Immunology

Question 1

A 3-month-old male infant presents with recurrent pneumonia, chronic diarrhea, and oral thrush. He has lymphopenia and absent thymic shadow on chest X-ray. What is the most likely diagnosis?
a) DiGeorge syndrome
b) X-linked agammaglobulinemia
c) Severe combined immunodeficiency (SCID)
d) Chronic granulomatous disease

Answer 1

Correct Answer: c

Severe Combined Immunodeficiency (SCID) is a life-threatening primary immunodeficiency that presents in infancy with recurrent infections, chronic diarrhea, oral thrush, and failure to thrive. Absent thymic shadow, lymphopenia, and severe T-cell deficiency are classic findings. DiGeorge syndrome may also show thymic hypoplasia but includes hypocalcemia and cardiac defects. X-linked agammaglobulinemia shows low B cells and Ig levels, but normal T cell count. CGD presents with recurrent catalase-positive infections, not lymphopenia.

Question 2

A 6-month-old boy presents with recurrent otitis media and pneumonia. Lab results show very low levels of all immunoglobulin classes and absent B cells. Which gene is most likely mutated?
a) CD40 ligand
b) BTK (Bruton’s tyrosine kinase)
c) RAG1
d) CYBB

Answer 2

Correct Answer: b

X-linked agammaglobulinemia (Bruton’s disease) is caused by a mutation in the BTK gene, leading to a block in B-cell development. This results in absent B cells and very low levels of all immunoglobulin isotypes. It typically presents after 6 months of age when maternal IgG wanes. CD40L mutations cause Hyper-IgM syndrome. RAG1 mutations affect V(D)J recombination, leading to SCID. CYBB mutations cause CGD.

Question 3

A child presents with recurrent sinopulmonary infections and has elevated serum IgM with low IgG and IgA. Which of the following is the most likely diagnosis?
a) Common variable immunodeficiency
b) Hyper-IgM syndrome
c) Selective IgA deficiency
d) Wiskott-Aldrich syndrome

Answer 3

Correct Answer: b

Hyper-IgM syndrome is caused by a defect in class-switch recombination, often due to CD40 ligand (CD40L) deficiency on T cells. This leads to normal or elevated IgM with markedly low IgG, IgA, and IgE, resulting in recurrent sinopulmonary and opportunistic infections. CVID shows low IgG and either IgA or IgM but usually in older children. Selective IgA deficiency presents with low IgA only. Wiskott-Aldrich has eczema, thrombocytopenia, and recurrent infections.

Question 4

A 5-year-old boy has a history of recurrent skin abscesses and pneumonia with catalase-positive organisms. The Nitroblue Tetrazolium (NBT) test is abnormal. What is the most likely diagnosis?
a) Leukocyte adhesion deficiency
b) Chronic granulomatous disease
c) Severe combined immunodeficiency
d) Hyper-IgE syndrome

Answer 4

Correct Answer: b

Chronic Granulomatous Disease (CGD) results from a defect in the NADPH oxidase complex, leading to impaired production of reactive oxygen species. Children present with recurrent infections by catalase-positive organisms (e.g., Staph aureus, Serratia, Nocardia, Aspergillus). The NBT test is abnormal (fails to turn blue) due to defective neutrophil oxidative burst. LAD presents with delayed cord separation and poor wound healing. SCID presents in infancy with lymphopenia. Hyper-IgE syndrome involves eczema and coarse facies.

Question 5

A male infant has persistent diarrhea, failure to thrive, and severe eczema. Labs show thrombocytopenia with small platelets, elevated IgE and IgA, and low IgM. What is the most likely diagnosis?
a) Severe combined immunodeficiency
b) Hyper-IgM syndrome
c) Wiskott-Aldrich syndrome
d) Ataxia-telangiectasia

Answer 5

Correct Answer: c

Wiskott-Aldrich syndrome is an X-linked recessive disorder caused by a mutation in the WASP gene. It presents with the triad of eczema, recurrent infections, and thrombocytopenia with small platelets. Immunoglobulin profile shows low IgM and elevated IgA and IgE. SCID presents earlier with lymphopenia. Hyper-IgM syndrome has high IgM. Ataxia-telangiectasia features ataxia and telangiectasias, not eczema or thrombocytopenia.

Question 6

A 4-year-old child presents with recurrent respiratory tract infections. He has normal B and T cell counts but markedly reduced serum IgG and IgA. What is the most likely diagnosis?
a) Selective IgA deficiency
b) Hyper-IgM syndrome
c) Common variable immunodeficiency (CVID)
d) X-linked agammaglobulinemia

Answer 6

Correct Answer: c

Common Variable Immunodeficiency (CVID) presents in older children or adults with recurrent infections, particularly of the respiratory tract. It is characterized by low IgG and low IgA and/or IgM, despite normal numbers of B and T cells. Selective IgA deficiency involves only low IgA. Hyper-IgM syndrome has high or normal IgM with low other Ig classes. X-linked agammaglobulinemia has absent B cells and all immunoglobulins.

Question 7

A 6-year-old boy has a history of ataxia, recurrent sinopulmonary infections, and visible dilated conjunctival blood vessels. Which laboratory finding is most likely?
a) Elevated IgM
b) Decreased serum alpha-fetoprotein (AFP)
c) Decreased serum IgA
d) Increased neutrophil oxidative burst

Answer 7

Correct Answer: c

Ataxia-telangiectasia is a primary immunodeficiency caused by mutations in the ATM gene. It presents with a triad of progressive cerebellar ataxia, oculocutaneous telangiectasias, and immunodeficiency (especially low IgA). AFP is typically elevated, not decreased. Elevated IgM is more typical of Hyper-IgM syndrome. Neutrophil oxidative burst is impaired in CGD, not A-T.

Question 8

A 10-month-old infant presents with recurrent Candida infections of the mouth and skin. Which immune defect is most likely responsible?
a) T-cell dysfunction
b) B-cell dysfunction
c) Neutrophil dysfunction
d) Complement deficiency

Answer 8

Correct Answer: a

Chronic mucocutaneous candidiasis is typically due to T-cell dysfunction, particularly affecting the Th17 pathway, which impairs mucosal immunity against fungal pathogens like Candida. B-cell dysfunction results in bacterial infections. Neutrophil dysfunction (e.g., CGD) leads to catalase-positive bacterial/fungal infections. Complement deficiencies predispose to encapsulated bacterial infections and Neisseria infections.

Question 9

A 7-year-old boy presents with recurrent meningococcal infections. Which of the following immunologic investigations is most appropriate to perform first?
a) Nitroblue tetrazolium test
b) Serum immunoglobulin levels
c) CH50 complement assay
d) Dihydrorhodamine (DHR) test

Answer 9

Correct Answer: c

Recurrent Neisseria (meningococcal) infections strongly suggest a terminal complement deficiency (C5–C9), which impairs formation of the membrane attack complex (MAC). The CH50 assay is a functional screen of the classical complement pathway, useful to detect such deficiencies. NBT and DHR are used for diagnosing CGD. Serum Ig levels assess antibody-mediated immunity.

Question 10

A newborn has delayed separation of the umbilical cord, omphalitis, and persistent leukocytosis. Which of the following is the most likely underlying defect?
a) NADPH oxidase deficiency
b) CD18 integrin deficiency
c) CD40L mutation
d) BTK gene mutation

Answer 10

Correct Answer: b

Leukocyte Adhesion Deficiency (LAD) is caused by a CD18 integrin deficiency, which impairs leukocyte migration and adhesion. It presents with delayed cord separation (>30 days), recurrent bacterial infections without pus, and marked leukocytosis. NADPH oxidase deficiency causes CGD. CD40L mutation causes Hyper-IgM syndrome. BTK mutation causes X-linked agammaglobulinemia.

Question 11

Which of the following laboratory findings is most consistent with Selective IgA deficiency?
a) Low IgG, low IgA, low IgM
b) Normal IgG, low IgA, normal IgM
c) Low IgG, low IgM, normal IgA
d) Low IgG, normal IgA, low IgE

Answer 11

Correct Answer: b

Selective IgA deficiency is the most common primary immunodeficiency. It is characterized by isolated low serum IgA with normal IgG and IgM levels. Most patients are asymptomatic, but some may present with recurrent mucosal infections, allergies, or autoimmune disorders. Other immunoglobulin levels are typically unaffected.

Question 12

A 9-month-old infant presents with recurrent pneumonia and chronic diarrhea. Flow cytometry shows absence of both CD3+ and CD19+ cells. What is the most likely diagnosis?
a) X-linked agammaglobulinemia
b) DiGeorge syndrome
c) SCID (T-B- type)
d) Hyper-IgM syndrome

Answer 12

Correct Answer: c

Severe Combined Immunodeficiency (SCID) of the T−B− type shows absence of both T cells (CD3+) and B cells (CD19+). It presents early in life with severe infections, failure to thrive, diarrhea, and lymphopenia. X-linked agammaglobulinemia has absent B cells but normal T cells. DiGeorge syndrome has low T cells but normal B cells. Hyper-IgM syndrome has normal B cell numbers and abnormal class switching.

Question 13

A child has recurrent infections and is found to have a normal neutrophil count but defective intracellular killing. Which of the following tests is most appropriate to confirm the diagnosis?
a) CH50 assay
b) Nitroblue tetrazolium (NBT) test
c) Flow cytometry for CD3 and CD19
d) Serum immunoglobulin levels

Answer 13

Correct Answer: b

Chronic Granulomatous Disease (CGD) presents with recurrent infections due to impaired intracellular killing by neutrophils, despite a normal neutrophil count. The Nitroblue Tetrazolium (NBT) test is used to assess the oxidative burst function of neutrophils. An abnormal test (no color change) indicates CGD. CH50 assesses complement. Flow cytometry for CD markers is used for lymphocyte evaluation. Serum immunoglobulins are normal in CGD.

Question 14

Which of the following is a hallmark of C1 esterase inhibitor deficiency?
a) Urticaria with pruritus
b) Angioedema without urticaria
c) Petechiae and purpura
d) Bronchospasm with wheezing

Answer 14

Correct Answer: b

C1 esterase inhibitor deficiency causes Hereditary Angioedema (HAE), which presents with recurrent episodes of angioedema without urticaria or pruritus. It is due to uncontrolled bradykinin production leading to vascular leakage. The absence of urticaria distinguishes it from allergic angioedema. Petechiae and purpura suggest a bleeding disorder, and bronchospasm is characteristic of asthma or anaphylaxis.

Question 15

A 2-year-old child with recurrent pneumonia is found to have normal levels of all immunoglobulins. Flow cytometry shows absent class-switched memory B cells. What is the most likely diagnosis?
a) Selective IgA deficiency
b) X-linked agammaglobulinemia
c) Hyper-IgM syndrome
d) Common variable immunodeficiency

Answer 15

Correct Answer: c

Hyper-IgM syndrome is caused by a defect in class switch recombination, typically due to CD40L mutation on T cells. It results in inability of B cells to undergo isotype switching, leading to absent class-switched memory B cells, despite normal or elevated IgM. IgA deficiency does not affect class switching globally. X-linked agammaglobulinemia shows absent B cells. CVID presents later with low IgG and impaired antibody responses.

Question 16

A 6-year-old girl presents with a history of autoimmune hemolytic anemia, immune thrombocytopenia, and lymphadenopathy. Immunoglobulin levels show low IgG, low IgA, and normal IgM. What is the most likely diagnosis?
a) Hyper-IgM syndrome
b) Common variable immunodeficiency (CVID)
c) Selective IgA deficiency
d) Autoimmune lymphoproliferative syndrome (ALPS)

Answer 16

Correct Answer: b

Common Variable Immunodeficiency (CVID) can present with autoimmune complications (such as autoimmune cytopenias), lymphadenopathy, and low levels of IgG and IgA, often with normal or low IgM. It has a variable onset and may be associated with recurrent infections. Hyper-IgM typically has high IgM. Selective IgA deficiency does not cause autoimmune cytopenias. ALPS presents with autoimmune cytopenias and lymphoproliferation but without significant hypogammaglobulinemia.

Question 17

A 3-year-old child presents with severe eczema, food allergies, and recurrent skin infections. Peripheral smear shows eosinophilia, and IgE levels are markedly elevated. What is the most likely diagnosis?
a) Hyper-IgM syndrome
b) Job syndrome (Hyper-IgE syndrome)
c) Wiskott-Aldrich syndrome
d) Atopic dermatitis

Answer 17

Correct Answer: b

Job syndrome (Hyper-IgE syndrome) is characterized by eczema, recurrent staphylococcal skin infections, eosinophilia, and very high IgE levels. It is often due to a STAT3 mutation leading to defective neutrophil chemotaxis. Hyper-IgM has high IgM, not IgE. Wiskott-Aldrich includes thrombocytopenia and immune deficiency. Atopic dermatitis alone doesn’t cause severe infections or extreme IgE elevation.

Question 18

A child presents with persistent lymphadenopathy, hepatosplenomegaly, and autoimmune cytopenias. Laboratory tests show elevated double-negative T cells (CD3+ CD4− CD8−). What is the most likely diagnosis?
a) Wiskott-Aldrich syndrome
b) Severe combined immunodeficiency
c) Autoimmune lymphoproliferative syndrome (ALPS)
d) Common variable immunodeficiency

Answer 18

Correct Answer: c

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by non-malignant lymphadenopathy, hepatosplenomegaly, and autoimmune cytopenias. A key diagnostic marker is the presence of elevated double-negative T cells (CD3+ CD4− CD8−). It results from mutations in the Fas pathway leading to defective apoptosis of lymphocytes. Wiskott-Aldrich presents with thrombocytopenia. SCID manifests early with infections and lymphopenia. CVID presents later and lacks elevated double-negative T cells.

Question 19

Which of the following vaccines is contraindicated in a child with severe combined immunodeficiency (SCID)?
a) Inactivated influenza vaccine
b) Pneumococcal conjugate vaccine
c) Oral rotavirus vaccine
d) Hepatitis B vaccine

Answer 19

Correct Answer: c

Oral rotavirus vaccine is a live attenuated vaccine, and live vaccines are contraindicated in patients with SCID due to the risk of uncontrolled infection. Inactivated influenza, pneumococcal, and hepatitis B vaccines are safe and recommended for immunodeficient patients, including those with SCID, under specialist guidance.

Question 20

A newborn presents with hypocalcemia, cleft palate, and congenital heart defects. Flow cytometry shows low CD3+ T cells. What is the most likely diagnosis?
a) SCID
b) DiGeorge syndrome
c) Wiskott-Aldrich syndrome
d) Ataxia-telangiectasia

Answer 20

Correct Answer: b

DiGeorge syndrome is caused by a 22q11.2 deletion, resulting in failure of 3rd and 4th pharyngeal pouch development. Clinical features include hypocalcemia (due to hypoplasia of parathyroid glands), congenital heart defects, cleft palate, and T-cell deficiency (low CD3+ T cells) due to thymic hypoplasia. SCID presents with severe infections early in life. Wiskott-Aldrich includes thrombocytopenia and eczema. Ataxia-telangiectasia has cerebellar ataxia and telangiectasia, not hypocalcemia.

Question 21

Which of the following findings best differentiates Wiskott-Aldrich Syndrome (WAS) from other primary immunodeficiencies?
a) Severe T-cell lymphopenia
b) Recurrent bacterial infections
c) Thrombocytopenia with small platelets
d) Elevated IgE and eosinophilia

Answer 21

Correct Answer: c

Wiskott-Aldrich Syndrome (WAS) is an X-linked disorder caused by mutations in the WAS gene. It presents with a classic triad: eczema, recurrent infections, and thrombocytopenia with small-sized platelets. This platelet abnormality is a distinguishing feature not seen in other immunodeficiencies. T-cell lymphopenia and recurrent infections are common in many immunodeficiencies. Elevated IgE and eosinophilia are more typical of Job syndrome.

Question 22

A 5-year-old child presents with progressive cerebellar ataxia and ocular telangiectasias. Immunological testing reveals low IgA levels. What is the most likely diagnosis?
a) Wiskott-Aldrich syndrome
b) Ataxia-telangiectasia
c) DiGeorge syndrome
d) Hyper-IgM syndrome

Answer 22

Correct Answer: b

Ataxia-telangiectasia (AT) is a rare autosomal recessive disorder caused by mutations in the ATM gene. It presents with progressive cerebellar ataxia, ocular telangiectasias, and immunodeficiency, particularly low IgA. It is also associated with increased risk of malignancy. Wiskott-Aldrich includes thrombocytopenia and eczema. DiGeorge syndrome includes hypocalcemia and cardiac defects. Hyper-IgM has elevated or normal IgM with low other immunoglobulins.

Question 23

A 3-year-old child presents with recurrent infections, eczema, and bleeding tendencies. Labs show thrombocytopenia with small platelets and elevated IgE. What is the most likely diagnosis?
a) Job syndrome
b) Wiskott-Aldrich syndrome
c) SCID
d) Hyper-IgM syndrome

Answer 23

Correct Answer: b

Wiskott-Aldrich syndrome (WAS) presents with a triad: eczema, recurrent infections, and thrombocytopenia with small platelets. It is caused by a mutation in the WAS gene. IgE may be elevated. Job syndrome has eczema and high IgE but no bleeding tendency. SCID involves profound immunodeficiency without thrombocytopenia. Hyper-IgM presents with normal platelet counts and recurrent infections.

Question 24

Which of the following pathogens poses the highest risk in a child with chronic granulomatous disease (CGD)?
a) Streptococcus pneumoniae
b) Escherichia coli
c) Staphylococcus aureus
d) Haemophilus influenzae

Answer 24

Correct Answer: c

Chronic Granulomatous Disease (CGD) is a phagocyte disorder caused by defective NADPH oxidase, impairing oxidative burst. Patients are especially susceptible to catalase-positive organisms, such as Staphylococcus aureus, Serratia marcescens, Burkholderia cepacia, Nocardia, and Aspergillus. Streptococcus pneumoniae and Haemophilus influenzae are encapsulated but not catalase-positive, and less associated with CGD.

Question 25

Which primary immunodeficiency is most commonly associated with anaphylactic reactions to blood transfusions? a) Severe combined immunodeficiency (SCID) b) Selective IgA deficiency c) Wiskott-Aldrich syndrome d) Chronic granulomatous disease (CGD)

Answer 25

Correct Answer: b **Selective IgA deficiency** is the most common primary immunodeficiency. These patients may develop **anti-IgA antibodies**, which can lead to **anaphylactic reactions during blood transfusions containing IgA**. Such reactions are due to immune response against transfused IgA proteins. SCID, WAS, and CGD do not typically show this reaction pattern with transfusions.

Question 26

A neonate presents with severe infections, chronic diarrhea, and failure to thrive. Lymphocyte count is profoundly low, and chest X-ray shows absent thymic shadow. What is the most likely diagnosis? a) DiGeorge syndrome b) Wiskott-Aldrich syndrome c) SCID (Severe Combined Immunodeficiency) d) Ataxia-telangiectasia

Answer 26

Correct Answer: c **Severe Combined Immunodeficiency (SCID)** presents early in infancy with **severe infections**, **chronic diarrhea**, **failure to thrive**, and **lymphopenia**. **Absent thymic shadow on chest X-ray** suggests profound T-cell deficiency. DiGeorge may also show absent thymus, but usually with hypocalcemia and cardiac defects. Wiskott-Aldrich has thrombocytopenia. Ataxia-telangiectasia presents later with ataxia and telangiectasias.

Question 27

Which of the following immunodeficiencies is most associated with susceptibility to Neisseria infections? a) Chronic granulomatous disease b) Complement deficiency (late components C5–C9) c) Severe combined immunodeficiency d) Hyper-IgE syndrome

Answer 27

Correct Answer: b **Deficiency of the terminal complement components (C5–C9)** leads to impaired **membrane attack complex (MAC)** formation, which is essential for lysis of **Neisseria species**. As a result, these patients are highly susceptible to **recurrent meningococcal infections**. CGD involves phagocyte dysfunction but not increased Neisseria risk. SCID causes broad susceptibility. Hyper-IgE syndrome is linked to bacterial and fungal skin infections.

Question 28

A 1-year-old male presents with recurrent pneumonia and otitis media. Lab tests show absent B cells and low immunoglobulin levels. Which gene is most likely mutated? a) RAG1 b) CD40L c) BTK (Bruton's tyrosine kinase) d) AIRE

Answer 28

Correct Answer: c **X-linked agammaglobulinemia (XLA)** is caused by a mutation in the **BTK gene**, leading to a block in B cell development. It results in **absent or very low B cells**, and **markedly reduced immunoglobulin levels**, causing recurrent bacterial infections. RAG1 is associated with SCID. CD40L mutation leads to Hyper-IgM syndrome. AIRE mutations cause autoimmune polyendocrinopathy (APECED).

Question 29

A child with known selective IgA deficiency presents with anaphylaxis during a blood transfusion. What is the best immediate management step? a) Start intravenous fluids and observe b) Administer epinephrine intramuscularly c) Give antihistamines and corticosteroids only d) Transfuse with washed red blood cells

Answer 29

Correct Answer: b **Anaphylaxis** is a medical emergency and the first-line treatment is **intramuscular epinephrine**. In patients with **IgA deficiency**, exposure to IgA in blood products can lead to anaphylactic reactions due to anti-IgA antibodies. **Washed red cells** may be used in future transfusions, but the **immediate** step is epinephrine. Fluids and antihistamines are supportive, not primary.

Question 30

Which laboratory test is most useful in screening for chronic granulomatous disease (CGD)? a) Nitroblue tetrazolium (NBT) test b) Serum IgA level c) ANA (Antinuclear antibody) d) CD4/CD8 ratio

Answer 30

Correct Answer: a **Chronic Granulomatous Disease (CGD)** is a defect in the **oxidative burst of phagocytes**, particularly involving the NADPH oxidase complex. The **nitroblue tetrazolium (NBT) test** assesses this function and is used to screen for CGD. A failed NBT reduction indicates CGD. Serum IgA is used in IgA deficiency. ANA is for autoimmune diseases. CD4/CD8 ratio is more relevant in T cell immunodeficiencies like HIV.

Question 31

A 4-year-old child presents with recurrent sinopulmonary infections. Serum studies reveal normal IgG, IgA, and IgM, but an absent response to pneumococcal vaccination. What is the likely diagnosis? a) Severe combined immunodeficiency (SCID) b) Hyper-IgM syndrome c) Specific antibody deficiency d) Common variable immunodeficiency (CVID)

Answer 31

Correct Answer: c **Specific antibody deficiency** is characterized by **normal immunoglobulin levels**, but the child **fails to mount protective antibody responses** to polysaccharide antigens (e.g., pneumococcal vaccines). It is a functional B-cell defect. SCID would show profound lymphopenia. Hyper-IgM has low IgG/IgA. CVID typically presents with low IgG and poor antibody responses.

Question 32

A child with recurrent infections is found to have a mutation in CD40 ligand. Which immunoglobulin is typically elevated in this condition? a) IgA b) IgE c) IgG d) IgM

Answer 32

Correct Answer: d **Hyper-IgM syndrome** is caused by a defect in **CD40 ligand (CD40L)** on T cells, which impairs class-switch recombination in B cells. As a result, patients have **high or normal levels of IgM**, but **low IgG, IgA, and IgE**. This leads to recurrent infections and opportunistic pathogens. The elevated IgM is a diagnostic clue.

Question 33

Which of the following laboratory findings is most consistent with common variable immunodeficiency (CVID)? a) Decreased IgG, IgA, and IgM with normal B cell numbers b) Absent B cells and all immunoglobulin classes c) Elevated IgM with low IgA and IgG d) Isolated low IgA with normal IgG and IgM

Answer 33

Correct Answer: a **Common variable immunodeficiency (CVID)** is characterized by **low levels of IgG and at least one other immunoglobulin (IgA or IgM)**, with **normal or low B cell numbers**. The condition typically presents in adolescence or adulthood with recurrent bacterial infections and autoimmune disease. Option b describes X-linked agammaglobulinemia. Option c fits hyper-IgM syndrome. Option d describes selective IgA deficiency.

Question 34

Which of the following best describes the inheritance pattern of Severe Combined Immunodeficiency (SCID) due to IL2RG gene mutation? a) Autosomal dominant b) Autosomal recessive c) X-linked recessive d) Mitochondrial

Answer 34

Correct Answer: c **SCID** due to **IL2RG gene mutation** is inherited in an **X-linked recessive** pattern. This form is also known as **X-linked SCID**, and it primarily affects males. It leads to absent T and NK cells with non-functional B cells. Autosomal recessive SCID can occur with other gene mutations like ADA or JAK3.

Question 35

Which of the following primary immunodeficiencies is most commonly associated with autoimmune diseases such as type 1 diabetes and hypothyroidism? a) Severe Combined Immunodeficiency (SCID) b) Common Variable Immunodeficiency (CVID) c) Chronic Granulomatous Disease (CGD) d) Hyper-IgE Syndrome

Answer 35

Correct Answer: b **Common Variable Immunodeficiency (CVID)** is associated not only with recurrent bacterial infections but also with a high incidence of **autoimmune diseases**, including **autoimmune thyroiditis**, **type 1 diabetes**, **cytopenias**, and **gastrointestinal disorders**. SCID presents early and severely without autoimmune features. CGD is linked to infections and granuloma formation, not autoimmunity. Hyper-IgE presents with infections and eczema.

Question 36

Which of the following is the most appropriate confirmatory test for DiGeorge syndrome? a) Flow cytometry for CD19 b) Serum immunoglobulin levels c) FISH for 22q11.2 deletion d) NBT test

Answer 36

Correct Answer: c **DiGeorge syndrome** (22q11.2 deletion syndrome) is confirmed using **FISH (Fluorescence In Situ Hybridization)** to detect the microdeletion on chromosome 22. It presents with **thymic hypoplasia**, **hypocalcemia**, **cardiac defects**, and sometimes **facial dysmorphisms**. Flow cytometry for CD19 detects B cells (not specific). Immunoglobulin levels may be normal. NBT is used for CGD.

Question 37

Which of the following is a hallmark feature of Ataxia-Telangiectasia? a) Elevated IgA b) Defective neutrophil oxidative burst c) Cerebellar ataxia and oculocutaneous telangiectasias d) Microthrombocytopenia

Answer 37

Correct Answer: c **Ataxia-Telangiectasia (A-T)** is an autosomal recessive disorder caused by mutations in the **ATM gene**. It is characterized by **progressive cerebellar ataxia**, **oculocutaneous telangiectasias**, **immunodeficiency** (especially IgA deficiency), and increased risk of malignancy. Elevated IgA is incorrect (IgA is usually low). Oxidative burst defect is seen in CGD. Microthrombocytopenia is seen in Wiskott-Aldrich syndrome.

Question 38

Which immunodeficiency is associated with albinism, recurrent infections, and giant cytoplasmic granules in neutrophils? a) Chediak-Higashi syndrome b) Hyper-IgE syndrome c) Wiskott-Aldrich syndrome d) Chronic granulomatous disease

Answer 38

Correct Answer: a **Chediak-Higashi syndrome** is a rare autosomal recessive disorder characterized by **partial oculocutaneous albinism**, **recurrent pyogenic infections**, and **giant lysosomal granules** in neutrophils. It is caused by a defect in the **LYST gene**, affecting lysosomal trafficking. Hyper-IgE syndrome shows eczema and high IgE. Wiskott-Aldrich shows eczema, immunodeficiency, and thrombocytopenia. CGD affects oxidative burst.

Question 39

A male infant has persistent eczema, thrombocytopenia with small platelets, and recurrent infections. What is the most likely diagnosis? a) Ataxia-telangiectasia b) Hyper-IgE syndrome c) Wiskott-Aldrich syndrome d) Severe combined immunodeficiency (SCID)

Answer 39

Correct Answer: c **Wiskott-Aldrich syndrome (WAS)** is an X-linked recessive disorder characterized by the triad of **eczema**, **thrombocytopenia with small platelets**, and **recurrent infections** due to combined immunodeficiency. It results from mutations in the **WASP gene**. Ataxia-telangiectasia features cerebellar ataxia. Hyper-IgE syndrome has high IgE and boils. SCID presents earlier and more severely.

Question 40

Which of the following features is most characteristic of Hyper-IgE Syndrome (Job Syndrome)? a) Severe neutropenia b) High serum IgA and low IgM c) Cold abscesses and retained primary teeth d) Profound lymphopenia at birth

Answer 40

Correct Answer: c **Hyper-IgE Syndrome (Job Syndrome)** is characterized by **cold (non-inflamed) staphylococcal abscesses**, **recurrent pneumonia**, **eczema**, **retained primary teeth**, and **very high serum IgE** levels. It is often caused by mutations in the **STAT3 gene**. Neutropenia is more characteristic of severe congenital neutropenia. Lymphopenia is typical in SCID. IgA/IgM abnormalities suggest other B-cell disorders.

Question 41

Which primary immunodeficiency is classically associated with failure of the umbilical cord to fall off within the first month of life? a) Leukocyte adhesion deficiency (LAD) b) Severe combined immunodeficiency (SCID) c) DiGeorge syndrome d) Wiskott-Aldrich syndrome

Answer 41

Correct Answer: a **Leukocyte adhesion deficiency (LAD)** is a rare immunodeficiency caused by defective adhesion molecules on neutrophils, particularly **CD18 (LFA-1)**. It leads to **impaired migration of neutrophils** to sites of infection. A hallmark sign is **delayed separation of the umbilical cord** beyond 30 days and absence of pus formation despite severe infections. SCID and DiGeorge present differently, and Wiskott-Aldrich does not affect neutrophil function.

Question 42

Which of the following vaccines is contraindicated in a child with severe T-cell immunodeficiency? a) Inactivated polio vaccine (IPV) b) Pneumococcal conjugate vaccine (PCV) c) MMR (measles, mumps, rubella) d) Hepatitis B vaccine

Answer 42

Correct Answer: c **Live attenuated vaccines** like **MMR** are **contraindicated** in children with **severe T-cell immunodeficiency** (e.g., SCID) because they can lead to disseminated infections. **IPV, PCV, and Hepatitis B** vaccines are inactivated or subunit vaccines and are considered safe in these patients.

Question 43

Which of the following findings is most consistent with X-linked agammaglobulinemia (Bruton’s disease)? a) Decreased T cells, normal B cells, low immunoglobulins b) Absent B cells, very low immunoglobulins, normal T cells c) Normal B and T cells, elevated IgE and eosinophils d) Increased B cells, increased immunoglobulins

Answer 43

Correct Answer: b **X-linked agammaglobulinemia (Bruton’s disease)** is characterized by **absent or very low B cells** and **severely reduced levels of all immunoglobulin classes**. T cell counts are normal. It results from mutations in the **BTK gene**, which is crucial for B-cell development. This leads to recurrent bacterial infections after maternal antibodies wane (after 6 months of age).

Question 44

Which of the following primary immunodeficiencies is most commonly associated with increased susceptibility to Neisseria infections? a) Complement C5-C9 deficiency b) Hyper-IgM syndrome c) DiGeorge syndrome d) Severe combined immunodeficiency (SCID)

Answer 44

Correct Answer: a **Terminal complement deficiencies (C5 to C9)** impair the formation of the **membrane attack complex (MAC)**, which is crucial for killing Neisseria species. This leads to **recurrent and severe Neisseria meningitidis or gonorrhoeae infections**. Other immunodeficiencies like Hyper-IgM, SCID, or DiGeorge are not specifically linked to Neisseria.

Question 45

Which of the following is the most likely finding in a newborn with SCID due to adenosine deaminase (ADA) deficiency? a) Elevated lymphocyte count with poor vaccine response b) Severe lymphopenia, especially of T, B, and NK cells c) Thrombocytopenia with small platelets d) Normal immune function with selective IgA deficiency

Answer 45

Correct Answer: b **ADA-SCID** is a form of **autosomal recessive Severe Combined Immunodeficiency** due to a defect in **adenosine deaminase**, which is toxic to lymphocytes. It leads to profound **lymphopenia**, with absent or severely reduced **T, B, and NK cells**, resulting in **severe opportunistic infections** and failure to thrive. It is one of the most severe forms of SCID and presents in infancy. Thrombocytopenia is typical in Wiskott-Aldrich. IgA deficiency is not associated with severe infections in infancy.

Question 46

Which of the following cytokines is critical for class switch recombination in B cells and is deficient in Hyper-IgM Syndrome due to CD40L mutation? a) IL-2 b) IL-4 c) IFN-gamma d) TNF-alpha

Answer 46

Correct Answer: b **IL-4** is one of the key cytokines that promotes **class switch recombination** in B cells, particularly toward IgE and IgG production. In **Hyper-IgM Syndrome** caused by **CD40 ligand (CD40L) mutation**, interaction between T helper cells and B cells is impaired, preventing effective class switching. As a result, **IgM is elevated**, while **IgG, IgA, and IgE** are reduced. IL-2 is involved in T cell proliferation, IFN-gamma in macrophage activation, and TNF-alpha in inflammation.

Question 47

Which test is most useful for assessing neutrophil oxidative burst activity in suspected Chronic Granulomatous Disease (CGD)? a) Flow cytometry for CD40L expression b) Nitroblue tetrazolium (NBT) test c) FISH for 22q11.2 deletion d) Serum IgA levels

Answer 47

Correct Answer: b **Chronic Granulomatous Disease (CGD)** is characterized by defective NADPH oxidase, leading to impaired **oxidative burst** in neutrophils. The **Nitroblue Tetrazolium (NBT) test** is a classic screening test that shows failure of neutrophils to reduce NBT dye. **Dihydrorhodamine (DHR) flow cytometry** is a more modern and sensitive test. CD40L, FISH, and serum IgA are not used for CGD diagnosis.

Question 48

A child presents with recurrent Neisseria infections but otherwise normal immune function. Which screening test is most appropriate? a) Total IgG and IgA levels b) Nitroblue tetrazolium test c) Total hemolytic complement assay (CH50) d) Flow cytometry for T cell subsets

Answer 48

Correct Answer: c **Recurrent Neisseria infections** suggest a defect in the **terminal complement pathway** (C5-C9). The **CH50 test** assesses the functional activity of the entire classical complement pathway and is a good **screening test for terminal complement deficiencies**. IgG/IgA levels assess humoral immunity. NBT test is for CGD. T cell flow cytometry is not relevant for Neisseria infections specifically.

Question 49

Which of the following is the most characteristic feature of selective IgA deficiency? a) Increased risk of disseminated mycobacterial infection b) High serum IgA and eosinophilia c) Recurrent respiratory and gastrointestinal infections with normal IgG and IgM d) Severe lymphopenia at birth

Answer 49

Correct Answer: c **Selective IgA deficiency** is the most common primary immunodeficiency. It is characterized by **undetectable serum IgA** with **normal IgG and IgM**, leading to **recurrent respiratory and gastrointestinal infections**. These patients may also develop autoimmune diseases or allergies. Mycobacterial infections are seen in IL-12 or IFN-gamma axis defects. Eosinophilia is not a typical feature. Severe lymphopenia suggests SCID.

Question 50

Which of the following pathogens causes severe disseminated infection in patients with IL-12 receptor deficiency? a) Streptococcus pneumoniae b) Neisseria meningitidis c) Mycobacterium bovis (BCG) d) Candida albicans

Answer 50

Correct Answer: c **IL-12 receptor deficiency** impairs the **Th1 response and IFN-gamma production**, which are critical for defense against **intracellular pathogens**, especially **mycobacteria**. Affected children may develop **severe disseminated BCG infection** after vaccination or infections with non-tuberculous mycobacteria. Streptococcus and Neisseria are extracellular. Candida is a fungal pathogen and not primarily affected by IL-12 pathway defects.