Nelson- Immunodeficiency syndromes Flashcards
(45 cards)
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?
Brutons
CVI
IgA def
Hyper-IgM syndrome
Key features: brutons
X-linked recessive
Male
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%), GI infections, pneumonia, autoimmune diseases malignancy
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?
SCID
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)
