Immunodeficiencies Flashcards
X-linked agammaglobulinemia (Bruton agammaglobulinemia)
Defect in BTK, a tyrosine kinase, no B-cell maturation
Only in boys (XLR)
Recurrent bacterial and enteroviral infection after 6 mo (maternal IgG is protective)
Find: no B-cells in blood, few Igs of any class, scanty LNs and tonsils; don’t give live vaxx
Selective IgA deficiency
Unknown origin (most common 1˚ immunodeficiency)
Mostly asymptomatic; airway, GI infection, autoimmune disease with atopy and anaphylaxis to IgA containing products
Low IgA, normal IgG/M; susceptible to Giardia
Common variable immunodeficiency
Defect in B-cell differentiation
Presents after 2yo or further delayed, increased risk of autoimmune disease, bronchiectasis, lymphoma, sinopulmonary infection
Few plasma cells and few Igs
Thymic aplasia (DiGeorge syndrome)
22q11 deletion; no 3rd/4th pharyngeal pouches so no thymus or parathyroids
Leads to tetany (hypocalcemia), recurrent viral and fungal infections, conotruncal abnormalities (tetralogy of Fallot, patent truncus arteriosus)
Find: low T cells, low PTH, low Ca, absent thymic shadow on CXR
IL-12-R deficiency
Decreased Th1 response (AR)
Mycobacterial and fungal infections, may present after admin of BCG vaccine
Low IFN gamma
Autosomal dominant hyper-IgE syndrome (Job syndrome)
Deficiency of Th17 cells due to STAT3 mutation leads to poor recruitment of neutrophils
FATED: course facies, cold stapholococcal abscesses, retained primary teeth, high IgE, derm (eczema), bone fx
High IgE/eos
Low IFN-g
Chronic mucocutaneous candidiasis
T cell dysfunction
Non-invasive candida infections of skin and mucous membranes
Absent in vitro T-cell prolif with candida
Absent cutaneous rxn with exposure
Severe combined immunodeficiency
Multiple causes including:
IL-2-R gamma chain defect (most common, XLR)
Adenosine deaminase deficiency, AR)
Failure to thrive, chronic diarrhea, recurrent viral, bacterial fungal and protozoal infections
Tx: avoid live vaxx (MMR/Varicella) Salk, etc.
Give antimicrobial prophylaxis and IVIG
BM transplant is curative, no rejection possible!
Find: low T-cell-R exicision circles (TRECs), absent thymic shadow, germinal centers in LNs or T-cells on flow cytometry
Ataxia telangectasia
Defect in ATM gene (dsDNA break repair) cell cycle arrest
Triad: cerebellar defects (ataxia), angiomas, IgA def.
Find: high AFP
low IgA/G/E
Lymphopenia, cerebellar atrophy
high risk of lymphoma and leukemia
Hyper-IgM syndrome
Defective CD40L on Th cells leading to class switching defect XLR
Severe pyogenic infections early in life, opportunistic infections (Pneumocystis, Cryptosporidium, CMV)
Nl or high IgM
Very low A/E/G
No germinal centers
Wiskott-Aldrich syndrome
Mutation in WASp gene; leukocytes and platelets can’t reorganize cytoskeleton, defective Ag-presentation XLR
Thrombocytopenia, exzema, recurrent infections, risk of autoimmune d/o and malignancy
Low to normal G/M
High E/A
Few and small platelets
Leukocyte adhesion deficiency (type 1)
Defect in LFA-1 integrin (CD18) on phagocytes, impaired migration and chemotaxis AR
recurrent skin and mucosal bacterial infections, absent pus, impaired wound healing, delayed separation of umbilical cord
Chédiak-Higashi syndrome
Defect in lysosomal trafficking regulator gene (LYST); MT dysfunction in phagosome/lysosome AR
Recurrent pyogenic inf. by staph./strep. partial albinism, peripheral neuropathy, progressive neurodegen., infiltrative lymphohistiocytosis
Giant granules in granulocytes and platelets, pancytopenia
Mild coag defects
Chronic granulomatous disease
Defect of NADPH oxidase so no ROS and no respiratory burst in neutrophils XLR
Susceptible to catalse +
Abnl flow cytometry for dihyrdrorhodamide
Nitroblue tetrazolium dye reduction test fails to turn blue
