Lecture 21: Immune Deficiencies Flashcards Preview

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Flashcards in Lecture 21: Immune Deficiencies Deck (28):

In general patients with primary phagocytic defects are idnetified at a young age on the basis of 

their susceptibility to normally nonpathogenic bacteria or fungi


infections by Catalase-positive microorganisms and Asperigillosis species are characteristic of 

  • Chronic Granulomatous Disease


Infection by Atypical mycobacteria suggest a defect in the 

IFN gamma- IL12 Axis 


Nearly all primary defects of phagocytes result form a mutation that affects 

the innate immune system 


Severe Chronic Neutropenia 

  • Definition:
    • Absolute neutrophil count <500 cells per cubic millimeter 
  • Suppresses inflammation and increases susceptibilty to recurrent and severe bacterial and fungal infections
  • Cause:
    • Mutations in neutrophil elastase gene (ELA2)  



Chronic Granulomatous Disease

  • Chacterized by:
    • Tendency to form granulomas (masses of immune cells that form at sites of infection or inflammation) 
  • Biochemical cause:
    • Enzymatic Deficiency of NADPH oxidase in phagocytes 
      • which results in failure to generate superoxide anion and other ORadicals
  • Susceptibility:
    • to recurrent infection with catalase-positive organisms (e.g. Staphylococci) 
  • More common in males and is most frequent phagocytic primary immunodeficiency 


G6PD deficiency

  • Manifestation:
    • same as chronic granulomatous disease and leads to a tendency to form granulomas
  • Associated with Anemia because G6P is especially important in red blood cell metabolism
  • The lack of substrate for NADPH 
  • X-linked recessive disease


Chediak-Higashi Syndrome

  • Autosomal Recessive disorder
  • Diagnostic criteria
    • Patial albinism (defect in growth of melanocytes) 
    • no NK activity 
  • Moleculular defect:
    • in granule structure (Abnormal Giant Granules in Neutrophils)
    • Granules contain NO cathepsin G and Elastase
  • Defects in:
    • Chemotaxis and degranulation 
  • Biphasic immunodeficiency:
    • First phase
      • Susceptibilty to infection (usually staphylococci and streptococci) (this makes since because Neutrophils no Cathepsin G and Elastase) 
    • Second phase
      • An accelerated Lymphoproliferative syndrome with hepatosplenomegaly and lymphadenopathy
  • Diagnostics:
    • Demonstration of giant azurophilic cytoplasmic inclusions in blood cells 


Leukocyte Adhesion Deficiency (LAD) 

  • Workup:
    • flow cytometic assessment of the neutrophil adhesion molecules CD11 and CD18, the expression of which is absent or decreased on neutrophils (and other leukocytes) 
  • Even with no infection neutrophil count in blood is about twice the normal limit
  • clinical features:
    • history of recurrent infections of the oral and genital mucosa, skin, intestinal and respiratory tracts
    • Delayed detachment of the umbilical cord 
    • Slow wound healing
    • Severe bacterial infefctions ( pneumonia, skin infections, otitis media)
    • Failure to form pus 
    • no neutrophil aggregation 
      • thus no binding to intercellular adhesion molecules on endothelial cells
      • Resuling in infected foci containing few neutrophils, healing slowly, with enlarged borders and dysplastic scars
  • Causes
    • Mutation resulting in Lack of expression of LFA-1 (Lympocyte function-association antigen 1)  
      • (note LFA-1 binds to ICAM-1 (CD54), ICAM-2 (CD102), and ICAM-3 (CD50) 


Abnormalities in the early components of the classical complement pathway (C1,C4, and C2) typically manifest as 

systemic lupus erythematosus-like autoimmunity, but reccurrent sinopulmonary infections are also seen, especially in C2 deficiency 


Defects in ___ produce a clinical phenotype that is indistuishable from an antibody defect, although this complement deficiency is markedly less frequent than humoral immunodeficiencies. 



Alternative complement pathway defects, including Properdin, Factor B and Factor D deficiences also present with 

severe neisserial and other bacterial infections


Defects in the Late components of complement producing defects in the generation of the membrane attack complex (C5-C9) present with increased susceptibility to _______ that might not manifest until adolescence or young adulthood. 

infections with Neisseria species


Factor H deficiency is associated with 

atypical hemolytic uremic syndrome or glomerulonephritis 


C1 esterase inhibitor deficiency causes 

hereditary angiondema


Decay-accelerating factor defects are seen in patients with 

paroxysmal nocturnal hemoglobinuria 


The best screeening test for defects in the classical complement pathway is 

  • total hemolytic complement activity (CH50) assay
    • a classical complement component deficiency will result in virtual absence of hemolysis on CH50 testing
    • In contrast, SLE shows the markedly decreased but not absent results 


The best screening test for defects in the alternative complement pathway is the 

  • AH50 assay 
    • a decreased AH50 test result suggest a deficiency in Factor B, Factor D, or Properdin


A decrease in both CH50 and AH50 test results suggests deficiency in 

a shared complement component (from C3 to C9)