Primary Immunodeficiency

Question 1

What mutation causes Leukocyte Adhesion Deficiency 2? Why?

Answer 1

Mutation in GDP-fructose transporter that inhibits leukocyte rolling due to decreased ligand expression for selectins. Causes distinct facial features, hypotonia, retardation, recurrent infections

Question 2

What is the clinical presentation of SCID?

Answer 2

Chronic diarrhea, diaper rash, failure to thrive, oral Candidiasis, recurrnt infections, lesions, oppotunistic infections

Question 3

A patient is diagnosed with Common Variable Immunodeficiency. What types of infections are they at increased risk of acquiring? Why?

Answer 3

Increased risk of sinopulmonary infections, autoimmune diseases, and malignancies because of a deficiency in plasma cell production causing low Ig levels

Question 4

A mother reports to the clinic with her 2-year-old son, who is diagnosed with his fourth fungal infection since birth. The mother also reports child is not growing as quickly as her other children. You notice hypotonia and unique facial features. What immunodeficiency may this child have? How can you test for the immunodeficiency?

Answer 4

Leukocyte Adhesion Deficiency 2 - Flow cytometry for CD15

Question 5

A patient has a mutation in the common gamma chain that impairs cytokine signaling. What is the immunodeficiency? What is the immunological presentation?

Answer 5

X-Linked SCID - impaired maturation of B, T, & NK cells

Question 6

A mother gives birth to a healthy appearing newborn. A few months later, the infant becomes ill and is diagnosed with SCID. The mother asks why the diagnosis was not made at birth.

Answer 6

Newborns have less exposure to pathogens during the early part of their life. They also have some protection from the mother’s IgG & IgA (when breastfed) antibodies. Because of this, babies with SCID may appear healthy.

Question 7

What are the three types of Severe Combined Immunodeficiency?

Answer 7

X-Linked SCID, Adenosine Deaminase Deficiency, RAG Deficiency

Question 8

Patients with Bare Lymphocyte Syndrome 2 are at increased susceptibility to what types of infections?

Answer 8

Respiratory, gastrointestinal, urinary tract infections

Question 9

A patient is diagnosed with a mutation in STAT3 that is causing their immunodeficiency. What is the immunodeficiency? What are the immunological and clinical presentations?

Answer 9

Job Syndrome

Deficient Th17 response, impaired neutrophil recruitment, high eosinophils, high IgE

Coarse facies, abscesses, retained teeth, increased IgE, eczema, bone fractures

Question 10

A patient is diagnosed with ADA SCID. What is the immunological presentation?

Answer 10

Deficiency in the adenosine deaminase of the purine synthesis pathway causes a buildup of toxins and reduced B & T cell numbers

Question 11

What is the age of onset and inheritance patter of Chediak-Higashi syndrome?

Answer 11

Onset during infancy or childhood. Autosomal recessive inheritance

Question 12

What is the inheritance pattern of leukocyte adhesion deficiency 2?

Answer 12

Autosomal Recessive

Question 13

What is DiGeorge Syndrome? What is the clinical presentation?

Answer 13

A deletion of 22q11 that results in incomplete development of the thymus and low T cell count. Clinical presentation includes - cardiac defects, abnormal facial features, thymic hypoplasia, cleft palate, hypocalcemia

Question 14

How does the inheritance pattern of the SCID types differ?

Answer 14

X-Linked = X-Linked
ADA & RAG = Autosomal Recessive

Question 15

What immunodeficiency is caused by a defect in the NADPH oxidase that inhibits superoxide formation? How would a patient with this immunodeficiency present?

Answer 15

Chronic Granulomatous Disease - recurrent infections with catalase + bacteria and granuloma formation

Question 16

A mutation in the Bruton Tyrosine Kinase causes what immunodeficiency? How?

Answer 16

X-linked Aggamaglobulinemia - BTK is required for B cell maturation beyond a pre-B cell. The result is no immunoglobulins, no circulating B cells, and no plasma cells.

Question 17

What is the pattern of inheritance of Leukocyte Adhesion Deficiency 1?

Answer 17

Autosomal Recessive

Question 18

What is the inheritance pattern of Chronic Granulomatous Disease? How can you diagnosis the immunodeficiency?

Answer 18

Autosomal Recessive or X-Linked Inheritance. Diagnosis my measurement of superoxide production

Question 19

What is the inheritance pattern and age of onset of Hyper IgM Syndrome?

Answer 19

X-Linked Recessive diagnosed within the first year of life

Question 20

What is the clinical presentation of Wiskott-Aldrich Syndrome?

Answer 20

Thrombocytopenia, eczema, recurrent pyogenic infections

Question 21

What is the only T cell immunodeficiency with an autosomal dominant inheritance pattern? When is onset?

Answer 21

Job Syndrome - onset during childhood

Question 22

What is the difference between Bare Lymphocyte Syndromes 1 & 2?

Answer 22

Bare Lymphocyte Syndrome 1 = Mutation in TAP protein causes decreased MHC I levels and thus lower CD8 T cell count

Bare Lymphocyte Syndrome 2 = Failure to express MHC II that results in low CD4 T cell numbers and antibodies

Question 23

Individuals a T cell immunodeficiency are more susceptible to what types of infections?

Answer 23

Intracellular bacteria, viruses - lack of CD8+ T cells responsible for killing infected cells

Question 24

True/False. The 10 warning signs of primary immunodeficiency are the same for adults and children.

Answer 24

False. While the warning signs are the same, the number of requirements may change. In general, children require more repeated infections than adults to raise concerns of a primary immunodeficiency.

Question 25

A newborn presents to the clinic with recurrent skin infections, absent pus, and poor wound healing. What immunodeficiency is this child likely suffering from? What is the mechanism of the immunodeficiency?

Answer 25

Leukocyte Adhesion Deficiency 1 - Mutation in CD18 that inhibits phagocyte migration and chemotaxis

Question 26

A patient is said to be missing B & T cells. What immunodeficiency do they have? What is the cause of the immunodeficiency?

Answer 26

RAG Deficiency SCID - caused by a mutation in RAG genes which are needed for VDJ recombination during BRC & TCR generation

Question 27

A patient is known to have a T cell immunodeficiency, but cannot remember which one. They tell you they have frequent viral infections. What is the likely immunodeficiency?

Answer 27

Bare Lymphocyte Syndrome 1

Question 28

What immunodeficiency presents with high IgM levels and low levels of all other antibodies? What is the clinical presentation?

Answer 28

Hyper IgM Syndrome - due to deficiency of CD40L on T cells, recurrent pyogenic infections, increased risk of opportunistic infections, neutropenia, liver disease

Question 29

What immunodeficiency is caused by a mutation in the WASp gene? What are the immunological implications?

Answer 29

Wiskott-Aldrich Syndrome inhibits cell signaling (signal transduction) and adhesion and causes low IgM, IgG, and platelets and increased IgA & IgE. Clinically, thrombocytopenia, pyogenic infections, and eczema

Question 30

What immunodeficiency has sporadic inheritance and presents during teens or early 20s?

Answer 30

Common Variable Immunodeficiency

Question 31

How does a primary immunodeficiency differ from a secondary immunodeficiency?

Answer 31

A primary immunodeficiency is due to a genetic defect and frequently manifests in childhood. A secondary immunodeficiency is not genetic and is the result of malnutrition, cancer, or immunosuppressant drugs.

Question 32

What are the immunological defects in Chediak-Higashi syndrome? How do these defects present clinically?

Answer 32

Defect due to nonsense mutation in LYST in phagolysosome fusion, granule structural defects, and presence of giant lysosomes. Clinically, patients present with recurrent staph and strep infections, partial albinism, and neuropathy. Diagnose from large granules in white blood cells, neutrophils, and monocytes; PAN

Question 33

A parent brings their newborn to the clinic and is worried they may have DiGeorge Syndrome. How can you diagnose this immunodeficiency?

Answer 33

Absence of thymic shadow on imaging

Question 34

How might you expect a patient with X-linked aggamaglobulinemia to present at clinic?

Answer 34

Recurrent bacterial infections of the respiratory tract with likely undetectable IgA and IgM levels

Question 35

B cell immunodeficiencies increase susceptibility to what types of infections?

Answer 35

Extracellular bacteria - lack antibodies for opsonization