Flashcards in Nelson- Immunodeficiency syndromes Deck (45)
What is the difference between primary and secondary immunodeficiencies? and what populations do they effect?
Primary--almost all geneticall determines (congenital) affect those 6 mos - 2 yrs
Secondary- d/t complications of cancer, infection, malnutrition, immunosuppression, radiation or chemo
What do primary immunodeficiencies affect?
T or B cell functions in adaptive immunity (75% of cases)
Defense mechanisms in innate immunity
How are primary immunodeficiencies detected?
multiple recurrent infections
What are B cell disorders?
Key features: brutons
Mutated tyrosine kinase (Btk)
Failure of pre-b cells to become MATURE B cells
Clinical features of brutons?
• Typical presentation: sinopulmonary (SP) infections (pharyngitis, otitis media, bronchitis, and pneumonia) to Haemophilus
• Susceptible to certain GI viruses (enterovirus)
• Often have persistent Giardia infection (no IgA in GI)
Why does Brutons often present at 6 mos?
Maternal Ab protects from birth to 6 mos than Ig decreases
What do you see in the peripheral blood of someone w/ brutons?
Decrease/absent B cells and gammaglobulins
No plasma cells
What is the treatment for brutons?
prophylactic Ig therapy
Key features: common variable immunodeficiency?
Defect in B-cell maturation to plasma cells
Adult disorder--both sexes affected equally
Common clinical sxs of CVI?
Sx similar to agammaglobulinemia:
SP infections (90-100%),
What is seen in the blood of someone w/ CVI?
decreased gammaglobluin production
What are the two forms of CVI and how is it diagnosed?
sporadic and inherited
dx of exclusion
Key features: IgA def
Failure of IgA B cells to mature into plasma cells
Increases susceptibility to SP infections and diarrhea
Familial or acquired
Clinical features of IgA def?
• Decreased serum and secretory IgA levels
• Decreased IgA → weaken mucosal defenses → increased SP infxns and diarrhea (Giardia)
• Particularly prone to infxns if IgG2 and IgG4 deficient
Key features: hyper-IgM syndrome?
• Defect in Ig class switching (Unable to make IgG, IgA and IgE but can make IgM)
• ~70% have X-linked recessive mutation in gene encoding CD40L (T cell cannot activate B cells)
• Others have defect in activation-induced deaminase enzyme (AR inheritance)
What is seen in labs of someone w/ hyper IgM syndrome?
normal to elevated levels of IgM but no IgA, IgE, and very low IgG; peripheral blood shows normal # of T and B lymphocytes
What illnesses does someone w/ hyper-IgM syndrome have?
• Recurrent pyogenic infections
• If CD40L mutation → pneumonia (Pneumocystis jiroveci)
• Increased risk: IgM induced cytopenias (autoimmune hemolytic anemias, thrombocytopenias, neutropenia)
What type of disorder is DiGeorge syndrome?
T cell disorder
Key features: DiGeorge syndrome?
• Failure of 3rd and 4th pharyngeal pouches to develop
• Thymus and parathyroid glands fail to develop → deficiency in cell-mediated immunity
• D/t delection of gene on chrom 22q11 (~90% pts)
• Susceptible to fungal, viral, pneumocystis jirveci infections
What clinical features are associated w/ DiGeorge syndrome?
• Hypoparathyroidism (tetany)
• Absent thymic shadow on radiograph
• Danger of GVH rxn
• Congenital defects of heart and great vessels, facial abnormalities
What is seen in the peripheral blood of some one w/ DiGeorge syndrome?
• Low levels of T lymphocytes in peripheral blood
• T cell areas in spleen and lymph nodes depleted
What diseases are combined B and T cell disorders?
Wiskott Aldrich syndrome
Chediak HIgashi syndrome
What are the two defects that lead to SCID?
X-linked mutation in gene encoding γ-chain subunit of cytokine receptor (50-60%) → T cell development impaired → B cell # decreases b/c no T helpers
Autosomal recessive adenosine deaminase (ADA) deficiency (15%) → accumulation of deoxyadenosine (toxic to B and T cells)
What are the clinical features of SCID?
• Profound defects in both humoral and cell mediated immunity
• Extremely susceptible to recurrent, severe infections
What is seen in infants w/ SCID?
Infants: thrush, extensive diaper rash, failure to thrive
What is the tx for combined B and T cell disorders?
bone marrow transplant
What is the defect associated w/ Wiskott aldrich syndrome? Inheritance?
Mutation in Wiskott-Aldrich syndrome protein (WASP) → variable loss of cell-mediated immunity
Progressive deletion of B and T cells
X-linked recessive disorder
What is the sx triad for wiskott aldrich syndrome?
eczema, thrombocytopenia, SP infections
Increased risk for hodgkin B cell lymphoma