Immunology - Congenital immunodeficiencies

Question 1

X-linked recessive disease that causes a complete deficiency of mature B cells, mainly in boys

Answer 1

X-Linked (Bruton) agammaglobulinemia

Question 2

3-6 month old boy with hypoplasia of tonsils and lymph nodes, recurrent, severe, pyogenic infections (pneumonia, otitis media), especially with encapsulated bacteria

Answer 2

X-Linked (Bruton) agammaglobulinemia

Question 3

Absent or low levels of B cells marked by CD19, CD20 and CD21 and low immunoglobulins of all classes, with normal or high T cells

Answer 3

X-Linked (Bruton) agammaglobulinemia

Question 4

Live vaccines are contraindicated in patients wtith

Answer 4

X-Linked (Bruton) agammaglobulinemia

Question 5

Sinusitis, respiratory infections, chronic diarrhea, associated with atopy and anaphylactic reactions to blood products containing IgA.

Answer 5

Selective IgA deficiency

Question 6

The 5 A’s of Selective IgA deficiency

Answer 6

1. Asymptomatic
2. Airway infections
3. Anaphylaxis to IgA containing products
4. Autoimmune disease
5. Atophy

Question 7

Presents in a 20-40 year old with recurrent pyogenic respiratory infections and low levels of IgG, IgA and IgM with normal levels of B and T cells

Answer 7

Common variable immunodeficiency

Question 8

Primary immunodeficiency with low serum levels of all immunoglobulins despite phenotypically normal B cells (B cells are unable to differentiate into Ig-producing cells)

Answer 8

Common variable immunodeficiency

Question 9

Syndrome characterized by defective development of the third and fourth pharyngeal pouches leading to hypoplastic thymus and parathyroids

Answer 9

DiGeorge syndrome (22q11.2 deletion syndrome)

Question 10

Recurrent viral, fungal and PCP pneumonia infections due to T-cell deficiency

Answer 10

DiGeorge syndrome (22q11.2 deletion syndrome)

Question 11

CATCH-22 acronym

Answer 11

C - cardiac abnormalities
A - anomalous face
T - thymic aplasia/hypoplasia
C - cleft palate
H - hypocalcemia
22 - chromosome 22

Question 12

What are the cardiac abnormalities in DiGeorge syndrome?

Answer 12

• conotruncal abnormalities (tetralogy of Fallot or persistent truncus arteriosus)
• ventricular septal defect (VSD)
• atrial septal defect (ASD)

Question 13

What are anomalous face characteristics in DiGeorge syndrome?

Answer 13

• prominent nasal bridge
• hypoplastic wing of the nose
• dysplastic ears
• micrognathia/retrognathia

Question 14

Autosomal dominant STAT3 mutation causing a defect in neutrophil chemotaxis

Answer 14

Hyperimmunoglobulin E syndrome (Job syndrome)

Question 15

Coarse facies, recurrent cold abscesses, recurrent bacterial (staph) infections, retained primary teeth, Hyper IgE, eosinophilia, severe eczema

Answer 15

Hyperimmunoglobulin E syndrome (Job syndrome)

Question 16

FATED acronym for Job syndrome

Answer 16

F - facies and fractures
A - abscesses (cold)
T - teeth retained
E - IgE, eosinophilia
D - dermatologic (severe eczema)

Question 17

Numerous genetic mutations resulting in the defective development of functional B and T cells

Answer 17

• Severe combined immunodeficiency (SCID)

Question 18

Normal at birth, severe, recurrent infections (bacterial diarrhea, chronic candidiasis, viral and protozoal infections), failure to thrive, chronic diarrhea, absent lymph nodes and tonsils

Answer 18

Severe combined immunodeficiency (SCID)

Question 19

Associated with absent thymic shadow on Xray

Answer 19

• DiGeorge syndrome
• SCID

Question 20

X-linked recessive condition caused by impaired function of T cells and thrombocytopenia primarily in males

Answer 20

Wiskott-Aldrich syndrome (WAS)

Question 21

What is the classic triad of Wiskott-Aldrich syndrome?

Answer 21

• purpura (bleeding diathesis)
• eczema
• recurrent opportunistic infections with encapsulated organisms in the first years of life

Question 22

WisPER acronym

Answer 22

W - Wiskott-Aldrich syndrome
P - purpura
E - eczema
R - recurrent infections

Question 23

Normal or low IgG and IgM, increased IgE and IgA, thrombocytopenia and small platelets

Answer 23

Wiskott-Aldrich syndrome

Question 24

Prognosis of Wiskott-Aldrich syndrome

Answer 24

• shortened life expectancy
• increased risk of autoimmune disease and heme malignancies (lymphoma or leukemia)

Question 25

Syndrome characterized by CD40 ligand deficiency causing a B cell class-switching defect

Answer 25

Hyper-IgM syndrome

Question 26

Recurrent severe pyogenic infections since childhood with opportunistic sinopulmonary infections, cryptosporidium enteritis, CMV hepatitis and failure to thrive

Answer 26

Hyper-IgM syndrome

Question 27

Autosomal recessive disease caused by mutation of the ATM gene resulting in severe humoral immunodeficiency (decreased IgA, IgG and IgE), ataxia due to cerebellar atrophy, and capillary malformations.

Answer 27

Ataxia telangiectasia

Question 28

Deficiency of superoxide production by PMNs and macrophages

Answer 28

Chronic granulomatous disease

Question 29

Defective phagocytic NADPH oxidase that results in defective reactive oxygen species production and impaired ability to deactivate or kill ingested microorganisms in the phagocyte.

Answer 29

Chronic granulomatous disease

Question 30

Recurrent, severe infections with catalase-positive organisms, lymphadenopathy and granulomas of the skin and GI/GU tract.

Answer 30

Chronic granulomatous disease

Question 31

Tests used to diagnose chronic granulomatous disease

Answer 31

- dihydrorhodamine test (DHR) - nitroblue tetrazolium dye reduction test

Question 32

What life-long antibiotic prophylaxis do patients with chronic granulomatous disease require?

Answer 32

TMP-SMX for catalase positive infections

Question 33

What therapy reduces the incidence of serious infections in patients with chronic granulomatous disease?

Answer 33

IFN-gamma therapy

Question 34

Autosomal recessive condition characterized by a defect in leukocytic chemotaxis that results in decreased phagocytic activity

Answer 34

Leukocyte adhesion deficiency type 1

Question 35

Absence of the ___ leukocyte adhesion surface molecule LFA-1 (CD18) prevents leukocytes from migrating to tissues during infection or inflammation

Answer 35

beta 2 integrin

Question 36

Recurrent non-suppurative bacterial skin and mucosal infections, impaired wound healing, omphalitis, delayed separation of the umbilical cord ( > 30 days)

Answer 36

Leukocyte adhesion deficiency type 1

Question 37

Leukocytosis with absence of neutrophils at site of infection

Answer 37

Leukocyte adhesion deficiency type 1

Question 38

Autosomal recessive defect in the lysosomal trafficking regulator (LYST) gene resulting in defective neutrophil chemotaxis and microtubule polymerization causing defective phagosome-lysosome fusion

Answer 38

Chediak-Higashi syndrome

Question 39

Recurrent pyogenic infections, partial albinism, progressive degeneration of neurons and peripheral neuropathy

Answer 39

Chediak-Higashi syndrome

Question 40

How is Chediak-Higashi syndrome diagnosed?

Answer 40

Peripheral smear showing giant cytoplasmic granules in granulocytes and platelets

Question 41

A life threatening syndrome of immune activation that results in widespread inflammation and tissue destruction due to increased activity of cytotoxic T cells and macrophages with pancytopenia.

Answer 41

Hemophagocytic lymphohistiocytosis (found in Chediak-Higashi syndrome, and as a complication of infection of mononucleosis)

Question 42

ALPINe acronym

Answer 42

A - albinism L - lymphohistiocytosis P - peripheral neuropathy I - infections N - neurodegeneration; neutropenia