Board Review for March 22

Non-WBC Components of Immunology & Immune Disorders

3.22.2022​

Multiple Choice

A 10-month old infant born at 39 weeks gestation has had recurrent infections over the last several months. The pediatrician identifies an immunodeficiency in this patient.

Which of the following immunoglobulins crosses the placenta and may have offered passive immunity during the neonatal period.

• IgA

• IgD

• IgE

• IgG

• IgM

​IgG

​

Maternal IgG is the only antibody that crosses the placenta in significant amounts.​

• ​Occurs via endocytosis

• Offers Passive Immunity

• Functions via ​binding pathogens, activating complement

Incorrect Answers

​

• IgA = secretory immunoglobulin, activates complement

• ​IgD = antigen receptor, regulates B cells

• IgE = ​Binds basophils and mast cells --> histamine, leukotriene release

• IgM = ​first antibody released after infection, binds and activates complement

Multiple Choice

 Infectious Diseases & Immunology Question 32

A neonatology fellow and neonatologist are discussing the immunoglobulin concentrations in infants over time.

By what postnatal age does maternal IgG typically disappear in the neonatal circulation? 

• Birth

• Two Months

• Six Months

• Nine Months

• Twelve Months

​Maternal IgG Typically Disappears By 9 Months.

• ​IgG is actively transported at start of 2nd trimester

• Done by pinocytosis --> endosomal pathway and acidification --> Fc receptor binding --> release in neonatal serum

• Accelerates during 3rd trimester (levels higher than in mom!)

• No other Ig transported​

​Maternal IgG Typically Disappears By 9 Months.

• Almost all of the maternal IgG disappears from the infant’s circulation by 9 months of age. 

• IgM reaches adult levels by 1 year of age

• No fetal IgA production and levels at 1 year are about 20% of adult

​References:

Brodsky D, Martin C.  Neonatology Review.  2nd edition. Lulu. 2010

Stiehm ER, Ochs HD, Winklestein JA, Rich E (eds).  Immunologic Disorders in Infants and Children. 5th edition. Philadelphia: WB Saunders Company; 2004

Multiple Choice

 Infectious Diseases & Immunology Question 14

A 2-month old infant is admitted to a pediatric hospital for treatment of pneumonia.  At one month of age he had required intravenous antibiotics for an omphalitis.  The pediatric resident is concerned because the infant’s umbilical cord is still present. She asks the neonatologist for advice. 

Of the following, the MOST likely etiology of the infant’s delayed cord separation is:

• Chédiak-Higashi syndrome

• Chronic granulomatous disease

• Hyper-immunoglobulin E syndrome

• Kostmann syndrome

• Leukocyte Adhesion Deficiency

​Leukocyte Adhesion Deficiency

• ​Defect in adhesion, secondary to a defect in beta2-integrins (LAD-1) or sialyl-Lewis-X (LAD-2)

• ​Present with recurrent bacterial infections, poor wound healing, necrotic lesions

• Delayed separation of the umbilical cord

• High risk for omphalitis

​Incorrect Answers

Multiple Choice

Infectious Diseases & Immunology Question 49

Which of the following statements about immunoglobulin levels in neonates is FALSE?

• Maternal IgG is not usually detectable in an infant’s bloodstream at 4 months of age

• Maternal IgG is transported across the placenta to the fetus by endocytosis

• Neonatal IgA levels reach approximately 20% of adult levels by 1 year of age

• Neonatal IgM levels reach approximately 75% of adult levels by 1 year of age

• Peak maternal IgG levels in neonatal blood occur at approximately 40 weeks’ gestation

​Maternal IgG is not usually detectable in an infant’s bloodstream at 4 months of age

• ​Maternal IgG remains in an infant’s bloodstream for more than 6 months of age and is not usually detectable at 9 months of age. 

• Maternal IgG is transported across the placenta to the fetus by endocytosis.

• Neonatal IgA levels reach approximately 20% of adult levels by 1 year of age. 

• Neonatal IgM levels reach approximately 75% of adult levels by 1 year of age.  Peak maternal IgG levels in neonatal blood occur at approximately 40 weeks’ gestation.   

Multiple Choice

Infectious Diseases & Immunology Question 50

When does IgA production begin?

• At Birth

• At 2 months’ gestation

• At 4 months’ gestation

• At 6 months’ gestation

• At 8 months’ gestation

​IgA Production Starts at Birth

Multiple Choice

Infectious Diseases & Immunology Question 53

A neonate has just been diagnosed with a Neisseria infection. You are worried about a complement deficiency. All of the following is true about the complement system, EXCEPT:

• C2 is the most common complement deficiency

• C4 is part of the alternative pathway

• Deficiency of late components results in an increased risk of a Neisseria infection

• Most neonates reach adult complement levels at 3 to 6 months of age

• The classical pathway requires antigen-antibody reaction

​Complement Pathways

​Classical

• ​Starts with formation of antibody-antigen complex

• ​C1--> C4--> C2--> C3 --> MAC

Alternative

• C3b protein binds a microbe, foreign material, or damaged tissue​

Lectin

• Starts with binding of mannose from bacterial surfaces​

Multiple Choice

Infectious Diseases & Immunology Question 54

All of the following are components of the innate immune system, EXCEPT:

• B Lymphocyte

• Complement

• Eosinophils

• Neutrophils

• Skin and mucous membranes

Multiple Choice

Infectious Diseases & Immunology Question 59

What is the most common form of immune dysfunction found in patients with chromosome 22q11.2 deletion?

• Graft versus Host Disease

• Oligoclonal peripheral T-cell proliferation

• Severe immunoglobulin deficiency

• T cell hypoplasia and mild to moderate peripheral lymphopenia

• Thymic aplasia and severe T-cell lymphopenia

T cell hypoplasia with peripheral lymphopenia

Multiple Choice

Infectious Diseases & Immunology Question 75

The state you practice in recently started a newborn screening program for severe combined immunodeficiency (SCID). What is the most likely molecular basis for the newborn screening test for SCID?

• Detection by PCR of DNA fragments that are excised during T-cell receptor rearrangement

• Detection of adenosine deaminase deficiency by mass spectrometry

• Detection of adenylate kinase deficiency by mass spectrometry

• Detection by PCR of recombinase activating genes

• Identification of defects in the IL-2 receptor gamma-common chain

Multiple Choice

Infectious Diseases & Immunology Question 76

You are taking care of an infant diagnosed prenatally with tetralogy of Fallot. He was born at 39 WGA via vaginal delivery. The infant has no radiographic thymic shadow and a borderline low serum calcium level. You suspect that this infant might have DiGeorge syndrome so you consult the Genetics team and send a FISH to detect a possible 22q11.2 deletion. While you are awaiting the results of the genetic testing, the newborn screen results come back positive for severe combined immunodeficiency (SCID).

What is the next step to confirm the diagnosis of DiGeorge syndrome in this vignette?

• Assess lymphocyte subsets by flow cytometry and T-cell function by proliferation assay

• Send a complete blood cell count to assess the infant’s lymphocyte count

• Send a repeat serum calcium level

• Send blood for complement C3 and C4 levels

• No further tests required

Multiple Choice

Infectious Diseases & Immunology Question 77

You are taking care of a 7-day old infant born at term who was recently diagnosed with complete DiGeorge syndrome. The infant develops lymphadenopathy and an erythematous, diffuse scaly rash covering his whole body. An oligoclonal T-cell population in the blood was identified and T-cell receptor excision circles (TRECs) were not measurable.

What is the most appropriate treatment of the infant in this vignette?

• Systemic antibiotics

• Systemic antifungals

• Systemic steroids and thymus transplantation

• Topical treatment with hydrating cream

• Topical treatment with steroids

​Partial versus Complete DiGeorge

​Partial

Complete

• Majority of patients

• Hypoplastic thymus

• ​Low number of T cells

• T cells can proliferate normally ​

• Treatment: Supportive, time​

• Rare

• Thymic aplasia

• Atypical form = ​eczematous rash associated with lymphadenopathy (oligoclonal expansion of peripheral T-cells)

• ​Treatment: systemic corticosteroids

Multiple Choice

Infectious Diseases & Immunology Question 78

You are speaking with the parents of an infant who was recently diagnosed with DiGeorge syndrome. You are explaining that most children with this syndrome have an impaired immune system.

Which of the following statements is FALSE about the immunodeficiency in DiGeorge syndrome?

• Patients are at high risk for the development of disseminated infections

• Patients have a depressed T-cell function

• Patients may present with graft-versus-host disease

• Patients often have low immunoglobulin levels

• The lack of T-cells in the periphery is explained by lack of precursor T-cells

Multiple Choice

A 2-week old neonate is brought to your attention because his umbilical cord is still attached and the area around the cord is red. The pregnancy had been uncomplicated and the infant was born at term by spontaneous vaginal delivery. The infant’s parents recently immigrated to the US and are consanguineous. This is their first child. After obtaining a complete blood cell count (CBC) and a blood culture in the infant, you start antibiotic therapy. The CBC returns with marked neutrophilia.

What is the most likely pathogenesis of this infant’s disease?

• B-cell deficiency

• Combined severe immune deficiency

• Mutations in the β2 integrin gene leading to neutrophil dysfunction

• T-cell deficiency

• None of the above

​Leukocyte Adhesion Deficiency

• ​Defect in adhesion, secondary to a defect in beta2-integrins (LAD-1) or sialyl-Lewis-X (LAD-2)

• ​Present with recurrent bacterial infections, poor wound healing, necrotic lesions

• Delayed separation of the umbilical cord

• High risk for omphalitis

Multiple Choice

Infectious Diseases & Immunology Question 81

You are caring for an infant with heterotaxy-asplenia.  As a precaution, you initiate antibiotic prophylaxis to prevent infection by encapsulated organisms. 

Which of the following is NOT an encapsulated organism?

• Haemophilus influenza

• Neisseria meningitidis

• Pseudomonas aeruginosa

• Salmonella typhi

• Streptococcus pneumoniae

Multiple Choice

Infectious Diseases & Immunology Question 82

The spleen plays many important physiologic roles. 

Of the following, the function that is NOT associated with the spleen is:

• Assisting the functional maturation of antibodies

• Helping the body excrete excess iron

• Producing immunoglobulin (IgM) and complement

• Removing abnormal red blood cells and platelets from the circulation

• Supporting the proliferation of T-cells

​Functions of the Spleen

• ​Site of IgM and complement production

• Assists in maturation of antibodies

• Supports proliferation of T-cells

• Scavenges damaged or old RBCs & platelets

• Serves as reservoir of blood

• Recycles, rather than excretes, iron from hemoglobin for use in hematopoeisis

Multiple Choice

Question 83

Each of the following disorders can be associated with congenital asplenia EXCEPT:

• Ivemark syndrome

• Pearson Syndrome

• Sickle Cell Disease

• Smith-Meyers-Fineman syndrome

• Stormorken syndrome

Sickle Cell Disease is associated with functional asplenia

• Sickle cell disease is a hemoglobinopathy that causes red blood cells to sickle under certain conditions. 

• Over time, the spleen autoinfarcts, making patients with sickle cell disease functionally asplenic.

​

​Condition	​Description
​Ivemark syndrome	​Autosomal Recessive. Characterized by asplenia or splenic hypoplasia, heterotaxy, and cardiac anomalies.
​Pearson syndrome	​Bone marrow failure syndrome --> sideroblastic anemia, thrombocytopenia. Asplenia can be associated.  Stormorken syndrome is also a rare disease that consists of asplenia and thrombocytopenia, among other feature
​Stormorken syndrome	​Characterized by tubular aggregate myopathy. Presents with asplenia, thrombocytopenia, muscle weakness.
​Smith-Meyers-Fineman syndrome	​ X-linked recessive. Involves asplenia, cryptorchidism, and severe intellectual impairment.

Multiple Choice

Infectious Diseases & Immunology Question 84

You are concerned that an infant in the Neonatal Intensive Care Unit has an absent or non-functioning spleen.  The finding on a peripheral blood smear MOST specific for splenic dysfunction is:

• Heinz Bodies

• Howell-Jolly bodies

• Pappenheimer bodies

• Reticulocytes

• Thrombocytosis

​Finding	​Description​	​Association
​Howell Jolly Bodies	​Small, round	​Asplenia
​Heinz Bodies	​Small red or pink dots that are denatured hemoglobin inclusions, more	​G6PD; Thalassemia
​Pappenheimer bodies	small blue or purple basophilic granules that contain	​Sideroblastic anemia

​Reticulocytosis and thrombocytosis are nonspecific findings in asplenia.

​Howell Jolly Bodies

​Heinz Bodies

Multiple Choice

Infants and children lacking functioning spleens are at increased risk for infections. 

Which of the following statements about immunizing children with asplenia is TRUE?

• Asplenic children cannot receive any live virus immunizations.

• Asplenic infants should wait at least 6 months prior to receiving any vaccinations

• Children should receive the 13-valent Pneumococcal vaccine as well as the 23-valent vaccine after age 2

• Children with asplenia are not at increased risk for viral infections and therefore should not receive influenza vaccination

• The meningococcal vaccine is only recommended for special subpopulations of children with asplenia, such as those living in shelters or dormitories

• Need to receive both pneumococcal vaccines (PCV13 and PPSV23)

• PCV13 is first: currently a 4 dose series for all kids at 2, 4, 6 and 12-15 months

• After age 2, kids with asplenia also need​

  • 2 doses of PCV13 if they are unvaccinated <3 doses. Give the second dose at least 8 weeks after the first.

  • Give 1 dose of PCV13 if they received 3 doses of PCV13 but none were given after 12 months of age.

  • Give 2 doses of PPSV23 after the PCV13 series is complete. Give the first dose at least 8 weeks after any prior PCV13 dose, then give the second dose of PPSV23 at least 5 years after the first PPSV23 dose.

​Asplenic patients are at high risk for infection from encapsulated bacteria, including pneumococcus.

​Incorrect Answers

• Children with no or non-functioning spleens should receive the typical schedule of childhood vaccinations. 

• Also need meningitis vaccines (encapsulated bacteria)

• No changes to viral vaccines either

Multiple Choice

Infectious Diseases & Immunology Question 101

An infant is been monitored in the NICU for several months with recurrent, severe purulent bacterial and fungal infections.  The nitroblue tetrazolium (NBT) test is performed and is negative.

The infant described in this vignette most likely has:

• Chediak-Higasi syndrome

• Chronic granulomatous disease

• Leukocyte adhesion deficiency

• Neutropenia

• SCID

Remember this table?​

​Classic test for CGD is the nitroblue tetrazolium test (NBT) test.

Multiple Choice

Infectious Diseases & Immunology Question 103

All of the following compounds are collectins, EXCEPT

• Conglutinin

• Mannan-binding lectin (MBL)

• Surfactant protein-A

• Surfactant protein-B

• Surfactant protein-D

Collectins

• Family of soluble oligomeric proteins in the innate immune system

• Collagenous ​Ca²⁺-dependent defense lectins

• Function is to bind to oligosaccharide structure or lipids that are on the surface of microorganisms

• --> elimination by complement activation, aggregation, opsonization, etc.

Nine Types of Collectins Have Been Identified

• Mannose Binding Lectin

• SP-A

• SP-D

• Collectin liver 1

• Collectin placenta 1

• Conglutinin collectin of 43 kDa​

• Collectin of 46 kDa​​

• Collectin kidney 1​

• Conglutinin

​SP-B is NOT a collectin.

​The End.

​References

1. Bedocs LA, O’Regan GM, Bruckner A. Red, scaly babies: neonatal erythroderma. NeoReviews. 2011;12: e325-e334

2. Selim MA, Markert ML, Burchette JL, et al. The cutaneous manifestations of atypical complete DiGeorge syndrome: a histopathologic and immunohistochemical study. J Cutan Pathol. 2008;35:380-385

3. Brodsky & Martin's Neonatology Review. 2nd Edition. 2010

4. Stiehm, Ochs, Winklestein, Rich (eds). Immunologic Disorders in Infants and Children, 5th edition. 2004.

5. David A. Randolph; The Neonatal Adaptive Immune System. Neoreviews October 2005; 6 (10): e454–e462.

6. Randolph DA, Routes JM, Verbsky JW. Newborn screening for severe combined immunodeficiency. NeoReviews. 2013;14:e448-e455

7. Medzhitov R, Janeway C. Innate immunity. N Engl J Med. 2000;343:338-344

8. Bobey-Wright NAM, Tcheurekdjian H, Wara D, Lewis DB. Immunologic aspects of DiGeorge syndrome. NeoReviews. 2005; 6:e471-e478

​9. Anderson JM, Philip AGS. Management of the umbilical cord: care regimens, colonization, infection, and separation. NeoReviews. 2004;5:e155-e16

10. Parvaneh N, Mamishi S, Rezaei A, et al. Characterization of 11 new cases of leukocyte adhesion deficiency type 1 with seven novel mutations in the ITGB2 gene. J Clin Immunol. 2010;30:756-760

11. Styrt B. Infection associated with asplenia: Risks, mechanisms, and prevention. Am J Med. 1990;88:33N-42N

12. Behrman RE, Kliegman RM, Jenson HB (eds). The hematopoietic system. In: Nelson’s Textbook of Pediatrics. 17th edition. Philadelphia: Saunders, 2004

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