A 41-year-old woman on hemodialysis is on the kidney transplant waiting list. Two weeks ago she completed a desensitization course of intravenous immunoglobulin (IVIG), 2 g/kg, and she has had no transfusions, vaccines or illness since. Her routine 6-monthly serology is compared with the previous set. Six months ago: CMV IgG negative, varicella-zoster virus (VZV) IgG negative, anti-HBs below 2 mIU/mL despite a full vaccine course, total anti-HBc nonreactive. Now: CMV IgG positive at a low level, CMV IgM negative, VZV IgG positive, anti-HBs 38 mIU/mL, total anti-HBc reactive (S/CO 1.8; reactive at 1.0 or more), HBsAg nonreactive and HBV DNA not detected. The most likely explanation for the new results is:

Passive IgG transferred in the IVIG

A late response to hepatitis B vaccine

Past, resolved hepatitis B infection

The antigen-binding site of an antibody is formed by the:

Heavy and light chain variable regions

Hinge region of the heavy chains

Two heavy chain constant regions

J chain and secretory component

Pepsin digestion of IgG leaves a fragment that can still agglutinate particles carrying the antigen. That fragment is:

F(ab')2, with two linked binding sites

Fab, with a single binding site

Fc, made of heavy chain constant domains

Free light chains, kappa or lambda

Antibodies and antigen-antibody reactions

13 DOH Abu Dhabi (HAAD) lab licensing practice questions on Antibodies and antigen-antibody reactions, part of Immunology and Serology. The first 13 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 41-year-old woman on hemodialysis is on the kidney transplant waiting list. Two weeks ago she completed a desensitization course of intravenous immunoglobulin (IVIG), 2 g/kg, and she has had no transfusions, vaccines or illness since. Her routine 6-monthly serology is compared with the previous set. Six months ago: CMV IgG negative, varicella-zoster virus (VZV) IgG negative, anti-HBs below 2 mIU/mL despite a full vaccine course, total anti-HBc nonreactive. Now: CMV IgG positive at a low level, CMV IgM negative, VZV IgG positive, anti-HBs 38 mIU/mL, total anti-HBc reactive (S/CO 1.8; reactive at 1.0 or more), HBsAg nonreactive and HBV DNA not detected. The most likely explanation for the new results is:
1. ARecent primary CMV infection
2. BA late response to hepatitis B vaccine
3. CPassive IgG transferred in the IVIG
4. DPast, resolved hepatitis B infection
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Answer: C · Passive IgG transferred in the IVIG
IVIG is IgG pooled from thousands of donors, so it carries the IgG antibodies common in the donor population, including anti-CMV, anti-VZV, anti-HBs and sometimes anti-HBc. Several IgG markers turning positive at once, straight after the infusion, with no IgM, no symptoms, no HBsAg and no HBV DNA, fits passive transfer rather than several new infections. IVIG contains almost no IgM, which is why CMV IgM stays negative; a primary CMV infection would usually give IgM and would not explain the other changes. Resolved hepatitis B and a late vaccine response each explain only the HBV markers, and a vaccine response never produces anti-HBc. Passive IgG falls with a half-life of about 3 weeks, so the serology should be repeated months later, and NAT used if an infection must be excluded now.
- A: A primary CMV infection usually gives IgM and does not explain the VZV or HBV changes.
- B: Vaccination never produces anti-HBc and would not explain the CMV or VZV results.
- D: Resolved hepatitis B would not explain new CMV and VZV IgG at the same time.
Question 2 · Easy
The antigen-binding site of an antibody is formed by the:
1. AHinge region of the heavy chains
2. BTwo heavy chain constant regions
3. CJ chain and secretory component
4. DHeavy and light chain variable regions
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Answer: D · Heavy and light chain variable regions
Each arm of the Y-shaped molecule (the Fab) pairs the variable domain of a heavy chain with that of a light chain. Three hypervariable loops, the complementarity-determining regions, from each chain form the pocket that fits the epitope. A basic IgG molecule therefore has two identical binding sites. The Fc portion, made of heavy chain constant domains, carries the effector functions.
- A: The hinge gives the arms flexibility but does not bind antigen.
- B: The heavy chain constant regions form the Fc, which carries effector functions.
- C: The J chain and secretory component link and protect polymeric IgA and IgM; they do not bind antigen.
Question 3 · Medium
Pepsin digestion of IgG leaves a fragment that can still agglutinate particles carrying the antigen. That fragment is:
1. AFab, with a single binding site
2. BFc, made of heavy chain constant domains
3. CF(ab')2, with two linked binding sites
4. DFree light chains, kappa or lambda
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Answer: C · F(ab')2, with two linked binding sites
Pepsin cuts IgG below the disulfide bonds of the hinge, leaving one F(ab')2 fragment with both binding sites still joined, while the Fc is broken into small peptides. Because F(ab')2 is bivalent, it can cross-link antigen and cause agglutination or precipitation. Papain cuts above the hinge instead, giving two separate univalent Fab fragments and an intact Fc. F(ab')2 reagents are useful because, without an Fc, they do not bind Fc receptors or activate complement.
- A: Fab fragments come from papain and have only one binding site, so they cannot cross-link.
- B: The Fc has no antigen-binding site, and pepsin breaks it into small peptides.
- D: Pepsin does not release free light chains, and light chains alone bind antigen poorly.
Question 4 · Hard
A newborn has a passively acquired maternal IgG antibody with a titer of 1:64 at birth. Assuming an IgG half-life of 21 days and no antibody production by the infant, what titer is expected at 63 days of age?
1. A1:8
2. B1:32
3. C1:4
4. D1:16
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Answer: A · 1:8
63 days is 63 / 21 = 3 half-lives. Each half-life halves the antibody concentration, which lowers the titer by one twofold dilution: 1:64 to 1:32 to 1:16 to 1:8. Overall, 1/2 x 1/2 x 1/2 = 1/8 of the antibody remains, and 64 / 8 = 8. A titer that stays level or rises instead suggests that the infant is making the antibody, which can point to infection.
- B: 1:32 is the titer after only one half-life (21 days).
- C: 1:4 would need four half-lives (84 days).
- D: 1:16 is the titer after two half-lives (42 days).
Question 5 · Easy
Which immunoglobulin class is present at the highest concentration in the serum of a healthy adult?
1. AIgG
2. BIgE
3. CIgM
4. DIgA
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Answer: A · IgG
IgG makes up about 70-75% of serum immunoglobulin, around 7-16 g/L in adults; IgA is next at about 15%, then IgM at about 10%, with IgD and IgE present only in trace amounts. The long half-life of IgG, about 3 weeks, helps keep its level high. It dominates the secondary response and is the only class that crosses the placenta in useful amounts. A low IgG is the main finding in most antibody deficiencies.
- B: IgE is present only in trace amounts in serum, mostly bound to mast cells.
- C: IgM makes up only about 10% of serum immunoglobulin.
- D: IgA is second in serum, although it is the main class in secretions.
Question 6 · Medium
Small inherited differences in the constant region of IgG between people, such as Gm markers, are called:
1. AIsotypes
2. BIdiotypes
3. CAllotypes
4. DSubclasses
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Question 7 · Medium
In the prozone phenomenon, an agglutination test is falsely negative because:
1. AAntigen excess fills every antibody binding site
2. BSerum complement lyses the indicator particles
3. CAntibody excess prevents cross-linking of particles
4. DIgG is too small to bridge the particles
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Question 8 · Hard
A manufacturer compares two monoclonal antibodies to capture a hormone present at very low levels. Antibody X has a dissociation constant (Kd) of 1 x 10^-10 mol/L; antibody Y has a Kd of 1 x 10^-7 mol/L. Which should be chosen?
1. AY, because its higher Kd means higher affinity
2. BY, because faster release lowers the background
3. CEither one, because Kd does not affect sensitivity
4. DX, because its lower Kd means higher affinity
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Question 9 · Easy
A small molecule, such as penicillin, that can bind antibody but cannot trigger antibody production unless it is attached to a carrier protein is called:
1. AAn epitope
2. BA hapten
3. CA mitogen
4. DAn adjuvant
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Question 10 · Medium
IgG made several weeks after immunization binds the antigen more tightly than the IgG made in the first days. This rise in affinity results from:
1. ASomatic hypermutation and B-cell selection
2. BBinding of complement to the antibody
3. CMore plasma cells making antibody
4. DClass switching from IgM to IgG
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Question 11 · Easy
The class (isotype) of an immunoglobulin, such as IgG or IgA, is set by its:
1. AVariable regions
2. BHinge region length
3. CHeavy chain constant region
4. DLight chain constant region
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Question 12 · Hard
A patient has been ill for 6 weeks, and the causative organism has grown in blood culture. A slide agglutination test for antibodies to it is negative on undiluted serum. What should the technologist do before reporting?
1. AHeat the serum at 56 °C and retest it
2. BExtend the reading time to 10 minutes
3. CRetest the serum at a series of dilutions
4. DReport negative and ask for a repeat in 2 weeks
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Question 13 · Medium
Compared with a polyclonal antiserum, a monoclonal antibody reagent:
1. AContains antibodies to many epitopes
2. BVaries in specificity from batch to batch
3. CIs harvested from an immunized animal's serum
4. DBinds one epitope with uniform specificity
Answer and explanation in LearnFree account

Antibodies and antigen-antibody reactions

The antigen-binding site of an antibody is formed by the:

Pepsin digestion of IgG leaves a fragment that can still agglutinate particles carrying the antigen. That fragment is:

A newborn has a passively acquired maternal IgG antibody with a titer of 1:64 at birth. Assuming an IgG half-life of 21 days and no antibody production by the infant, what titer is expected at 63 days of age?

Which immunoglobulin class is present at the highest concentration in the serum of a healthy adult?

Small inherited differences in the constant region of IgG between people, such as Gm markers, are called:

In the prozone phenomenon, an agglutination test is falsely negative because:

A manufacturer compares two monoclonal antibodies to capture a hormone present at very low levels. Antibody X has a dissociation constant (Kd) of 1 x 10^-10 mol/L; antibody Y has a Kd of 1 x 10^-7 mol/L. Which should be chosen?

A small molecule, such as penicillin, that can bind antibody but cannot trigger antibody production unless it is attached to a carrier protein is called:

IgG made several weeks after immunization binds the antigen more tightly than the IgG made in the first days. This rise in affinity results from:

The class (isotype) of an immunoglobulin, such as IgG or IgA, is set by its:

A patient has been ill for 6 weeks, and the causative organism has grown in blood culture. A slide agglutination test for antibodies to it is negative on undiluted serum. What should the technologist do before reporting?

Compared with a polyclonal antiserum, a monoclonal antibody reagent: