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Test Bank
Abbas: Basic Immunology, 4thEdition
Chapter 12: Congenital and Acquired Immunodeficiencies
Test Bank
MULTIPLE CHOICE
1.All of the following may result in an acquired immunodeficiency EXCEPT:
A.Malnutrition
B.Treatment with corticosteroids
C.Disseminated cancer
D.Inherited defect in B cell maturation
E.Infection with human immunodeficiency virus (HIV)
ANS: D
An inherited defect in B cell maturation is, by definition, a primary immunodeficiency, not an acquired immunodeficiency. In particular, abnormalities in B lymphocyte development and function result in deficient antibody production and increased susceptibility to infection by extracellular microbes. In contrast, malnutrition, treatment with corticosteroids, disseminated cancer, and infection with human immunodeficiency virus (HIV) would all result in acquired, or secondary, immunodeficiencies. Administration of corticosteroids to intentionally create an immunosuppressive state, such as in the treatment of inflammatory diseases or the prevention of tissue allograft rejection, is referred to as iatrogenic immunosuppression.
2.Which one of the following is typically NOT associated with T cell immunodeficiencies?
A.Cancer
B.Viral infection
C.Autoimmunity
D.Infection with intracellular microbes
E.Infection with pyogenic bacteria
ANS: E
B cell, not T cell, immunodeficiencies are associated with increased incidence of infection with pyogenic bacteria. In contrast, increased incidence of cancer is most often seen in T cell immunodeficiencies, because T cells are critical for surveillance against oncogenic viruses and the tumors they cause. Defects in cell-mediated immunity lead to infection by viruses and other intracellular microbes. Interestingly, certain immunodeficiencies are associated with increased incidence of autoimmunity; the mechanism for this phenomenon may reflect a deficiency of regulatory T cells that normally serve to maintain self-tolerance.
3. A 7-month-old boy is evaluated in the clinic for recurrent bacterial infections. His tonsils are not visible on physical examination. Serum immunoglobulin A (IgA) and IgG levels are markedly decreased, and serum IgM levels are slightly below normal. Based on the findings described, which one of the following should be excluded from the differential diagnosis?
A.X-linked agammaglobulinemia
B.X-linked severe combined immunodeficiency disease (X-linked SCID)
C.Common variable immunodeficiency
D.X-linked hyper-IgM syndrome
E.Adenosine deaminase deficiency (ADA)
ANS: D
The infant’s presentation suggests an underlying congenital immunodeficiency. X-linked hyper-IgM syndrome is characterized by failure of the B cell heavy chain to undergo switching from the IgM isotype, excess levels of IgM antibody (hyper-IgM) are often detectable in sera from patients. Thus, these patients are predisposed to both pyogenic and protozoal infections. X-linked severe combined immunodeficiency disease (SCID) and adenosine deaminase (ADA) deficiency are both forms of SCID and will present as very low levels of T cell–dependent Ig isotypes (IgG and IgA), as well as defects in cell-mediated immunity. X-linked agammaglobulinemia is a defect in B cell maturation and will present as very low levels of all antibody isotypes. Common variable immunodeficiency includes a number of defects in B cell differentiation into antibody-secreting cells and may present as pan-Ig deficiency.
4. A 7-month-old boy is evaluated in the clinic for recurrent bacterial infections. His tonsils are not visible on physical examination. Serum immunoglobulin A (IgA) and IgG levels are markedly decreased, and serum IgM levels are slightly below normal. Careful examination of this infant reveals white plaques along the buccal mucosa, palate, and tongue, consistent with oral candidiasis (thrush). Analysis of blood cells reveals normal numbers of B cells and very few CD3+ cells. In addition, maternally-derived T cells, as determined by HLA typing, are detectable. The infant’s mother reports that two of her three brothers died of infection as young children. Collectively, this presentation and history are most consistent with which of the following disorders?
A.X-linked agammaglobulinemia
B.X-linked severe combined immunodeficiency disease (X-linked SCID)
C.Common variable immunodeficiency
D.X-linked hyper-IgM syndrome
E.Adenosine deaminase deficiency (ADA)
ANS: B
Oral candidiasis suggests impaired cell-mediated immunity, and a low number of CD3+ cells implies a defect in T cell maturation. The persistence of transplacentally-derived maternal T cells also implies a lack of cell-mediated immunity in the child, because these T cells will express MHC alleles not inherited by the child and should therefore be recognized and eliminated by him. The information presented in Question 5 indicates that the infant also exhibits signs and symptoms consistent with humoral immunodeficiency. This pattern of severe combined immunodeficiency (SCID) can be caused by both X-linked SCID and by adenosine deaminase (ADA) deficiency, which is an autosomal recessive disease. The patient’s family history is highly suggestive of an X-linked recessive pattern of inheritance: the infant is male, and two of his maternal uncles died in childhood of possible infections. His clinical picture is therefore most consistent with X-linked SCID, the predominant cause of severe combined immunodeficiency, occurring in approximately 50% of cases.
5. A 7-month-old boy is evaluated in the clinic for recurrent bacterial infections. His tonsils are not visible on physical examination. Serum immunoglobulin A (IgA) and IgG levels are markedly decreased, and serum IgM levels are slightly below normal. Based on this family’s history and clinical presentation, a mutation in which of the following genes is most likely to be found in this patient?
A.JAK3 kinase
B.Adenosine deaminase
C.Common cytokine receptor chain
D.RAG2
E.Purine nucleoside phosphorylase
ANS: C
X-linked severe combined immunodeficiency disease (SCID) results from mutations in the gene encoding the cytokine receptor common chain. Mutations in any of the other genes listed (JAK3 kinase, adenosine deaminase, RAG2, or purine nucleoside phosphorylase) cause severe combined immunodeficiency syndrome with autosomal recessive patterns of inheritance.
6. A 7-month-old boy is evaluated in the clinic for recurrent bacterial infections. His tonsils are not visible on physical examination. Serum immunoglobulin A (IgA) and IgG levels are markedly decreased, and serum IgM levels are slightly below normal. The gene identified in this patient plays a critical role in receptor binding to all of the following ligands EXCEPT:
A.Interleukin (IL)-2
B.IL-4
C.IL-7
D.IL-12
E.IL-15
ANS: D
The common chain protein is shared by receptors for the interleukins (IL)-2, IL-4, IL-7, IL-9, and IL-15.
7. A 7-month-old boy is evaluated in the clinic for recurrent bacterial infections. His tonsils are not visible on physical examination. Serum immunoglobulin A (IgA) and IgG levels are markedly decreased, and serum IgM levels are slightly below normal. This infant should NOT be given the measles-mumps-rubella (MMR) vaccination because:
A.The vaccine would have no effect because he is not susceptible to infection with measles, mumps, or rubella.
B.The vaccine would have no effect because he cannot mount an appropriate humoral response.
C.The vaccine could be dangerous because he is predisposed to develop a type I hypersensitivity response to the MMR vaccine.
D.The vaccine could be dangerous because vaccination with MMR would put him at risk for developing a fatal infection.
E.Vaccination with MMR is not contraindicated in his case and should be performed to prevent future infection.
ANS: D
The measles-mumps-rubella (MMR) preparation is a live, attenuated viral vaccine. The great advantage of this type of vaccine is that it elicits all the innate and adaptive immune responses that would naturally arise as a result of infection with the pathogenic viruses. As such, it is the ideal way of inducing protective immunity. Nevertheless, whereas the viruses in the vaccine have been manipulated in the laboratory to become nonpathogenic in individuals with intact immune systems, they can potentially cause disease in vulnerable patients, such as those with congenital immunodeficiencies. As such, administration of the MMR vaccine is contraindicated in an infant with X-linked severe combined immunodeficiency disease (SCID), because vaccination would place him at risk of developing fatal infection.
8.A lymph node biopsy from a young boy with X-linked agammaglobulinemia is expected to show which of the following histologic features?
A.Marked perivascular lymphocytic infiltrate
B.Abundant polymorphonuclear inflammation
C.Reduced follicles and germinal centers
D.Nearly absent parafollicular cortical regions
E.Enlarged follicles
ANS: C
X-linked agammaglobulinemia, or Bruton’s agammaglobulinemia, is an immunodeficiency disease characterized by a block in early B cell maturation and absence of serum Ig. As in other B cell deficiencies, morphology of lymphoid tissues is most remarkable for absent or reduced follicles and germinal centers (i.e., the B cell zones). In contrast, T cell deficiencies usually do not affect follicle size, but follicles will lack germinal centers and there may be reduced parafollicular cortical regions (i.e., the T cell zones).
9.Which of the following is the most common known primary immunodeficiency with a prevalence of 1 in 700 white individuals?
A.X-linked agammaglobulinemia
B.Selective IgA deficiency
C.Common variable immunodeficiency
D.Chronic granulomatous disease
E.Chédiak-Higashi syndrome
ANS: B
Selective IgA deficiency is the most common (known) primary immunodeficiency and is believed to affect approximately 1 in 700 white individuals. Most cases occur sporadically. Whereas many patients show no clinical symptoms, others experience occasional respiratory infections and diarrhea. In rare cases, patients present with severe, recurrent infections that lead to permanent intestinal and airway damage, with other associated autoimmune disorders.
10.An 18-month-old girl is brought to the pediatrician because of recurrent upper respiratory tract infections. She has a fever, labored breathing, and a dry cough. Diagnostic tests confirm infection with Pneumocystis jiroveci. Serum studies are remarkable for negligible levels of IgG and IgA in the presence of high concentrations of IgM. The family history is unremarkable; in particular, the patient’s three older brothers are in excellent health. This patient most likely carries a mutation in which of the following molecules?
A.CD18
B.CD40L
C.ZAP-70
D.B7
E.CD40
ANS: E
The patient’s clinical presentation is consistent with hyper-IgM syndrome, which is associated with defective switching of B cells to the IgG and IgA isotypes. Whereas IgG and IgA levels may be undetectable in blood, IgM titers are often concomitantly increased. The molecular defect arises from impaired interaction between CD40L on T cells and CD40 on B cells; thus T cells cannot provide B cells with the stimulatory signals required for heavy chain isotype switching. Patients also show defects in cell-mediated immunity, since CD40 ligand-receptor interactions are important for T cell–dependent activation of macrophages. These patients therefore are particularly susceptible to infection by the opportunistic intracellular microbe Pneumocystis jiroveci. Because this patient is a girl with healthy brothers and maternal uncles, she is unlikely to have X-linked hyper-IgM syndrome, which is caused by mutations in CD40L (expressed on T cells). Rather, she is more likely to carry a rare mutation in CD40 (expressed on B cells), which results in hyper-IgM syndrome with an autosomal recessive pattern of inheritance.
11. A 3-year-old boy is taken to the pediatrician because of a nosebleed (epistaxis). He has a history of severe, recurrent sinopulmonary infection. Physical examination is remarkable for dry, red patches of skin (eczema) and multiple petechiae (tiny hemorrhagic spots). Laboratory findings include thrombocytopenia and reduced IgM levels. The boy’s maternal uncle died of bleeding complications after an emergency appendectomy. Which of the following is the most likely diagnosis?
A.Reticular dysgenesis
B.Wiskott-Aldrich syndrome (WAS)
C.Chédiak-Higashi syndrome
D.Ataxia-telangiectasia
E.DiGeorge syndrome
ANS: B
This patient most likely has Wiskott-Aldrich syndrome (WAS), an X-linked immunodeficiency disease involving multiple organ systems. It is characterized by eczema, a low platelet count (thrombocytopenia), and susceptibility to bacterial infection. Patients with WAS have a mutation in a gene that encodes a cytoplasmic protein expressed exclusively in bone marrow–derived cells. This protein interacts both with adapter molecules, such as Grb-2, and with small G proteins of the Rho family that regulate the actin cytoskeleton. Expression of many cell surface glycoproteins on lymphocytes, macrophages, neutrophils, and platelets is also reduced. All of these changes likely interfere with trafficking of leukocytes to sites of inflammation.
12. A 3-year-old boy is taken to the pediatrician because of a nosebleed (epistaxis). He has a history of severe, recurrent sinopulmonary infection. Physical examination is remarkable for dry, red patches of skin (eczema) and multiple petechiae (tiny hemorrhagic spots). Laboratory findings include thrombocytopenia and reduced IgM levels. The boy’s maternal uncle died of bleeding complications after an emergency appendectomy. Which of the following represents a curative therapy currently available for this patient?
A.Passive immunization with gamma globulin
B.Bone marrow transplantation
C.Treatment with corticosteroids
D.Enzyme replacement
E.Gene therapy
ANS: B
Bone marrow transplantation, in which the immunodeficient patient’s marrow is reconstituted with functional immune cell precursors, is the only curative therapy currently available for Wiskott-Aldrich syndrome (WAS) or severe combined immunodeficiency disease (SCID). In particular, bone marrow transplantation from HLA-matched sibling donors have had very high success rates. Passive immunization with gamma globulin only prevents or minimizes future infections. Corticosteroids, which exhibit immunosuppressive effects, are contraindicated in already immunodeficient patients. Enzyme replacement therapy has shown transient benefit in patients with well-characterized enzyme deficiencies, including adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiencies. Gene therapy to restore the affected WASP gene in WAS syndrome, although potentially curable, remains a distant clinical goal.
13.Which of the following patients is particularly susceptible to infection with Streptococcus pneumoniae, an encapsulated bacterium?
A.A 23-year-old man with malaise, rash, and diffuse lymphadenopathy consistent with early infection with human immunodeficiency virus
B.A 54-year-old woman receiving local corticosteroid injections for knee pain
C.A 35-year-old man with Hodgkin’s disease and a deficient delayed-type hypersensitivity (DTH) response to Candida antigen
D.A 6-year-old boy with sickle cell anemia who had a splenectomy
E.A 77-year-old woman on chronic renal dialysis and a strict low-protein diet
ANS: D
A patient who has undergone splenectomy, or surgical removal of the spleen, is particularly susceptible to infection with encapsulated bacteria such as Streptococcus pneumoniae. This occurs because the spleen is a major site for production of antibodies specific for T cell–independent polysaccharide antigens found in bacterial capsules. In addition, the spleen is important for the phagocytic clearance of opsonized blood-borne microbes.
14.Human immunodeficiency virus (HIV) is NOT a:
A.Herpesvirus
B.RNA virus
C.Enveloped virus
D.Retrovirus
E.Lentivirus
ANS: A
Human immunodeficiency virus (HIV) is a member of the Lentivirus family of retroviruses. Retroviruses are all enveloped RNA viruses. Herpesviruses are a family of DNA viruses, many of which cause human diseases, including Epstein-Barr virus, cytomegalovirus, herpes simplex virus, and varicella.
15.All of the following have a direct role in mediating human immunodeficiency virus (HIV) entry into susceptible cells EXCEPT:
A.CD4
B.MHC class I
C.CCR5
D.CXCR4
E.Env
ANS: B
Human immunodeficiency virus (HIV) entry into host cells occurs when gp120, a glycoprotein expressed on the HIV envelope, binds to CD4 expressed on host T cells. This induces a conformational change in gp120, promoting its binding to a chemokine coreceptor, such as CCR5 or CXCR4, on host cells. A conformational change in gp41, another glycoprotein expressed on the HIV envelope, exposes a fusion peptide, which inserts into the T cell membrane, allowing fusion of viral and cell membranes and subsequent infection of the host cell. Thus, CD4, CCR5, and CXCR4 are host proteins that are directly involved in mediating HIV entry into susceptible T cells, macro-phages, and dendritic cells. Env, the HIV envelope glycoprotein that includes gp120 and gp41, is also directly involved in mediating HIV entry into host cells. In contrast, MHC class I molecules do not have a direct role in this process.
16.A 36-year-old man with a history of a positive anti-HIV antibody test comes to the clinic with fever, sore throat, nonproductive cough, and weight loss. The patient has a high serum viral load, quantified by reverse transcriptase polymerase chain reaction (RT-PCR). This patient is LEAST likely to suffer from which of the following?
A.Kaposi’s sarcoma
B.Pneumocystis jiroveci pneumonia
C.Encephalopathy
D.Cachexia
E.T cell lymphoma
ANS: E
Based on this patient’s severe clinical presentation, his human immunodeficiency virus (HIV) disease has already progressed to AIDS. This final, almost invariably lethal phase is characterized by essentially complete destruction of peripheral lymphoid tissue, such that the blood CD4+ T cell count drops below 200 cells/mm3 and HIV viremia increases dramatically as viral replication proceeds unchecked. As a result, patients with AIDS often suffer from (1) multiple opportunistic infections, including Pneumocystis jiroveci pneumonia and oral candidiasis; (2) tumors such as Kaposi’s sarcoma; (3) central nervous system degeneration (encephalopathy); (4) kidney failure (nephropathy); and (5) generalized wasting (cachexia). Although AIDS patients are at risk for B cell lymphomas, T cell lymphomas are not a typical complication. HIV does not act as an oncovirus.
17.A 36-year-old man with a history of a positive anti-HIV antibody test comes to the clinic with fever, sore throat, nonproductive cough, and weight loss. This patient has had a partner for 8 years with whom he has frequently engaged in unprotected sexual intercourse. The partner is a healthy 29-year-old man who is HIV negative. The partner’s relative “resistance” to HIV infection may be due to a loss-of-function mutation in which of the following proteins?
A.CD4
B.CD8
C.CCR5
D.Tumor necrosis factor (TNF)
E.NF-B
ANS: C
CCR5 is one of the coreceptors required for human immunodeficiency virus (HIV) infection in vivo. Individuals who do not express the normal CCR5 chemokine receptor because of genetic mutations are resistant to HIV infection despite repeated exposure. This finding underscores the importance of CCR5 as a cofactor in mediating HIV viral fusion with the host cell membrane. Interestingly, many HIV-infected individuals transition from the production of virus that uses CCR5 (macrophage-tropic virus), early in the disease to virus that binds to CXCR4, another chemokine receptor (T cell line tropic virus) late in the disease. A loss-of-function mutation in CD4 would also “protect” an individual from HIV infection, but because this individual would also lack CD4+ T cells, he would not present as a healthy 29-year-old man.