21 terms

Primary Immunodeficiency Diseases

leukocyte adhesion deficiency (LAD I &II)
1) defect in CD18 (or SleX)
2) leukocyte unable to bind ICAM or Selectins
3) delayed wound healing, recurrent bacterial infections, severe gingivitis, NO pus
4) elevated WBC, flow cytometry for CD18
chronic granulomatous disease
1) defective phagocyte oxidase
2) cannot generate ROS
3) abscesses of skin/liver, lymphadenitis, hepatosplenomegaly, pneumonias, granulomas
4) NBT or flow cytometry for neutrophil activation
chediak-higashi syndrome
1) mutations in LYST
2) lysosomal dysfunction
3) partial oculocutaneous albinism, immunodeficiency, mild bleeding
4) ophthalmologic findings, abnormal granules on blood smear
hereditary angioedema (HAE)
1) mutation in C1 INH
2) unchecked classical complement activation & increased bradykinin leads to capillary leakage
3) acute swelling of deep dermis, subcutaneous or submucosal tissue
4) low CH50, C2, C4 (test C1 INH)
paroxysmal nocturnal hemoglobinuria
1) defect in DAF, CD59, C8 (GPI-linked proteins)
2) uncontrolled complement, lysis of erythrocytes
3) hemolytic anemia (dark urine), pancytopenia, thrombosis
4) flow cytometry for CD59 and CD55
C3 deficiency
1) any defect that causes C3 deficiency
2) inability to form C3a or C3b, defective opsonization, chemotaxis, clearance of immune complexes, MAC formation
3) recurrent pyogenic infections, collagen vascular diseases (lupus)
4) CH50 or AP50 complement test
deficiency in early components of classical pathway
1) deficient in C1,2,4
2) unable to clear immune complexes, or activate B cells with C3d, decreased opsonization (compensate with alt/MBL)
3) increased susceptibility to infection, risk of lupus
4) CH50 or AP50 complement test
deficiency of MAC components
1) deficient in C5b-9
2) unable to lyse microbes
3) recurrent neisseriae infections, severe pyogenic infection in children/neonates
4) CH50 or AP50 complement test
1) most commonly X-linked
2) no T cells, nonfunctional B cells, low Ig levels, no Ab response to vaccines, not thymic shadow
3) at 3-6 mo, FTT, oral/diaper candidiasis, viral & fungal infections, diarrhea, cough, congestion, fevers, absent tonsils/lymph nodes
4) CBC + diff, lymphocyte count, lymphocyte response to mitogens
ZAP-70 related SCID
abnormal T cell receptor signaling, few CD8 with normal or elevated CD4, normal B cells with variable Ig levels
DiGeorge syndrome
1) 22q11.2 deletion, ban development of 3/4th pharyngeal pouches
2) impaired T cell production, variable Ig deficiencies
3) Cong. HD, platal abn., dysmorphic facies, hypoparathyroidism and calcemia, immunodifiency
4) FISH for chromosomal deletion
X-linked agammaglobinemia
1) bruton's tyrosine kinase (btk)
2) no B cell development, small tonsils/LN, low Ig levels, no Ab response to vaccines
3) presents when maternal Abs wane, recurrent pyogenic infections
4) CBC + diff, detect lack of CD19/CD20 B cells
hyper IgM syndrome
1) x-linked defect in CD40L on T cells
2) no isotype switching, elevated IgM low other Ig, diagnosed by 4 years
3) recurrent sinopulmonary infections, liver failure, diarrhea, encephalitis, malignancy
4) CBC + diff, Ig levels, flow Cytometry for CD40L on T cells
Wiskott-Aldrich syndrome
1) x-linked, defect in WASP that regulates actin polymerization, affects cell signals, locomotion, immune synapse formation, apoptosis
2) T cell/platelet defects, small platelets, decreased T cell subsets (CD8), poor Ab response to polysaccharides, low IgM, high IgA/E, variable IgG
3) bruising/bleeding, eczema, infections, diarrhea, thrombocytopenia
4) CBC + diff, Ab levels
class I MHC deficiency (bare lymphocyte syndrome I)
1) defects in TAP genes
2) low CD8 T cells r/t no class I MHC in thymus
3) chronic resp. infections and granulomas
4) CBC + diff, serological HLA typing or flow cytometry
class II MHC deficiency (BLS II)
1) mutations in genes for MHC, no class II expression
2) SCID, low CD4 cells, no T cell mediated responses in vivo, low Ab levels & response to microbes/vaccines
3) recurrent infections - GI, pneumonitis, bronchitis, septicemia, FTT, death by age 10
4) CBC + diff, T cells respond to PHA, flow cytometry
selective IgA deficiency
1) defect unknown
2) low levels of IgA +/- IgG2/4
3) recurrent mucosal infections (GI/resp.), can have anaphylactoid response if transfused
4) CBC + diff, Ab levels
transient hypogammaglobulinemia of infancy
1) defect unknown
2) low IgG/IgA, normalize by 2-6 years, poor response to polysaccharid antigens, normal DTH
3) otitis media, sinusitis, pneumonia manifests ~ 6 months
4) CBC + diff, IgG/IgA levels
hyper IgE syndrome (job syndrome) smote with boils?
1) defective STAT3
2) high IgE levels and eosinophilia
3) eosinophilia, eczema, recurrent skin/lung infections, cold (noninflammatory) abscesses
4) CBC + diff for elevated eosinophils with normal neutrophil and lymphocyte counts
common variable immunodeficiency
1) defect ICOS, B cell maturation or T cell abn. that results in defective isotype switching
2) deficiency in 2 or more Ab classes that persist, low IgG/IgA
3) recurrent bacterial infections from infancy to 40 years
4) CBC + diff, Ig levels
1) mutations in ATM (regulates dsDNA breaks), low lymphocyte count & T/B cell function, dysgammaglobulinemia
2) progressive neurological disease with immunodeficiency
3) recurrent sinopulmonary infection in pt with ataxia and telangiectasia (spider veins), absent thymic shadow
4) CBC + diff, Ab levels + clinical presentation