Nelson- Immunodeficiency syndromes Flashcards
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)
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
What is seen in the blood of someone with wiskott aldrich syndrome?
Decreased IgM
normal IgG
increased IgA and IgE
What is the defect in chediak higashi syndrome? Inheritance?
Mutation in CHS1/LYST (member of vesicle trafficking regulatory protein family) → defective fusion of phagosomes and lysosomes in phagocytes → increased susceptibility to infxn
autosomal recessive
What are the clinical features of chediak higashi syndrome?
Recurrent pyogenic infections albinism progressive neurologic abnormalities mild coagulation defects
How do you dx chediak higashi syndrome?
giant cytoplastmic
granules in leukocytes and
platelets (but confirmed w/
genetic testing)
What are the clinical features of immunodeficiency diseases associated w/ the early classical complement pathway?
Little or no increase in susceptibility to infections but increased incidence of an SLE-like autoimmune disease
What are the clinical features of immunodeficiency diseases associated w/ the alternate pathway (properdin and factor D)?
pyogenic infections (rare)
What are the clinical features of immunodeficiency diseases associated w/ C3 (classical and alternative)?
susceptibility to serious and recurrent pyogenic infections
increased immune complex-mediated glomerulonephritis
What are the clinical features of immunodeficiency diseases associated w/ the terminal components of the complement pathway (C5-C9)?
Recurent neisserial infections d/t impaired MAC function
What are the common causes of secondary immunodeficiency?
Immunosuppressive meds Microbial infection Autoimmune disease Severe burn injury Radiation, toxic chemicals asplenia/hyposplenism aging
What type of infection are pts w/out a spleen at risk for and why?
Loss of splenic macrophages after splenectomy>
increased risk of bacterial infection w/ encapsulated organisms
(S. Pneumonia, H.influena, N. meningitides)
What are the three ways that one could suspect that a pt has immunodeficiency?
Clinical hx
pt presents w/ signature opportunistic infection (pneumonia, prolonged/severe oral candidiasis, invasive aspergillus)
Repeated infections or suggestive sxs
What are the initial labs you would order to assess B cell funciton, T cell function and phagocytic function and complement?
CBC w/ diff- decrease in lymphocytes/neutrophils
blood chemistries (CMP)- diabetes, kidney, liver disease
urinalysis- renal disease
sed rate, CRP- inflammmatory state
Labs for antibody deficiencies are assessing…
B cell function
Ig levels
Flow cytometry and skin testing are assessing…
T cell function,
cutaneous delayed-type hypersensitivity response (if do skin testing w/ candida Ag)
CBC
peripheral smear
genetic tests, specific tests of neutrophil function
are assessing…
Phagocytic disorders (giant azurophilic granules in neutrophils, eosinophils, and other granulcytes indicate Chediak-Higashi syndrome)
Total serum complement (CH50) assesses…
Complement activity
