Immunodeficiencies

Question 1

• defect in BTK tyrosine kinase
• X-linked
• Presents with scant lymph nodes

Answer 1

X-linked (Bruton) Agammaglobulinemia

• Defect in BTK prevents maturation in B cells resulting in an absence of antibodies of all kinds
• Recurrent Bacterial and enteroviral infections after age six months

Question 2

• most common primary immunodeficiency
• decreased IgA with normal IgG and IgM
• increased susceptibility to Giardia

Answer 2

Selective IgA deficiency

Question 3

• usually presents after age 2

- increased risk of autoimmune disease, bronchiectasis, lymphoma and sinopulmonary infections

Answer 3

Common Variable Immunodeficiency

- decrease in all immunoglobulins due to a defect in B-cell differentiation

Question 4

• Absent thymic shadow on CXR

- Tetany, cardiac anomalies, and recurrent viral and fungal infections

Answer 4

DiGeorge Syndrome

Question 5

• Labs show decreased INF-gamma

- Presents with disseminated mycobacterial and fungal infections

Answer 5

IL-12 Deficiency (remember, IL-12 is needed for Th1 differentiation which goes on to activate macrophages)

Question 6

• coarse Facies, staph Abscesses, retained Teeth, increased IgE, Dermatological problems
• Deficiency of Th17 cells due to the STAT3 mutation

Answer 6

Autosomal dominant hyper-IgE syndrome (Job syndrome)

“FATED” nemonic

Question 7

• Absent T-cell response to Candida infection in skin and mucous membranes

Answer 7

Chronic mucocutaneous candidiasis

Question 8

• Baby/child presenting with failure to thrive, chronic diarrhea, thrush and recurrent infections of all kinds
• decreased TRECs
• absent thymus shadow

Answer 8

Severe Combined Immunodeficiency (SCID)

• Most common type is x-linked deficiency in IL-2R gamma chain
• Adenosine deaminase deficiency occurs in males/females (autosomal recessive)

Question 9

• triad of cerebellar defects, superficial blanching nests of capillaries, and IgA deficiency

Answer 9

Ataxia Telangiectasia

• Caused by defect in ATM gene resulting in a failure to detect DNA damage thus allowing cell cycle to continue (NHEJ is defective)
• All antibodies decreased

Question 10

• Severe pyogenic infections early in life and opportunistic infections
• Normal or elevated IgM with all antibodies low

Answer 10

Hyper-IgM Syndrome

• most commonly due to defective CD40L on Th cells —> No class switching
• x-linked therefore “M”ales get hyper Ig”M”

Question 11

• Child presenting with thrombocytopenia, eczema, and recurrent infections
• mutation in WASp gene

Answer 11

Wiskott-Aldrich syndrome (WATER)

• WASp mutation results in platelets and WBCs being unable to reorganize actin cytoskeleton resulting in defective antigen presentation
• high IgE and IgA increase risk of autoimmune disease

Question 12

• Recurrent skin and mucosal bacterial infections with absent pus
• Associated with delayed separation of the umbilical cord

Answer 12

Leukocyte adhesion deficiency (Type 1)

- Absence of neutrophils at infection site due to defect in LFA-1 (CD18) protein—> impaired chemotaxis

Question 13

• Recurrent pyogenic infections by encapsulated organisms
• Albinism
• Peripheral neuropathy
• Histology shows giant granulocytes

Answer 13

Chédiak-Higashi syndrome

- defect in lysosomal trafficking regulator gene prevents formation of the phagolysosome

Question 14

• Increased susceptibility to catalase positive organisms

- Nitroblue tetrazolium dye reduction test fails to turn blue

Answer 14

Chronic Granulomatous Disease

- defect in NADPH oxidase prevents formation of ROS and hence a decrease in respiratory burst in neutrophils