Immunodeficiencies

Question 1

B-cell disorders

Answer 1

• X-linked (Bruton) agammaglobinemia
• Selective IgA deficiency
• Common variable immunodeficiency

Question 2

T-cell disorders

Answer 2

• Thymic aplasia
• IL-12 receptor deficiency
• Autosomal dominant hyper-IgE syndrome (Job syndrome)
• Chronic mucocutaneous candidiasis

Question 3

B- and T-cell disorders

Answer 3

• Severe combined immunodeficiency
• Ataxia- telangiectasia
• Hyper-IgM syndrome
• Wiskott- Aldrich syndrome

Question 4

Phagocyte dysfunctions

Answer 4

• Leukocyte adhesion deficiency (type 1)
• Chediak- Higashi syndrome
• Chronic granulomatous disease

Question 5

X-linked (Bruton) agammaglobinemia

Answer 5

• defect in BTK–> no B-cell maturation
• recurrent bacterial and enteroviral infections after 6 months (decreased maternal IgG)

Question 6

Selective IgA deficiency

Answer 6

decreased IgA with normal IgG, IgM levels

Question 7

Common variable immunodeficiency

Answer 7

• defect in B-cell differentiation
• decreased plasma cells, decreased immunoglobulins

Question 8

Thymic aplasia

Answer 8

• 22q11 microdeletion (DiGeorge syndrome and velocardiofacial syndrome)
• failure to develop 3rd and 4th pouch
• cardiac defects, abnormal facies, thymic hypoplasia–>T-cell maturation, cleft palate, hypocalcemia (CATCH)
  decreased T cells, PTH, calcium

Question 9

IL-12 receptor deficiency

Answer 9

• decreased Th1 response
• decreased INF-gamma
• disseminated mycobacterial and fungal infections
• present after administrationnof BCG vaccine

Question 10

Autosomal dominant hyper-IgE syndrome (Job syndrome)

Answer 10

• deficiency of Th17–> impaired recruitment of neutrophils
• cold staph. abscesses, retained baby teeth, course facies, dermatologic problems, increased IgE, bone fracture from minor trauma

Question 11

Chronic mucocutaneous candidiasis

Answer 11

• T-cell dysfunction
• defects in AIRE
• persistent Candida albicans
• absent in vitro T-cell proliferation
• absent cutaneous reaction

Question 12

Severe combined immunodeficiency

Answer 12

• defective IL-2R gamma chain
• ADA deficiency
• failure to thrive, chronic diarrhea, thrush
• recurrent infections
  absence of thymic shadow

Question 13

Ataxia- telangiectasia

Answer 13

• defects in ATM
• ataxia
• spider angiomas
• IgA deficiency
• decreased IgA, IgG, IgE

Question 14

Hyper-IgM syndrome

Answer 14

defective CD-40L on Th cells–> class switching defect
- severe pyogenic infections (Pneuocystis, Cryptosporidium, CMV)

Question 15

Wiskott- Aldrich syndrome

Answer 15

• mutation in WAS gene
• leukocytes and platelets unable to reorganize actin cytoskeleton
• thrombocytopenia, eczema, recurrent infections
• increased IgE, IgA

Question 16

Leukocyte adhesion deficiency (type 1)

Answer 16

• defect in LFA-1 integrin
• impaireed migration and chemotaxis
• late umbilical cord separation, absent pus, dysfunctional neutrophils–> recurrent bacterial infections
• absence of neutrophils at infection sites–> impaired wound healing

Question 17

Chediak- Higashi syndrome

Answer 17

• defect in LYST
• microtubule dysfunction in phagosome- lysosome fusion
• progressive neurodegeneration, lymphohistiocytosis, albinism, recurrent pyogenic infections, peripheral neuropathy (PLAIN)
• giant granules
• pancytopenia

Question 18

Chronic granulomatous disease

Answer 18

• defect of NADPH oxidase–> decreased respiratory burst
• increased susceptibility to catalase positive organisms