Lecture 21: Immune Deficiencies

Question 1

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

Answer 1

their susceptibility to normally nonpathogenic bacteria or fungi

Question 2

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

Answer 2

• Chronic Granulomatous Disease

Question 3

Infection by Atypical mycobacteria suggest a defect in the

Answer 3

IFN gamma- IL12 Axis

Question 4

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

Answer 4

the innate immune system

Question 5

Severe Chronic Neutropenia

Answer 5

• 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)

Question 6

Chronic Granulomatous Disease

Answer 6

• 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 O₂ Radicals
• Susceptibility:
  
  • to recurrent infection with catalase-positive organisms (e.g. Staphylococci)
• More common in males and is most frequent phagocytic primary immunodeficiency

Question 7

G6PD deficiency

Answer 7

• 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

Question 8

Chediak-Higashi Syndrome

Answer 8

• 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

Question 9

Leukocyte Adhesion Deficiency (LAD)

Answer 9

• 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)

Question 10

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

Answer 10

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

Question 11

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

Answer 11

C3

Question 12

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

Answer 12

severe neisserial and other bacterial infections

Question 13

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.

Answer 13

infections with Neisseria species

Question 14

Factor H deficiency is associated with

Answer 14

atypical hemolytic uremic syndrome or glomerulonephritis

Question 15

C1 esterase inhibitor deficiency causes

Answer 15

hereditary angiondema

Question 16

Decay-accelerating factor defects are seen in patients with

Answer 16

paroxysmal nocturnal hemoglobinuria

Question 17

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

Answer 17

• 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

Question 18

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

Answer 18

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

Question 19

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

Answer 19

a shared complement component (from C3 to C9)

Question 20

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