A 7-week-old girl born at term was flagged by newborn screening for undetectable T-cell receptor excision circles (TRECs). She now has oral thrush, diarrhea and poor weight gain. Results: WBC 5.9 x 10^3/µL [5.9 x 10^9/L]; neutrophils 4.8 x 10^3/µL; lymphocytes 0.3 x 10^3/µL. Flow cytometry (cells/µL, with age reference ranges): CD3+ T cells 30 (2,500-5,500); CD19+ B cells 12 (300-2,000); CD16/CD56+ NK cells 8 (170-1,100). IgG 410 mg/dL [4.1 g/L]; IgA and IgM undetectable. A chest film shows no thymic shadow and flared, cupped anterior rib ends. Which defect is most likely?

Common gamma chain (IL2RG) defect

A 2-year-old boy has recurrent sinus and lung infections and now Pneumocystis pneumonia. IgG is 80 mg/dL [0.8 g/L], IgA under 7 mg/dL [0.07 g/L] and IgM 420 mg/dL [4.2 g/L]: IgG and IgA far below, and IgM far above, the age-related ranges. CD19-positive B cells are normal in number. Which defect is most likely?

CD40 ligand on activated T cells

Bruton tyrosine kinase in B-cell precursors

Common gamma chain of cytokine receptors

Universal newborn screening for severe combined immunodeficiency (SCID) in the United States is based on measuring:

T-cell receptor excision circles (TRECs)

CD4 T-cell count by flow cytometry

Immunodeficiency: hereditary and acquired

10 ASCP MLS practice questions on Immunodeficiency: hereditary and acquired, part of Immunology. The first 10 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Hard
A 7-week-old girl born at term was flagged by newborn screening for undetectable T-cell receptor excision circles (TRECs). She now has oral thrush, diarrhea and poor weight gain. Results: WBC 5.9 x 10^3/µL [5.9 x 10^9/L]; neutrophils 4.8 x 10^3/µL; lymphocytes 0.3 x 10^3/µL. Flow cytometry (cells/µL, with age reference ranges): CD3+ T cells 30 (2,500-5,500); CD19+ B cells 12 (300-2,000); CD16/CD56+ NK cells 8 (170-1,100). IgG 410 mg/dL [4.1 g/L]; IgA and IgM undetectable. A chest film shows no thymic shadow and flared, cupped anterior rib ends. Which defect is most likely?
1. A22q11.2 deletion syndrome
2. BRAG1 or RAG2 deficiency
3. CAdenosine deaminase deficiency
4. DCommon gamma chain (IL2RG) defect
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Answer: C · Adenosine deaminase deficiency
The baby lacks T cells, B cells and NK cells (T-B-NK- SCID), while neutrophils are normal. Adenosine deaminase deficiency gives this pattern because deoxyadenosine and dATP build up and are toxic to all developing lymphocytes; the same metabolic defect causes the cupped, flared rib ends. RAG1 or RAG2 defects block T- and B-cell receptor gene rearrangement but spare NK cells (T-B-NK+), and common gamma chain defects are X-linked and give T-B+NK- SCID. In 22q11.2 deletion the thymus is small, but B and NK cells are normal. Her IgG is maternal IgG that crossed the placenta; ADA-SCID is confirmed by low red cell ADA activity and raised dATP.
- A: 22q11.2 deletion lowers T cells but leaves B and NK cells normal.
- B: RAG defects spare NK cells, giving T-B-NK+ SCID.
- D: Common gamma chain SCID is X-linked and keeps B cells (T-B+NK-).
Question 2 · Hard
A 2-year-old boy has recurrent sinus and lung infections and now Pneumocystis pneumonia. IgG is 80 mg/dL [0.8 g/L], IgA under 7 mg/dL [0.07 g/L] and IgM 420 mg/dL [4.2 g/L]: IgG and IgA far below, and IgM far above, the age-related ranges. CD19-positive B cells are normal in number. Which defect is most likely?
1. ACD40 ligand on activated T cells
2. BNADPH oxidase in phagocytes
3. CBruton tyrosine kinase in B-cell precursors
4. DCommon gamma chain of cytokine receptors
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Answer: A · CD40 ligand on activated T cells
This is X-linked hyper-IgM syndrome. CD40 ligand on activated helper T cells binds CD40 on B cells, and that signal is needed for class switching, so B cells keep making IgM while IgG, IgA and IgE stay low. CD40 ligand also activates macrophages, which is why Pneumocystis and Cryptosporidium infections occur. Flow cytometry shows no CD40 ligand on T cells after stimulation.
- B: NADPH oxidase deficiency (CGD) leaves immunoglobulins normal.
- C: BTK deficiency leaves almost no B cells, and IgM is low as well.
- D: Common gamma chain deficiency is SCID, with absent T cells.
Question 3 · Medium
X-linked SCID is caused by mutations in the common gamma chain shared by several interleukin receptors. Which lymphocyte profile is typical?
1. AT- B- NK-
2. BT+ B- NK+
3. CT- B+ NK-
4. DT- B- NK+
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Answer: C · T- B+ NK-
The common gamma chain is part of the receptors for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. Without IL-7 signalling T cells do not develop, and without IL-15 NK cells do not develop. B cells are present in normal or high numbers but work poorly, because they lack T-cell help. JAK3 deficiency gives the same T- B+ NK- pattern, while RAG defects give T- B- NK+ and ADA deficiency T- B- NK-.
- A: Absence of all three fits adenosine deaminase deficiency.
- B: Normal T cells with absent B cells fits X-linked agammaglobulinemia.
- D: T- B- NK+ fits RAG1 or RAG2 deficiency.
Question 4 · Easy
Universal newborn screening for severe combined immunodeficiency (SCID) in the United States is based on measuring:
1. ACD4 T-cell count by flow cytometry
2. BTotal IgG concentration
3. CAdenosine deaminase activity
4. DT-cell receptor excision circles (TRECs)
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Answer: D · T-cell receptor excision circles (TRECs)
TRECs are small circles of DNA cut out when T-cell receptor genes rearrange in the thymus, so they mark newly made naive T cells. They are measured by quantitative PCR on the dried blood spot, and low or absent TRECs are followed up with lymphocyte subset flow cytometry. Every US state now screens for SCID this way. Prematurity and 22q11.2 deletion can also give low TRECs.
- A: Flow cytometry is the confirmatory test, not the screen on a dried blood spot.
- B: A newborn's IgG is mostly from the mother and is normal in SCID.
- C: ADA deficiency is only one cause of SCID, so an ADA assay would miss other forms.
Question 5 · Medium
Under the CDC surveillance staging of HIV infection for people aged 6 years and older, a CD4 count of 350 cells/µL [0.35 x 10^9/L] with no opportunistic illness is:
1. AStage 1
2. BStage 2
3. CStage 3 (AIDS)
4. DStage 0 (early infection)
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Answer: B · Stage 2
For people aged 6 and older, stage 1 is a CD4 count of 500 cells/µL or more, stage 2 is 200 to 499, and stage 3 is below 200 or any stage-3-defining opportunistic illness. The matching percentages are 26% or more, 14% to 25%, and below 14%. Stage 0 is used only when a negative or indeterminate test was documented within 180 days before the first positive. A count of 350 cells/µL with no opportunistic illness is therefore stage 2.
- A: Stage 1 needs a CD4 count of 500 cells/µL or more.
- C: Stage 3 needs a count below 200 cells/µL or a defining illness.
- D: Stage 0 needs a documented negative test within the previous 180 days.
Question 6 · Hard
For a single-platform CD4 count, 50 µL of blood is added to a tube containing 48,000 counting beads. The cytometer collects 3,600 CD4-positive T-cell events and 12,000 bead events. What is the absolute CD4 count?
1. A72 cells/µL [0.07 x 10^9/L]
2. B3,200 cells/µL [3.2 x 10^9/L]
3. C288 cells/µL [0.29 x 10^9/L]
4. D14,400 cells/µL [14.4 x 10^9/L]
Answer and explanation in LearnFree account
Question 7 · Hard
A 38-year-old man with newly diagnosed HIV has Pneumocystis jirovecii pneumonia. His CD4 count is 260 cells/µL [0.26 x 10^9/L], 16% of lymphocytes. How is his infection staged?
1. AStage 0, as the diagnosis is new
2. BStage 2, based on the CD4 count alone
3. CStage 3, because of the opportunistic illness
4. DStage 2, based on the CD4 percentage
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Question 8 · Medium
Infants with 22q11.2 deletion (DiGeorge) syndrome, a conotruncal heart defect, low calcium and a small or absent thymus typically have:
1. ALow T cells with normal B-cell numbers
2. BAbsent B cells with normal T-cell numbers
3. CLow neutrophils with a normal lymphocyte count
4. DLow complement C3 with normal lymphocytes
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Question 9 · Medium
Boys with X-linked (Bruton) agammaglobulinemia usually stay free of serious infection until about 6 months of age. Why?
1. ATheir B cells fail only after 6 months
2. BTheir T cells take 6 months to mature
3. CBreast-milk IgA is absorbed into their blood
4. DMaternal IgG protects them until it wanes
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Question 10 · Hard
A 10-month-old boy has eczema, bloody diarrhea and repeated ear infections. Platelets are 38 x 10^3/µL [38 x 10^9/L] with MPV 5.6 fL (reference 7.5-11.5). IgM is low, IgG is normal, and IgA and IgE are raised. What is the most likely diagnosis?
1. AWiskott-Aldrich syndrome
2. BHyper-IgE syndrome
3. CX-linked agammaglobulinemia
4. DImmune thrombocytopenia
Answer and explanation in LearnFree account

Immunodeficiency: hereditary and acquired

X-linked SCID is caused by mutations in the common gamma chain shared by several interleukin receptors. Which lymphocyte profile is typical?

Universal newborn screening for severe combined immunodeficiency (SCID) in the United States is based on measuring:

Under the CDC surveillance staging of HIV infection for people aged 6 years and older, a CD4 count of 350 cells/µL [0.35 x 10^9/L] with no opportunistic illness is:

For a single-platform CD4 count, 50 µL of blood is added to a tube containing 48,000 counting beads. The cytometer collects 3,600 CD4-positive T-cell events and 12,000 bead events. What is the absolute CD4 count?

A 38-year-old man with newly diagnosed HIV has Pneumocystis jirovecii pneumonia. His CD4 count is 260 cells/µL [0.26 x 10^9/L], 16% of lymphocytes. How is his infection staged?

Infants with 22q11.2 deletion (DiGeorge) syndrome, a conotruncal heart defect, low calcium and a small or absent thymus typically have:

Boys with X-linked (Bruton) agammaglobulinemia usually stay free of serious infection until about 6 months of age. Why?

A 10-month-old boy has eczema, bloody diarrhea and repeated ear infections. Platelets are 38 x 10^3/µL [38 x 10^9/L] with MPV 5.6 fL (reference 7.5-11.5). IgM is low, IgG is normal, and IgA and IgE are raised. What is the most likely diagnosis?