of IgA
Often develop autoimmune disease & allergy
Possible development of non-IgE mediated anaphylaxis in response to IVIG transfusion
What defect would you screen for in bacteremia or meningitis with encapsulated bacteria
Complement deficiency
IPEX
Self reactive T effector cells are not inhibited because of a mutation in FOXP3 results in loss of inhibition by Treg cells
Artemis deficiency
Rare radiosensitive SCID
T-, B-, NK+
Candidiasis, pneumocystis jiroveci pneumonia
Increased risk for lymphomas
Hereditary angioedema
C1 INH deficiency
Swelling of extremities/lips/face/larynx
Production of bradykinin increased because kallikrein is not inhibited
Primary C1/C4 deficiency
Linked to development of SLE or RA
Large immune complexes are not cleared and form deposits in tissues causing inflammation
G6PD deficiency
Associated with anemia
Lack of substrate for NADPH
Same manifestation as CGD- granulomas
Chediak-Higashi syndrome
Wheelchair bound
Abnormal giant neutrophil granules, defective chemotaxis/degranulation
Response to infection- blunted neutrophilia due to delayed diapedesis
Partial albinism, no NK activity
