Immunodeficiencies Flashcards
B cell disorders
Bruton Agammglobulinemia (X-linked) Selective IgA deficiency Common Variable Immunodeficiency
Bruton agammaglobulinemia- defect
X-linked
Defect in BTK (tyrosine kinase): prevent B cell maturation
Bruton agamma- S&S
Recurrent bacterial (and enteroviral) infections (after 6 mo- when mom’s IgG is depleted)
Absent, scanty lymph nodes
Decreased level of all Igs
Selective IgA deficiency- defect
Unknown, but most common primary immunodef
Selective IgA def- S&S
5 A’s
Recurrent mucosal infections (GI- Giardia)
Majority Asymptomatic, but may affect Airways, Anaphylaxis (with blood transfusion), Autoimmune dz, Atopy (allergy- e.g. eczema, rhinitis, asthma)
Decreased level of IgA
Combined Variable Immunodeficiency- defect
Lots of causes; defect in B-cell differentiation
Causes decreased Igs and plasma cells
CVID- S&S
Can be acquired; often see in 20s-30s
Increased risk of autoimmune diseases (despite the decrease in Igs), lymphoma, bronchiectasis, and sinopulmonary infections
T cell disorders
Thymic aplasia (diGeorge)
IL-12 receptor deficiency
Hyper-IgE (Job) Syndrome
Chronic mucocutaneous candidiasis
Thymic aplasia (diGeorge)
Failure of “Thyrd” and 4th pharyngeal pouches to develop (causes lack of thymus and parathyroids) –> absent thymic shadow (also seen in SCID)
Underlying chr 22q11 deletion (detected by FISH)
Thymic aplasia- S&S
Recurrent viral/fungal infections
Decreased T-cells, PTH, and Ca2+
Other S&S: tetany (hypocalcemia), conotruncal abnormalities (tetrallogy of Fallot, truncus arteriosus),
IL-12 receptor deficiency- defect
Decreased Th1 response (also have decreased IFN gamma- normally produced by Th1 cells to activate macrophages)
Autosomal recessive
IL12-receptor deficiency- S&S
Disseminated mycobacterial and fungal infections (may present after BCG vaccine)
Hyper-IgE (Job) Syndrome- defect
Deficiency of Th17 (due to mutation in STAT3) –> impairs neutrophil/ macrophage recruitment to infection site (because can’t produce proper cytokines like IFN-gamma)
Hyper-IgE (Job) Syndrome- S&S (FATED)
Any kid (girl/boy) w/: FATED Facies (coarse) Abscesses (staphylococcal) Teeth (retained) E- increased IgE Dermatologic probs (Eczema)
Chronic mucocutaneous candidiasis-defect and S&S
T-cell dysfunction (many causes) –> absent T cell response to Candida antigens
Non-invasive Candida infection (in mucosa and skin)
B cell and T cell disorders
SCID (severe combined immunodeficiency)
Ataxia-Telangiectasia
Hyper-IgM
Wiskott-Aldrich
SCID- defect
Many causes, but two main mutations:
IL-2R gamma chain deficiency (X-linked)
Adenosine Deaminase deficiency (AR)
SCID- S&S
Recurrent infections (bacterial, viral, fungal, and protazoal) Failure to thrive, chronic diarrhea, thrush
SCID- dx
Absent thymic shadow (also seen in diGeorge)
Absent germinal centers (lymph node biopsy)
Absent T cells (flow cytometry)
Decreased T cell receptor excision circles (indicate maturation of T cells)
SCID- tx
Bone marrow transplant (no concerns about potential graft rejection by host- because there are no B/T cells)
Ataxia-telangiectasia- deficit
Mutation in ATM gene –> failure to repair dsDNA breaks –> causes cell-cycle arrest
Ataxia-telangiectasia- S&S
Triad: Ataxia (cerebellar Atrophy), spider Angiomas, IgA (and IgG and IgE) deficiency (recurrent mucosal infections)
Hypersensitivity to ionizing radiation