Immunodeficiencies

Question 1

X-linked (Bruton) Agammaglobulinemia defect

Answer 1

• -X linked
• -Defect in BTK (tyrosine kinase gene)
• -B cell deficiency–> low levels of all immunoglobulins
• -Recurrent bacterial infections after 3-6 months

Question 2

Selective IgA deficiency

Answer 2

• -Most appear healthy
• -Sinus and lung infections, atopy, asthma
• -1/600 European descent
• -Possible anaphylaxis to blood transfusions and blood products
• -Most common immunodeficiency

Question 3

Common variable immunodeficiency

Answer 3

• -Defect in B-cell differentiation
• -Increased risk of autoimmune disease, bronchiectasis, lymphoma, sinopulmonary infections
• -Can be acquired in 20’s-30’s
• -Decreased plasma cells and decreased immunoglobulins

Question 4

Thymic aplasia (Digeorge syndrome)

Answer 4

• -22q11 deletion
• -Failure to develop 3rd and 4th pharyngeal pouches–> absent thymus and parathyroids
• -No thymus–> no mature T cells
• -No parathyroids–> Decreased PTH–> Hypocalcemia and tetany
• -Recurrent viral, fungal, and protozoal infections
• -Congenital defects in heart/great vessels

Question 5

IL-12 receptor defeciency

Answer 5

• -Decreased Th1 response.
• -Autosomal recessive
• -Recurrent mycobacterial and fungal infections.
• -Decreased IFN-gamma

Question 6

Autosomal dominant hyper IgE syndrome (Job syndrome)

Answer 6

• -STAT3 mutation–> impaired differentiation of Th17 cells, impaired recruitment of neutrophils
• -High levels of IgE and eosinophils
• -Eczema, recurrent cold S. aureus abscesses, coarse facial features (broad nose, prominent forehead, deep-set eyes, and “doughy” skin
• -Common to have retained primary teeth
• -Increased IgE and decreased IFN-gamma

Question 7

Chronic mucocutaneous candidiasis

Answer 7

• -T cell dysfunction
• -Noninvasive candida albicans infections of skin and mucous membranes
• -Absent in vitro T-cell proliferation in response to candida antigens.
• -Absent cutaneous reaction to candida antigens.
• -Rx: ketoconazole

Question 8

IPEX syndrome

Answer 8

• -Immune dysregulation
• -Polyendocrinopathy
• -Enteropathy
• -X-linked
• -FOXP3 mutation

Question 9

Severe combined immunodeficiency (SCID)

Answer 9

• -Defect in early stem cell differentiation
• -Adenosine deaminase deficiency (AD) defect OR
• -Defective IL-2R gamma chain OR
• -Other gene defect
• -Severe recurrent infections, chronic diarrhea, failure to thrive!
• -No thymic shadow on newborn X-ray.
• -Low/absent CD3+ T cells and hypogammaglobinemia

Question 10

Ataxia-telangiectasia

Answer 10

• -IgA deficiency and T cell deficiency
• -Sinus and lung infections
• -Cerebellar ataxia and poor smooth pursuit of moving target with eyes
• -Telangiectasias (after age 5)
• -Radiation sensitivity
• -Increased risk for lymphoma and acute leukemias
• -Elevated AFP (after 8 mths age)
• -Ave. age of death: 25
• -Decreased IgA, IgG, and IGE

Question 11

Wiscott-Aldrich Syndrome

Answer 11

• -WAS mutation
• -T-cells can’t recognize actin cytoskeleton
• -X-linked recessive
• -Decreased to normal IgG and IgM.
• -Increased IgE and IgA
• -Fewer and smaller platelets
• -Thrombocytopenia, eczema, recurrent pyogenic infections

Question 12

Hyper-IgM Syndrome

Answer 12

• -Increased IgM, all other Ab isotypes decreased
• -Caused by no CD40 on B cells (AR) OR
• -no CD40L on T cells (x-linked; most common)
• -Severe pyogenic infections early in life and opportunistic infections
• -Lymphoid hyperplasia

Question 13

Chronic granulomatous disease*

Answer 13

• -X-linked
• -Defect of NADPH oxidase –> phagocytes can’t destroy catalase + organisms –> very susceptible to S. aureus and aspergillus
• -Diffuse granuloma formation and severe bacterial and fungal infections
• -Diagnosis: Negative nitroblue tertrazolium test or abnormal dihydrorhodamine test
• -Rx: Prophylactic TMP-SMX and itraconazole, IFN-gamma

Question 14

Chediak-Higashi Syndrome

Answer 14

• -Defective LYST gene
• -Defective phagocyte lysosomes–> giant cytoplasmic granules in PMNs (diagnostic)
• -Partial albinism, recurrent respiratory tract and skin infections, neurologic disorders)

Question 15

Leukocyte-Adhesion Deficiency (Type 1)

Answer 15

• -Defect in LFA-1 integrin (CD18 protein) on phagocytes, impaired migration and chemotaxis
• -Autosomal recessive
• -Delayed separation of umbilical cord, recurrent bacterial skin and mucosal infections, absent pus formation, impaired wound healing
• -Increased neutrophils (can’t get into tissues)
• -Absence of neutrophils at infection sites