Formative Quiz Review 3

Question 1

Which of the following is the MOST LIKELY outcome of using abatacept (CTLA-4-Ig) in the treatment of rheumatoid arthritis?

Activate regulatory T cells

Induce T cell anergy

Induce Th2 differentiation

Inhibit B cell activation

Inhibit mast cell activation

Answer 1

Induce T cell anergy

A. Incorrect. Abatacept blocks stimulation through CD28 by binding B7. Blocking CD28 does not activate regulatory T cells.
B. Correct. Blocking CD28 function will result in stimulation through the TCR alone, a process that induces anergy.
C. Incorrect. Without co-stimulation, T cells will not become activated or differentiate into any subset.
D. Incorrect. While B7 is expressed on B cells, stimulating B7 with CTLA-4-Ig does not have a known outcome.
E. Incorrect. Neither CD28 nor B7 are expressed on mast cells.

Question 2

A liver transplant patient received three daily doses of anti-thymoglobulin (ATG) prior to surgery to deplete his T cells and minimize the risk of graft rejection. After surgery, the patient receives additional ATG injections daily for five days. On the fifth day postsurgery, the patient develops a high fever (40°C), severe hypotension, and purpura. Which of the following mediators most likely is responsible for all of these symptoms?

Granzyme B

IFNγ

IgE

Immune complexes

Mannose-binding lectin

Answer 2

Immune complexes

A. Incorrect. Granzyme B is a component of the cell-mediated immune response and would not cause fever, hypotension or purpura.
B. Incorrect. IFNγ is required for the cell-mediated immune response. While it might induce fever and hypotension (through NO), it is not known to cause purpura.
C. Incorrect. IgE is a component of the Type I hypersensitivity response. While this could occur in this scenario, it is unlikely and IgE does not induce purpura.
D. Correct. This is a classic Type III hypersensitivity response characterized by an accumulation of immune complexes, the activation of complement and the release of peptides mediators that explain all of these symptoms.
E. Incorrect. While complement is an important component of Type III hypersensitivity, the classical pathway combined with the amplification loop of the alternative pathway is used, not the lectin pathway.

Question 3

A 27-year-old woman was jogging on her treadmill, as she did every day, but noticed her pulse reached 160 beats per minute within 60 seconds on the track. She quickly exhausted herself. She sought advice from her physician, who found out she was also losing weight. The physician also noticed a large, bulging thyroid gland in her neck. The gland was later removed, and a representative section is shown in the accompanying photomicrograph. Which one of the following is the best diagnosis?

Follicular carcinoma

Graves’ disease

Hashimoto thyroiditis

Multinodular goiter

Papillary carcinoma

Thyroid adenoma

Answer 3

Graves’s disease causes hyperthyroidism, and histologically shows infolding of the follicular epithelium into papillary structures (“P”). Scalloping (“S”) of the colloid, from resorption, is also prominent. See also Fig. 24-13 and surrounding text, Robbins, Cotran, and Kumar. There is also an available Aperio virtual slide, which has similar histology.

Question 4

A 36-year-old woman noticed a lump in her neck. When seen by her physician, she also noted that she had been fatigued lately. He palpated a nodular thyroid that was somewhat tender. Because of the cosmetic defect that the patient felt, the thyroid was removed. A representative section is shown in the accompanying photomicrograph. Which one of the following is the best diagnosis?

Follicular carcinoma

Graves’ disease

Hashimoto thyroiditis

Multinodular goiter

Papillary carcinoma

Thyroid adenoma

Answer 4

Hashimoto thyroiditis is a common cause of hypothyroidism and goitrous enlargement of the thyroid. Rarely, it can cause hyperthyroidism. The histological appearance is characteristic, with lymphoid follicles (“F”) commonly seen, along with atrophy of thyroid follicles. See also Fig. 24.11 and surrounding text, Robbins, Cotran, and Kumar. There is also an available Aperio virtual slide, which has similar histology.

Question 5

A gaping wound is made in the skin of a rabbit. The wound is large in surface area, and no attempt is made to surgically appose the edges, although bleeding was controlled. After 6 weeks of observation, which of the following would be the expected result with proper nutrition?

Healing by primary intention

Healing by resolution

Healing by resolution, with minimal scarring

Healing by secondary intention

Ulceration (the wound would not heal)

Answer 5

Healing by secondary intention

Question 6

The tissue biopsy shown in the accompanying photomicrograph was taken from deep within a diabetic foot ulcer. Which one of the following is the best overall description of the cellular changes seen in the photomicrograph?

Acute inflammation

Chronic inflammation

Granulation tissue

Granulomatous inflammation

Mature scar

Answer 6

Granulation tissue

Question 7

A cancer patient becomes extremely leukopenic, thrombocytopenic, and anemic following her latest chemotherapy treatment. To alleviate the anemia, the oncologist decides to give the patient a unit of packed red blood cells, which is later found to be ABO mismatched. Within an hour, the patient develops chills and a fever. Which of the following mediators is most likely responsible for this reaction?

C3

IFN-g

IgE

IL-4

IL-5

Answer 7

A. Correct
B. The transfusion reaction is a classic type II hypersensitivity. IFN promotes Th1 responses that are involved in type IV reactions. Also note the time frame of the reaction. It occurred within an hour. This is much more consistent with a type II hypersensitivity than a type IV reaction which can take days.
C. IgE is typically not required for type II hypersensitivities.
D. This patient had preexisting antibodies against the mismatched RBCs. Cytokines are not required for this reaction.
E. This patient had preexisting antibodies against the mismatched RBCs. Cytokines are not required for this reaction.

Question 8

A experimental strategy for the treatment of certain autoimmune diseases is to administer a soluble protein that binds B7 family members. Which of the following is the intended result of this therapy?

Promote the differentiation of Th1 cells

Promote NKT cell activation

Suppress MHC expression

Suppress T cell activation

Suppress NK cell-mediated killing

Answer 8

A. Binding B7 family proteins will block stimulation through CD28. Without CD28, T cells canot become activated and differentiate into Th1 cells.
B. Blocking CD28 will not promote activation of NKT cells.
C. B7 proteins are unrelated to MHC expression.
D. Correct Suppress T cell activation
E. NK cells do not bind B7

Question 9

Family members of a patient who needs a kidney transplant are being tissue typed to identify a suitable organ donor. Which of the following tests measures whether the patient’s lymphocytes are activated by cells from any of the prospective donors?

Mixed lymphocyte reaction

Major crossmatch

Minor crossmatch

HLA typing

Delayed hypersensitivity skin testing

Answer 9

Mixed lymphocyte reaction

Crossmatches are serological assays that measure antibody to tissue antigens. HLA typing will determine the HLA type, but does not measure lymphocyte responses in vitro, and skin testing is not used in transplantation to select donor and recipient pairs.

Question 10

At age 3 months, a girl was diagnosed as suffering from aplastic anemia. After receiving a hematopoietic stem cell transplant from her mother, she was treated with cyclophosphamide. Her course was unremarkable until three weeks post-transplantation when the patient developed jaundice, hepatosplenamegaly, diarrhea and a patchy red rash over her anterior neck and scalp. Which of the following most likely caused this post-transplant disease, which was successfully treated with cyclosporine A?

An IgE-mediated drug reaction to cyclosphosphamide

Graft-verus-host disease

Autoantibody production leading to immune complex deposition

Rejection of the donor stem cells

An opportunistic virus infection

Answer 10

Graft-verus-host disease

These signs are diagnostic of GvHD as is a positive response to immunosuppressive therapy.

Question 11

A 72-year-old man complains of bilateral swelling and pain in the joints of his hands and feet. Several of his proximal phalangeal joints are noticeably deformed. A radiograph of the right hand shows a narrowing of the joint spaces in three of his digits. Which of the following additional findings would support a diagnosis of rheumatoid arthritis in this patient?

A decreased erythrocyte sedimentation rate

Serum antibodies to double strand DNA

Antibodies to IgG in the serum

A positive response to antibiotics

Autoantibody to the TSH receptor

Answer 11

Antibodies to IgG in the serum

Rheumatoid factor (anti-IgG) is often present in a variety of rheumatological diseases. However, it is more diagnostic in this case, because the other choices are fairly specific for autoimmune diseases other than rheumatoid arthritis (anti-dsDNA = lupus; anti-TSH receptor = Grave’s disease).

Question 12

For which of the following conditions is hematopoietic stem cell transplantation an effective and routine therapy?

DiGeorge Syndrome

HIV/AIDS

SCID

C3 deficiency

Myasthenia gravis

Answer 12

Severe congenital T cell immune deficiencies are among the conditions treated with stem cell transplantation. SCID is severe combined immune deficiency and requires a source of lymphocyte progenitor cells to effect replacement of the lymphocyte pool (rescue).

Question 13

In which of the following conditions does an abnormal response to microbial flora appear to lead to a chronic inflammatory disease?

Graft-versus-host disease

Atopic asthma

Crohn’s disease

Hereditary angioedema

Myasthenia gravis

Answer 13

The chronic inflammatory bowel disease known as Crohn’s disease results from dysreguation of the immune system in the gastrointestinal tissues. T cells committed to microbial flora antigens appear to become excessively activated and produce proinflammatory mediators, including TNF. This cytokine damages epithelial cells lining the gut wall and ulcers can form. Simply giving these patients antibodies to TNF provides many of these patients a significant degree of relief.

Question 14

Which of the following is an example of an immunological cross-reaction that is commonly seen in clinical medicine?

The transfer of maternal IgG across the placenta

The reaction of isohemagglutinins with microbial carbohydrate antigens

The binding of mouse IgG to the human Fc receptor

The binding of complement to IgM

The translocation of IgA across the intestinal epithelium

Answer 14

The reaction of isohemagglutinins with microbial carbohydrate antigens

Crossreactions involve the binding of two different antigens by a given antibody. This often occurs when the two antigens share an epitope. A common example is the crossreaction between normal flora carbohydrate moieties and the ABO blood group antigens, which are also polysaccharide in nature.

Question 15

For which of the following conditions would methotrexate be an inappropriate treatment?

Renal allograft rejection

Systemic lupus erythematosus

Rhematoid arthritis

Graft-versus-host disease

CMV infection

Answer 15

An immunosuppressive drug, such as methrotrexate, would be appropriate for treating certain forms of graft rejection, lupus, RA and even GvH. However, one would never treat a patient with a viral infection with such a drug. Inhibition of the immune system (immunosuppression) would place this patient at risk for developing a complicated, disseminated virus infection and perhaps other opportunistic infections.

Question 16

A 35-year-old woman presents with fatigue and anemia and her history suggests an autoimmune disease. A Coombs test is positive. Which of the following laboratory test results would also be expected for this patient?

A protein spike on serum protein electrophoresis

Decreased C1, C2 and C4 levels

Elevated serum tryptase

Skin test anergy when tested with fungal and bacterial antigens

Unresponsiveness in the mixed lymphocyte culture

Answer 16

Decreased C1, C2 and C4 levels

Anemia and a positive Coombs test suggest antibodies to erythrocyte antigens. If large amounts of antigen-antibody complexes were to form that involved hemolytic isotypes of antibodies (IgM or IgG), then classical pathway complement components would become depleted.

Question 17

A 35-year-old woman is experiencing fatigue and heat intolerance and shows elevated levels of circulating thyroid hormone. Her serum also contains antibody to the TSH receptor. What is the likely diagnosis of this disease?

Systemic lupus erythematosus

Myasthenia gravis

Multiple sclerosis

Goodpasture syndrome

Grave’s disease

Answer 17

Grave’s disease

Grave’s disease is a condition resulting from stimulation of the thyroid with agonistic antibody to the TSH receptor. In other words, the antibody acts like TSH and causes hyperthyroidism.

Question 18

Which one of the following drugs is used in organ transplantation and blocks transcriptional activation of cytokine genes in T cells as its primary mode of action?

Cyclophosphamide

Epinephrine

Cyclosporine

Cyclohexamide

Dexamethasone

Answer 18

Cyclosporine

Drugs of the cyclosporine family bind cyclophilin and thereby inhibit calcineurin, a phosphatase that dephosphorylates NF-AT. Dephosphorylated NF-AT is a transcription factor that transactivates a number of cytokine genes in T cells. In the presence of the drug, NF-AT is phosphorylated (inactive).

Question 19

A 52-year-old woman received an allogeneic renal transplant two months ago. She was progressing satisfactorily on immunosuppressive drugs and the dosage of the drugs had been decreased recently. Within the last week, she began to experience fever, a tender, painful and swollen kidney and a decline in renal function (decreased urinary output, elevated BUN). Which of the following is most likely responsible for her declining clinical course over the past week?

An opportunistic viral infection

Immune complex deposition in the kidney

Graft-versus-host disease

Acute allograft rejection

Diabetic nephropathy

Answer 19

Acute allograft rejection

Two months after renal transplant with a kidney from an allogeneic donor, one might expect graft rejection to still occur, especially after decreasing immunosuppressive therapy. Fever, tender organ and decline in organ function are all consistent with graft rejection. GvH rarely occurs with renal transplants and there is no reason to suspect diabetic nephropathy at this early time.

Question 20

A 32-year-old woman with systemic lupus erythematosus and mild renal insufficiency has decreased serum C3 and C4 components of complement in her serum. What is the best hypothesis for the pathogenesis of her hypocomplementemia?

genetic decrease

immune complex formation

loss of complement in urine

poor liver function

sequestration of complement in the spleen

Answer 20

immune complex formation

Lupus classically has numerous auto-antibodies, resulting in the formation of macromolecular antigen-antibody complexes, which deposit in the glomeruli and in small vessels, particularly those of the skin. There, they fix complement and damage tissue.

Question 21

The blood lymphocytes of a 6-month-old child with recurrent, complicated viral and fungal infections do not respond normally to IL-2, IL-4 or IL-7 in vitro. The patient has a single gene mutation that explains all of these findings. Which one of the following is the most appropriate therapy for the immune deficiency of this patient?

Recombinant IL-2

Recombinant IL-3

Hematopoietic Stem cell transplantation

Thymus transplantation

Gene therapy to correct a defective CD3ζ chain gene

Answer 21

Hematopoietic Stem cell transplantation

A. The patient does not respond to IL-2, so there is little rationale for providing this as a treatment.
B. IL-3 might correct a defect in lymphocyte growth, especially from progenitor cells, but there is no evidence the patient lacks lymphocytes. Indeed, the question states that the patient has lymphocytes that simply do not respond.
C. Correct. The description suggests that this patient lacks the ability to respond to three different, but related cytokines. What they share is common are their receptors, each of which has the common γ chain. Thus, this patient probably has SCID secondary to IL-2Rγ chain deficiency. The preferred therapy is stem cell replacement.
D. There is no indication here that the patient has defective thymic function. Indeed, he has sufficient blood lymphocytes to test.
E. Such a deficiency does exist and would give rise to the lack of T cells and recurrent viral and fungal infections. However, the absence of TCR signaling through CD3 should not impair cytokine receptor signaling by IL-2, IL-4 and IL-7. These are independent signaling pathways.

Question 22

Johnny is an 8-month-old child with recurrent fungal and viral infections. His blood lymphocytes can bind IL-2 or IL-4 in vitro. It has been determined that his parents both carry a genetic mutation in their ZAP-70 genes that would explain Johnny’s disease. In addition to antimicrobial agents to treat his infections, what therapy would you recommend for Johnny?

Thymus transplantation

IVIG and all of the pediatric vaccines

Recombinant IL-2 and recombinant IL-4

Hematopoietic Stem cell transplantation

Besides antimicrobials, there are no effective therapies for this patient.

Answer 22

Hematopoietic Stem cell transplantation

A. There is no evidence here that Johnny’s thymus is defective and the defect in ZAP-70 can explain his presentation.
B. IVIG would not be useful at this age because he his still depending on maternal antibodies. It also would not correct his apparent defect in cellular immunity. Until this is corrected, some of the pediatric vaccines might not be effective.
C. While exogenous IL-2 and IL-4 might seem a logical choice, their short half lives would limit their effectiveness in correcting this immune deficiency.
D. Correct. The only correction to this cellular immune defect is stem cell replacement. One would want to verify that the patient’s T cells also lack functional ZAP-70.
E. There is an effective therapy for this apparent defect in cellular immunity.

Question 23

A patient with systemic lupus erythematosus is experiencing significant symptoms, including edema and skin rash, and has shown a recent increase in serum BUN and creatinine. A biopsy of her kidney reveals deposition of IgG at the glomerular basement membrane. If you were to follow her serum complement levels over time, which one of the following findings would be MOST CONSISTENT with a worsening clinical course?

A decline in C9 levels

A decline in C3 and C4 levels

An increase in Factor P levels

An increase in C1 Inh levels

A decline in C7 levels

Answer 23

A decline in C3 and C4 levels

A. This patient has evidence of immune complex deposition in her kidney and would be expected to have circulating IgG immune complexes as well. Such immune complexes can cause complement activation via the classical pathway leading to a depression in C1, C2, C4 and C3 levels. C9 levels would not be expected to be depleted, because complement activation is in fluid phase and does not proceed to the terminal components.
B. Correct. This patient has evidence of immune complex deposition in her kidney and would be expected to have circulating IgG immune complexes as well. Such immune complexes can cause complement activation via the classical pathway leading to a depression in serum C1, C2, C4 and C3 levels.
C. There is no reason to expect compensatory increases in Factor P because this patient’s complement activation does not involve the alternative pathway. As a rule of thumb, lupus patients will show acute exacerbations of disease characterized by reductions in the levels of their early classical pathway components due to the activation of complement and the clearance of these peptides by antigen-antibody complexes.
D. There is no reason to expect compensatory increases in Factor P because this patient’s complement activation does not involve the alternative pathway. As a rule of thumb, lupus patients will show acute exacerbations of disease characterized by reductions in the levels of their early classical pathway components due to the activation of complement and the clearance of these peptides by antigen-antibody complexes.
E. Following C7 levels does not provide useful information. This patient has evidence of immune complex deposition in her kidney and would be expected to have circulating IgG immune complexes as well. Such immune complexes can cause complement activation via the classical pathway leading to a depression in serum C1, C2, C4 and C3 levels.

Question 24

Two months following allogeneic stem cell transplantation for the treatment of acute lymphoblastic leukemia, a patient presented with diarrhea and a blistering, erythematous appearance to the skin of his anterior neck and back. Serum chemistry revealed elevated liver enzymes, and the liver and cervical lymph nodes appeared enlarged on physical exam. What disease or disease mechanism is MOST LIKELY causing this clinical picture?

Rejection of the transplant

Autoantibody production against the patient’s lymphocytes

Deposition of immune complexes in the skin and liver

Graft-versus-host disease

A reaction to his immunosuppressive drugs

Answer 24

Graft-versus-host disease

A. Rejection of transplanted stem cells would not produce this constellation of signs and laboratory findings.
B. While autoantibody production, even leading to autoimmune anemia and thrombocytopenia, is not uncommon during the post-transplant period, the symptoms of skin rash and diarrhea do not fit this pathogenic scenario.
C. The timing, distribution and nature of lesions does not exactly fit immune complex deposition. Blistering rashes are not common in IC-mediated disease and localization to the anterior surface of the neck is not typical.
**D. Correct. These are classical symptoms of GvH disease: anterior suface rash that takes on a sunburn-like appearance, liver and intestinal involvement and lymphadenopathy all typically appear several weeks following engraftment. The tissue distribution of GvH parallels the distribution of allogeneic class II MHC in the recipient. Class II is a potent stimulus for the activation of donor-derived allogeneic T cells.**
E. There is no reason to connect these particular signs and laboratory findings with such a reaction.

Question 25

If you were to purify the cells from human bone marrow that expressed this cell surface marker, you would have a population greatly enriched in hematopoietic stem cells. What is the cell surface marker?

CD1

CD2

CD18

CD34

CD40

Answer 25

CD34

A. CD1 is a widely-expressed molecule that presents glycolipid antigens to NKT cells.
B. CD2 is an adhesion molecule found on T cells and NK cells.
C. CD18 is a b2integrin chain that pairs with different a chains to form the adhesion molecule LFA-1 or the complement receptors CR3 and CR4.
D. Correct. Immunoselection (purification with antibodies) for CD34 bone marrow cells will yield hematopoietic stem cells. This is a routine means of purifying such cells prior to stem cell transplantation.
E. CD40 is a coreceptor expressed on B cells that binds CD154 on Th cells and signals B cell activation.

Question 26

Which one of the following laboratory tests is routinely used to measure T cell function?

Coombs test

ELISA

Mixed lymphocyte reaction

Complement fixation test

ANA test

Answer 26

Mixed lymphocyte reaction

A. The Coombs test is a test for autoantibodies, typically those causing hemolytic anemias or thrombocytopenias.
B. The ELISA is used clinically to measure low concentrations of antigens or antibodies in body fluids or extracts.
C. Correct. The mixed lymphocyte reaction (mixed lymphocyte culture) measures the response to T cells to allogeneic HLA antigens in vitro
D. Complement fixation is used to measure the presence of antigen, antibody or complement activation in a fluid sample (e.g., serum or plasma). It measures classical pathway activation.
E. The antinuclear antibody test detects serum autoantibodies against a variety of nuclear antigens.

Question 27

As a treatment for end-stage renal disease, xenotransplantation differs from allotransplantation in the nature of the acute rejection process. Which one of the following mechanisms is important in the acute rejection of renal xenografts in human patients?

Production of IgE antibodies

Activation of HLA class I-restricted CD8 cytotoxic T cells

Binding of anti-HLA antibodies to donor tissues

Activation of complement by natural antibodies

Attraction of eosinophils into the graft

Answer 27

Activation of complement by natural antibodies

A. The involvement of IgE antibodies in the rejection of xenografts has not been described.
B. While this would be an important mechanism in the rejection of HLA-mismatched allografts in human beings, HLA antigens are not expressed on the tissue of non-human species.
C. While this would be an important mechanism in the hyperacute rejection of HLA-mismatched allografts in human beings, HLA antigens are not expressed on the tissue of non-human species.
D. Correct. Antigens on xenografts are recognized by preformed natural human antibodies of the IgM class. These are capable of activating complement and elaborating chemotactic factors (e.g., C5a), anaphylatoxins (e.g., C3a) and opsonins (e.g., C3b) that recruit and activate blood neutrophils for cytotoxicity of the graft tissues
E. The cells initially recruited to the xenograft in large numbers are not eosinophils, but neutrophils.

Question 28

A 7-year-old girl complained of a 48-hour history of malaise, shivering, and difficulty eating and drinking due to painful swallowing. Her mother reported frequent colds accompanied by “bouts of tonsillitis” since early childhood. The patient was febrile (102.5ºF), and her pharynx, tonsils and buccal mucosa were inflamed. The tonsils were enlarged and studded with white exudative areas. A throat swab grew type A beta-haemolytic streptococci. After surgical removal of the palatine tonsils, the patient recovered uneventfully.

Which of the following was most likely observed upon histopathological examination of the tonsils of this patient?

Enlarged follicles

Epithelial hyperplasia

Lymphocytic leukemia

Obstruction of tonsillar crypts

Squamous cell carcinoma

Answer 28

Enlarged follicles

This patient had evidence of infections involving the tonsils. This would induce enlargement of the follicles, as the B cells proliferate.

Question 29

A 32-year-old woman from Sudan, who recently immigrated to the United States, presented to the emergency department with fever, abdominal pain, nausea and vomiting. Her medical history revealed that she had had multiple episodes of malaria. Computed tomography revealed splenomegaly and hepatomegaly, and laboratory tests revealed anemia and neutropenia.

Which area of the spleen is most likely responsible for the splenomegaly?

Cortico-medullary junction

Germinal centers

Periarterioloar lymphoid sheath

Red pulp

White pulp

Answer 29

Malaria infects red cells and the splenomegaly is caused by the infiltration of lymphocytes and neutrophils in the red pulp.

Question 30

A 35-year-old woman came to the hospital complaining of malaise, fever, diaphoresis, and a cough for several weeks. She was very thin and complained of having lost over 30 pounds in the last year without being on any special diet. The patient was given an intradermal injection of purified protein derivative of a microbe (tuberculin test) to confirm a presumptive diagnosis. Forty-eight hours later the injection site showed erythema and a 12-mm raised induration. This is a positive result and an example of which of the following reactions?

Arthus reaction

Atopic reaction

Complement-mediated reaction

Delayed-type hypersensitivity reaction

Wheal and flare reaction

Answer 30

Delayed-type hypersensitivity reaction

This question builds a patient history leading to the mechanism of the PPD test, which is a type IV reaction, also called a DTH response.

Question 31

A 30-year-old man presents with recurrent bacterial infections over the course of the past several years. Prior to these infections, the patient reports no significant medical history. Which of the following lab tests would be most useful for establishing a diagnosis of immune deficiency and why?

Flow cytometry for suspected defect in MHC class I expression

Flow cytometry for suspected defect in MHC class II expression

CBC with differential for suspected XLA

Flow cytometry for suspected B cell deficiency

Quantitative serum immunoglobulins for suspected common variable immune deficiency

Answer 31

Quantitative serum immunoglobulins for suspected common variable immune deficiency

Recurrent infections in someone in their 3rd decade of life raises the possibility of CVID and quantitative serum Igs is an appropriate test that will assist in the diagnosis.

Question 32

As blood flows into the spleen to carry antigens to splenic B cells, which of the following structures is the first to have detectable concentrations of antigen?

Follicle

Germinal center

Marginal zone

PALS

Red pulp

Answer 32

Marginal zone

Blood flows through the marginal zone where antigen is trapped by marginal zone macrophages. This would be the first place where antigen accumulates. Then, antigen would filter into other regions.

Question 33

T cell receptors binding allogeneic MHC is an example of which of the following processes?

Billingham’s postulates

Clonal selection

Cross-reaction

Hyperacute rejection

Opsonization

Answer 33

T cells are selected against autologous MHC, not allogeneic MHC. Any binding of T cells to allogeneic MHC is a cross-reaction.

Question 34

Which of the following events is MOST likely to place patients at risk for acute graft-versus-host disease?

Antibody binding

Complement activation

Macrophages activation

Myeloablative therapy

Th1 cell activation

Answer 34

Myeloablative therapy

Myeloablative therapy induces tissue damage and inflammation, which contributes to T cell activation. While Th1 cell activation is a component of aGvHD, the primary risk factor is the inflammation caused by myeloablative therapy.

Question 35

Which of the following is the primary cause of hypotension in the patient with sepsis in the Jarisch Herxheimer case?

Acute phase protein synthesis

Dehydration

Increased vascular permeability

Interleukin-8-mediate chemotaxis

Vasodilation

Answer 35

Vasodilation

Be sure to concept map sepsis. Explain each major clinical event to a molecular mechanism. Vasodilation would cause a drop in blood pressure to a greater extent that vascular permeability.

Question 36

A 54 year-old man underwent allogenic liver transplantation for primary biliary cirrhosis and his liver function is recovering as expected. In considering routine prophylactic therapy for the prevention of allograft rejection, which of the following molecules would be MOST APPROPRIATE to inhibit?

C5 convertase

Calcineurin

Cyclooxygenase

FcγRIIb

Phosphodiesterase

Answer 36

Calcineurin

A. Incorrect. Allograft rejection is mediated primarily through a Th1-dependent manner. Complement is problematic primarily in xenograft rejection, which was not used here.
B. Correct. Commonly used drugs for the prevention of allograft rejection are cyclosporine and tacrolimus, which block calcineurin activity.
C. Incorrect. Cyclooxygenase inhibitors are effective for the treatment of inflammatory conditions, such as arthritis.
D. Incorrect. FcγRIIb is bound by Rhogam, which prevents B cell activation.
E. Incorrect. Phosphodiesterase is the target for theophylline and is used in asthmatic patients.

Question 37

Which of the following would be true about a man with a blood type of O?

He has no antibodies to ABO antigens.

His cells would be agglutinated by serum from an A donor.

His cells would be agglutinated by serum from an AB donor.

His serum would agglutinate O cells.

His serum would agglutinate A cells.

Answer 37

His serum would agglutinate A cells.
A. Incorrect. O individuals have both anti-A and anti-B.|
B. Incorrect. A donors contain anti-B, which is not present on O cells.
C. Incorrect. AB donors do not contain anti-ABO.
D. Incorrect. O individuals do not contain antibodies that recognize O cells (self).
E. Correct. O individuals contain anti-A, which would agglutinate A cells

Question 38

An otherwise healthy adult male presents with blurred vision and right leg numbness with increasing duration and intensity. He complains of weakness in his arms that prevents him from lifting heavy objects. MRI shows several small lesions in the white matter of his brain and his cerebral spinal fluid contains oligoclonal bands. Which of the following allergic diseases utilizes a similar pathogenic mechanism of tissue damage seen in this patient?

Allergic contact dermatitis to poison ivy

Atopic asthma

Bee sting anaphylaxis

Hereditary angioedema

Lupus nephritis

Answer 38

Allergic contact dermatitis to poison ivy

A. Correct. This patient has clinical features typical of multiple sclerosis, which is mediated by activated CD4+ T cells and macrophages. Th1 cells and activated macrophages are also central to the development of poison ivy rash.
B. Incorrect. Allergic anaphylaxis is due to a type I mechanism involving IgE antibodies and mast cells.
C. Incorrect. Atopic allergic asthma is initiated by IgE antibodies and mast cells, but continues as a chronic disease to involve eosinophils, airway damage and remodeling and lung hyper-responsiveness.
D. Incorrect. HAE is an immune deficiency involving an absence of C1 Inh and uncontrolled episodic complement activation.
E. Incorrect. Lupus nephritis is due to immune complex deposition, a type III reaction.

Question 39

A 75-year-old woman presents with a fracture of her hip following a fall in her home. Imaging indicates several osteolytic bone lesions and CBC shows anemia, leukopenia and thrombocytopenia. She has elevated total serum protein, but decreased serum albumin. Her serum IgG levels are markedly elevated and her urine contains monoclonal Ig light chains. What is the likely cause of her bone lesions?

Activated T cells in the bone

Dietary calcium deficiency

Malignant bone marrow plasma cells

Metastic breast cancer in the bone

Osteoporosis

Answer 39

Malignant bone marrow plasma cells

A. Incorrect. Several findings are not consistent with this mechanism: elevated IgG, anemia, leukopenia and elevated total serum protein.
B. Incorrect. Calcium deficiency would affect bone formation and generalized bone density, but would not present as well-delineated porous osteolytic lesions.
C. Correct. This is the presentation of multiple myeloma, which includes overgrowth of the bone marrow by malignant plasma cells. The malignant cells produce cytokines, which activate osteoclasts in their immediate vicinity causing a “porous” round lesion of decreased bone density.
D. Incorrect. While consistent with some features of this case, including the production of focal lesions in the bone and bone fractures, metastatic breast cancer would not give rise to an M protein (monoclonal Ig).
E. Incorrect. Osteoporosis does not present as focal round porous bone lesions, although it can result in loss of bone density and fractures.

Question 40

A 17-year-old male presents with a history of sore throat, fever and myalgia of 4 days duration. Physical exam shows tachypnea, a fever of 39oC, enlarged cervical nodes and erythematous pharynx. His CBC shows 12,000 WBC/ml with 25% granulocytes, 30% lymphocytes, 20% atypical lymphocytes and 10% monocytes. Flow cytometry shows an elevated CD8 T cell percentage with all other subsets within normal ranges. The rapid step test on a throat swab was negative, but the Monospot test was positive. What is the identity of the atypical blood lymphocytes in this patient?

Activated macrophages

Circulating malignant B cells

Cytotoxic T cells

T cell leukemia cells

Virus-infected B cells

Answer 40

. Incorrect. Activated macrophages do not typically circulate and are not found to do so in infectious mononucleosis.
B. Incorrect. While circulating malignant lymphocytes may also be classified as “atypical,” the other findings (sore throat, erythematous pharynx, positive Monospot test) all point to EBV infection.
C. Correct. The atypical lymphocytes of infectious mononucleosis are CD8+ cytotoxic T cells that are specific for EBV antigens being presented on infected B cells.
D. Incorrect. There is no reason to postulate a malignancy in this case. Most of the clinical data are consistent with an infection and the positive Monospot test confirms EBV infection.
E. Incorrect. While there are EBV-infected B cells in this disease, they are not the atypical lymphocytes seen in the bloodstream. The latter are all CD8-positive and contain cytosolic granules typical of cytotoxic T cells.

Question 41

A 19-year-old college football player presents to the university student health clinic with symptoms of a sexually-transmitted disease, which is diagnosed as gonorrhea. He is prescribed antibiotics (ceftriaxone), which lessens primary symptoms, but four days later he develops a fever of 39.8oC and unilateral left knee pain, redness and swelling. A synovial fluid sample reveals numerous infiltrating neutrophils and gram-negative cocci, but no crystals. CBC demonstrates leukocytosis with 10% bands. Which of the following is the MOST IMPORTANT immune mediator of his arthritis?

Activated mast cells and histamine

Antibodies to the gonococcus bacterium

Autoantibodies

Macrophages activated by microbial patterns

T cells activated by self antigens in the joint

Answer 41

Macrophages activated by microbial patterns

A. Incorrect. Mast cells are not a major pathogenic mediator of arthritis and would not be activated by infection.
B. Incorrect. Four days is a very short time for an antibody to develop to microbial antigens in sufficient quantities to produce immune complex-mediated arthritis.
C. Incorrect. Autoantibodies as mediators of arthritis more often produce a different pattern of disease onset. Rheumatoid arthritis, for example, generally develops slowly over time with the small joints of the hands and feet first being affected. The disease is also typically bilateral in its distribution.
D. Correct. The proximal association of unilateral acute-onset arthritis in this patient, his risk factor of potential prior knee injuries, the finding of bacteria and leukocytes in the joint and the clinical laboratory findings all point to an infectious process – septic arthritis.
E. Incorrect. This would be more the mechanism of arthritis in an autoimmune disease, such as rheumatoid arthritis.

Question 42

A kidney from a deceased donor is made available to a renal transplant program, which has several potential recipients on its waiting list. Assuming all cross-matches are negative and the ABO types are appropriately matched for the four recipients listed below, which is the preferred recipient of the donor kidney based on the following HLA typing data?

Recipient 1

Recipient 2

Recipient 3

Recipient 4

Recipient 1 and 2 are equally preferred.

Answer 42

A. Incorrect. Recipient 1 recognizes two allelic products (HLA antigens) at the A locus, one at the B locus, one at the C locus and one at the DR locus. This is a terrible match.
B. Correct. Of the choices available, this is the best. Recipient 2 recognizes only one antigen at the A locus. That is a tolerable degree of incompatibility and should be manageable in the post-transplant period.
C. Incorrect. Recipient 3 recognizes on antigen coded by A, two coded by B, and one coded by C. While no class II disparities exist, this is a lot of class I antigenic differences to manage.
D. Incorrect. Recipient 4 recognizes one antigen at A, two antigens at B and one antigen at DR. Because both class I and class II differences exist, the recipient will mount a vigorous rejection response.
E. Incorrect for the reasons stated above.

Question 43

A 1 year-old boy presents to an urgent care clinic with a fever (39.5°C) and coughing. A chest X-ray revealed several large cotton-like structures in the lungs with the appearance of granulomas. The child’s WBC was 17,000 (normal 5,000-14,500 cells per μl) with 65% neutrophils (normal 37-71%). A nitroblue tetrazolium assay was negative. Which of the following proteins is most likely lacking from this patient?

Arginine synthase

G-CSF

IL-12

LFA-1

NADPH oxidase

Answer 43

ANS: E
This patient has a classic presentation of chronic granulomatous disease, characterized by a defect in the respiratory burst leading to the production of reactive oxygen intermediates, an effector mechanism of neutrophils. The molecules most typically mutated in CGD patients are those part that comprise the NAPDH oxidase complex.

Question 44

A two year old-girl presents to the emergency department with a fever (40°C) and cough. This patient has had an extensive history of chronic sinusitis, otitis media, and upper respiratory infections. Her most recent CT scan was taken two months ago and revealed bronchiectasis, evidence of chronic inflammation in the bronchi. Early in life, the infections were primarily viral in nature, but progressed to bacterial and viral later. Analysis of the patient’s lymphocytes demonstrated normal numbers of B cells and CD4+ T cells, but few CD8+ T cells. Which of the following proteins in most likely deficient in this patient?

Btk

CIITA

γc

RAG-1

TAP

Answer 44

TAP

This patient lacks CD8+ T cells, but other lymphocyte subsets are normal. This indicates that there is a defect in this lineage. The protein required for this lineage is TAP, which is required for MHC class I antigen presentation. CIITA is required for MHC class II, which appears normal in this patient. Btk affects B cells. RAG-1 and γc affect B, CD4+, and CD8+ T cells. Another clue that this is a CD8+ T cell-driven process is that early in life, the problematic pathogens were viral in nature. These chronic infections led to chronic inflammation and the inability of the lungs to clear mucus and pathogens. This led to the bacterial infections after the tissue damage was established.

Question 45

A 75-year-old woman presents to her physician for a follow-up appointment for the pain in her fingers on both hands. She had been previously diagnosed with rheumatoid arthritis and has been prescribed anti-inflammatory medications and several disease-modifying anti-rheumatic drugs, all of which relieved the pain temporarily, but today the patient reports worse pain than ever. Blockade of which of the following cytokines would most likely provide symptomatic relief for this patient?

IFNγ

IL-1

IL-2

TNFα

TGFβ

Answer 45

TNFα

ANS: D
TNFα inhibitors are commonly used for rheumatoid arthritis. While IFNγ
and IL-2 can also promote the T cell responses associated with rheumatoid arthritis and blockade of these may provide some relief, the most damage-associated cytokine is TNFα
produced by macrophages.

Question 46

A 43-year-old man with metastatic melanoma returns to his oncologist with an article he read on a news website regarding immunotherapy. He inquires as to whether this form of therapy could be used for his disease. Inhibition of which of the following molecules would be most likely to extend this patient’s lifespan?

CD28

CD40

CTLA-4

IL-2

TNFα

Answer 46

ANS: C
CTLA-4 is an inhibitory co-receptor found on T cells. Inhibition of this receptor allows for increased T cell activity and destruction of tumors. Inhibition of any of the other molecules would block T cell activation, allowing tumor growth.

Question 47

A 23-year-old woman ruptured her spleen in an automobile accident. After splenectomy and recovery from the surgery, it is your responsibility to advise the patient as to an appropriate vaccine schedule. You consider the types of vaccines available and the pathogens most likely to cause morbidity and mortality in this patient. To generate an effective immune response, which of the following cell types would be most important to recruit into the immune response against the vaccine?

CTL

DC

Tfh

Th1

NK

Answer 47

ANS: C
A splenectomized patient is at risk for life-threatening infections by encapsulated organisms. The types of vaccines available are polysaccharide vaccines or conjugated vaccines. It is critical to generate an optimal IgG immune response, which requires germinal center formation and follicular helper T (Tfh) cells. Keep in mind that, in this context, B cells are the primary antigen-presenting cells.

Question 48

A 24 year-old man presents to his physician with a fever (39.5°C) and productive cough. The patient has had multiple hospitalizations over his lifetime for severe infections that required intravenous antibiotics. Genome sequencing revealed a functional mutation in the gene encoding activation-induced cytidine deaminase. Which of the following Ig levels is most consistent with the disease?

Answer 48

ANS: E
A mutation in AICD leads to hyper-IgM syndrome, which is characterized by elevated IgM and reduced (not absent) IgG and IgA. Other diseases represented by these lab results include IgA deficiency, IgG deficiency, IgM deficiency, and general hypogammaglobulinemia.

Question 49

A genetic mutation in the gene encoding for activation-induced cytidine deaminase leads to what disease?

Answer 49

hyper-IgM syndrome

This genetic mutation leads to an inability for class switching in B cells

Question 50

A 23-year-old medical student presents to his primary care physician complaining that his sinuses and his eyes frequently are red and irritated. The symptoms prevent the student from adequately preparing for his exam. The student has tried antihistamines, topical steroids, and “allergy shots”, but nothing seems to relieve the symptoms. Inhibiting which of the following molecules would most likely provide symptomatic relief with the fewest adverse effects?

IL-1 receptor

IL-2 receptor

IL-12 receptor

IL-13 receptor

IL-17 receptor

Answer 50

ANS: D
The symptoms resemble a type I hypersensitivity, which is mediated by IgE. For IgE to be generated, patients require a Th2-mediated immune response and the cytokines required are IL-2, IL-4, IL-5, and IL-13. While blocking IL-2 could be effective, the immunosuppression resulting from its blockade would be profound and disproportionate to the symptoms described. However, blockade of IL-13 would only inhibit the Th2 pathway, leaving the patient susceptible to infection by a limited number of pathogens which are not problematic in developed countries.

Question 51

You are an infectious disease specialist who encounters a series of patients infected with an emerging pathogen that was recently discovered. Your patients typically present with high fevers and are often dehydrated because of the severe diarrhea. While the exact nature of the pathogen remains unclear, it is a species of bacteria. All of the patients have been infected after swimming in contaminated waters, suggesting a fecal-oral route of transmission. Frustrated by the number of patients being infected with this pathogen, you decide to attempt to generate a vaccine. Which of the following vaccine strategies is most likely to be successful in these patients?

Capsular polysaccharides administered intramuscularly

DNA vaccine administered intramuscularly

Heat-killed bacteria administered intranasally

Live attenuated bacteria administered orally

Live pathogenic bacteria administered rectally

Answer 51

Live attenuated bacteria administered orally

The pathogen infects through mucosal surfaces of the gastrointestinal tract. Thus, the best way to block infection is to generate an immune response in the GI tract, or at least at mucosal surfaces in general. This eliminates IM administration. Intranasal administration of heat-killed bacteria might provide some protection, but not as effect as a vaccine administered orally or rectally (not a common route in the U.S.). Live pathogenic bacteria will cause infection, which will prevent future infections, but this would not be desired. Therefore, the best answer is live attenuated bacteria administered orally.

Question 52

A six-year-old boy presents to the clinic complaining that his ankles “itched really bad”. Physical exam revealed a linear series of erythematous vesicles and bullae. The boy’s mother indicated that they were hiking in the woods a couple days earlier. When asked whether the boy had previously had poison ivy, his mother said that the boy had previously found some in the yard the previous summer and prepared a bouquet of it for her. The mother was shocked that the plant did not seem to bother him at the time. Which of the following mediators is most directly responsible for the rash on the boy’s leg?

C3

Histamine

IL-3

IL-17

TNFα

Answer 52

TNFα

This is a type IV hypersensitivity in which Th1 cells and macrophages release TNFα, causing the symptoms displayed here.

Question 53

A 58-year-old leukemia patient received myelosuppressive chemotherapy. Two weeks later, the patient’s hemoglobin level dropped to 4 g/dL (normal: 12-16). The patient received a unit of packed RBCs and within a few minutes developed a fever and chills. An investigation into the event revealed that the patient was blood type A, but received AB blood. Which of the following antibody classes is most likely responsible for the reaction observed?

IgA

IgD

IgG

IgE

IgM

Answer 53

ANS: E
This is a transfusion reaction caused by mismatched blood. The ABO antigens are polysaccharides, which are T-independent antigens. The most likely antibody isotype is IgM.

Question 54

An eight-year-old sickle cell patient presents to the emergency department with a fever (40°C), low blood pressure (60/40), and high heart rate (125 bpm). The patient is started on fluids and intravenous antibiotics and his condition improves over the next two days. Deficiency in which of the following immune responses most likely contributed to the patient’s infection?

CD8* T cell activation

IgA production

IgM production

Macrophage activation

NK cell activation

Answer 54

ANS: C
Sickle cell patients have severely compromised spleens, making it difficult to generate T-independent immune responses against systemic infections with encapsulated organisms. T-independent immune responses primarily result in the generation of IgM

Question 55

At 48 years of age, a woman was diagnosed with breast cancer. After lumpectomy and radiation therapy, there was no evidence of disease. The patient is now 56 years old and is suffering from a recurrence of the original cancer. An analysis of her blood revealed the presence of tumor-specific memory CD8+ T cells. Which of the following proteins is MOST LIKELY being secreted by the tumor that blocks the activation of tumor-specific CD8+ T cells within the tumor?

C3

C-reactive protein (CRP)

IL-3

IL-12

TGFβ

Answer 55

TGFβ

A. Incorrect. Tumor cells do not typically secrete C3. If tumor cells produced C3, it may promote tumor lysis.
B. Incorrect. CRP is an acute phase protein that is produced in the liver.
C. Incorrect. IL-3 would promote mast cell growth, which would not block CD8+ T cell activity.
D. Incorrect. IL-12 would promote the Th1 response, which would destroy the tumor.
E. Correct. Tumor cells secrete TGFβ, which contributes to the immunosuppressive tumor microenvironment.