allergy and immunology board review corner: 2013 · allergy and immunology review corner: chapter 5...

Allergy and Immunology Board Review Corner: 2013

Table of Contents

Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti

January Chapter 5: Inflammation Chapter 6: B Lymphocytes and Immunoglobulins

February Chapter 7: T Lymphocytes and Cell-Mediated Immunity Chapter 8: The Mucosal Immune System in Health and Disease

March Chapter 9: Cytokines, Chemokines, and the Immune System Chapter 10: Immunogenetics

April Chapter 11: Advanced in Clinical Immunomodulation Chapter 12: Immunity to Bacteria

May Chapter 13: Mechanisms of Immunity to Viral Disease Chapter 14: Mechanisms of Fungal Immunity

June Chapter 15: Clinical Immunology of Parasitic Diseases Chapter 16: Immune Deficiency Disorders

July Chapter 17: Mechanisms of Immunologic Injury Chapter 18: Allergic Diseases and Asthma

August Chapter 19: Tolerance, Autoimmunity, and Autoinflammation Chapter 20: Immune Responses to Cancer

September Chapter 21: Lymphoproliferative Disorders: Monoclonal Gammopathies and Neoplasms of the Immune System Chapter 22: Transplantation Immunity and Clinical Applications

Allergy and Immunology Review Corner: Chapter 5 of Immunology IV: Clinical

Applications in Health and Disease, by Joseph A. Bellanti, MD.

Chapter 5: Inflammation

Prepared by Meagan W. Shepherd, MD, Ohio State University

1. What are the main cytokines produced by Th17 cells?

A. IL-2, IFN-gamma, and TNF-beta

B. IL-10, IL-4, and TGF-beta

C. IL-4, IL-5, and IL-13

D. IL-17, IL-21, and IL-22

2. Which of the following is the most pro-inflammatory product formed during

complement activation?

A. C3b

B. C4a

C. C5a

D. C9

3. What is the ligand for VCAM-1 (CD106)?

A. LFA-1

B. VLA-4

C. Mac-1

D. ICAM-4

4. Which of the following is found in the dense granules of platelets and in the Weibel-

Palade bodies (granules) of endothelial cells?

A. P-selectin

B. E-selectin

C. L-selectin

D. LFA-1

5. Does expression of ICAM-2 on endothelial cells increase with stimulation?

A. Yes

B. No

C. Sometimes

D. Only if stimulated by LFA-1

6. Leukocyte Adhesion Deficiency Type I is due to a deficiency in which of the

following?

A. CD11

B. CD18

C. ICAM-1

D. ICAM-2

7. Chronic granulomatous disease (CGD) is caused by defect of which of the following?

A. CD18

B. Myeloperoxidase

C. NADPH oxidase

D. Catalase

8. By which of the following mechanisms does lactoferrin affect intracellular bacteria?

A. Damage to microbial membranes

B. Splits mucopeptide in bacterial cell wall

C. Digestion of killed organisms

D. Deprives proliferating bacteria of iron

9. Which of the following bacteria inhibit phagocytic engulfment by the production of

capsules?

A. S. pneumonia

B. Salmonella

C. M. tuberculosis

D. Bacillus anthracis

10. Pyroptosis is a form of cell death which is mediated by which of the following?

A. Caspase 1

B. Caspase 3

C. Caspase 6

D. Caspase 8

Answers

1. D. Page 137

“Some subsets of lymphocytes carry out cytotoxicity (CD8+ T cells and natural killer

cells) while others are important for cytokine production, e.g., Th1 cells (IL-2, IFN-

gamma, and TNF-beta) or Th17 cells (IL-17, IL-21, and IL-22).”

2. C, page 138

“C5a is the most potent pro-inflammatory product formed during complement

activation.”

3. B, page 141, table 5-3

VLA-4 is the ligand for VCAM-1 (CD106).

4. A, page 142, box 5-2

“P-selectin is present in the dense granules of platelets and in the Weibel-Palade bodies

(granules) of endothelial cells.”

5. B, page 143

“ICAM-2 is constitutively expressed at high levels on endothelial cells. Unlike ICAM-1,

the expression of this receptor does not increase on the surface of stimulated endothelial

cells.”

6. B, page 146, box 5-4

“Patients with this disorder [Leukocyte Adhesion Deficiency Type I] have severe,

recurrent infections and die in childhood due to overwhelming infections because of the

defective beta 2 subunit, and thus almost no CD18 will be expressed on the leukocyte

surface membrane.”

7. C, page 148

“A genetic deficiency of the NADPH oxidase system is seen in the primary

immunodeficiency disorder, chronic granulomatous disease (CGD).”

8. D, page 150, table 5-6

Lactoferrin deprives proliferating bacteria of iron during an oxygen-independent

mechanism of intracellular killing.

9. A, page 153, table 5-8

S. pneumonia inhibits phagocytic engulfment by production of capsules.

10. A, page 156

“It [pyroptosis] is a pathway morphologically and mechanistically distinct from other

forms of cell death in which caspase 1 dependence is a defining feature. Unlike

apoptosis, which involves caspase 3, caspase 6, and caspase 8, in pyroptosis caspase 1 is

the enzyme that mediates this process of cell death.”



Chapter 6: B Lymphocytes and Immunoglobulins

Prepared by Autumn Guyer, MD, Massachusetts General Hospital, and Monica Bhagat,

MD, University of Pennsylvania

1. In humans what percent of the serum immunoglobulins are of the kappa variety?

A: 40%

B: 50%

C: 60%

D: 70%

2. Which immunoglobulin has the largest molecular weight in the serum?

A. IgG

B. IgA

C. IgM

D. IgE

3. Immunoglobulins can be cleaved by the proteolytic enzymes papain and pepsin into

definable fragments which include: Fab, F (ab’)2 and Fc. Which of the following is true

regarding the dimeric F(ab’)2 properties of a pepsin treated IgG antibody?

A. Capable of fixing complement

B. Unable to react with receptors on effector cells

C. Unable to bind to specific antigen

D. Crystallizable

4. Which of the following is the high affinity Fc receptor for IgG?

A. CD64

B. CD32

C. CD16a

D. CD16b

5. Which of the following is true regarding IgG subclasses?

A. IgG1 and IgG3 are associated with antibody activity directed at polysaccharide

antigens

B. IgG2 is the most abundant subclass in the serum

C. IgG3 has the longest serum half-life

D. IgG4 is unable to activate the classical complement pathway

6. Which of the following antigens does not elicit a T-cell independent immune

response?

A. Polysaccharides

B. Membrane glycolipids

C. Nucleic acids

D. Prevnar vaccine

7. Which immunoglobulins do not have a dedicated traditional hinge region, which is

defined as a proline-rich region between the CH1 and CH2 domains of the heavy chain?

A. IgG, IgE

B. IgG, IgA, IgM

C. IgE, IgM

D. IgM, IgA

8. Which part of the immunoglobulin structure listed below has four slightly different

constant region sequences resulting in four immunoglobulin subclasses?

A. Heavy chain

B. Kappa light chain

C. Lambda light chain

D. Delta chain

9. What is another name for CD23?

A. Fc-gamma RI

B. Fc-gamma RII

C. Fc-epsilon RI

D. Fc-epsilon RII

10. Which of the following enzymes involved in V, D, and J recombination is ONLY

found in lymphocytes?

A. RAG-2

B. DNA-ligase IV

C. DNA-dependent protein kinase (DNA-PK)

D. Ku protein

Answers

1. C, page 168

“In humans, approximately 60% of the serum immunoglobulins are of the kappa variety

and 40% of the lambda isotype. The identity of the light chain as either kappa or lambda

is determined by the amino acid sequence of the constant region.”

2. C, page 169 and table 6-1

In the serum, IgM generally exists as a pentamer of 5 monomeric subunits held together

by disulfide bonds with a molecular weight of 890,000 kDa.

3. B, page 172, figure 6-8

Pepsin treatment yield 1 dimeric F (ab’)2 and the Fc fragment is cleaved. The F(ab’)2 has

lost most of the specific antigenic determinants since most of these reside in the carboxy-

terminal half of the heavy chain (Fc fragment), is not complement-fixing and does not

react with receptors on effector cells.

4. A, page 179, table 6-3

CD64 also known as the Fc gamma RI receptor, is the high affinity receptor for IgG and

binds more strongly than CD32, CD16a or CD16b.

5. D, page 182, table 6-5

IgG4 does not activate the classical complement pathway. IgG1 is the most abundant

subclass with a normal serum concentration of 540mg/dL. IgG3 has the shortest serum

half-life, around 7 days, thought to be related to the much longer hinge region. IgG1 and

IgG3 are associated with antibody activity directed at protein antigens (diphtheria and

tetanus toxoids) while IgG2 and IgG4 are directed at polysaccharide antigens

(pneumococcal and H. influenzae).

6. D, page 200

“Protein antigens are referred to as T-dependent antigens in contrast to non-protein

antigens, which are referred to as T-independent antigens. The most important TI

antigens are polysaccharides, membrane glycolipids, and nucleic acids, all of which

cannot be processed and presented by APCs in association with MHC molecules;

therefore, they cannot be recognized by T helper cells.” Prevnar is a vaccine that contains

polysaccharides conjugated to a carrier protein, eliciting a T-cell dependent immune

response.

7. C, page 167

“Two immunoglobulin subtypes, IgM and IgE, do not have hinge regions and lack

interchain disulfide bonds in this region; however their CH2 domains perform a hinge-

like function.”

8. C, page 168

“The identity of the light chain as either kappa or lambda is determined by the amino acid

sequence of the constant region. In contrast to the kappa isotype, there are four slightly

different constant region sequences of the lambda light chain, forming four subclasses

(subtypes).”

9. D, page 180

“The low-affinity receptor Fc-epsilon RII (CD23) is a C-type lectin found on B cells,

activated T cells, eosinophils, Langerhans cells, and epithelial cells.”

10. A, page 193

“The set of enzymes needed to recombine V, D, and J segments is generically called

VDJ recombinase. Some of these are lymphocyte-specific and are others are expressed in

many cell types. Two of the enzymes made only in lymphocytes include recombination

activating gene-1 and recombination activating gene-2 (RAG-1 and RAG-2). “



Chapter 7: T Lymphocytes and Cell-Mediated Immunity

Prepared by Fatima Khan, MD, University of Washington, and Meagan W. Shepherd,

MD, Ohio State University

1. In this figure, which surface markers are typical of this cell population indicated by

the blue arrow?

A. CD3- CD4- CD8-

B. CD3- CD4+ CD8-

C. CD3+ CD4- CD8-

D. CD3+ CD4+ CD8+

2. Name one newborn screening method currently being utilized in some states to screen

for a specific immunodeficiency?

A. Microarray chip IgE assay

B. T cell immunophenotyping

C. PCR for TRECS

D. CD40 functional expression assay

3. Lymphocyte enumeration studies reveal a patient with T-B+NK- phenotype. What is

the underlying defect associated with this phenotype?

A. IL-7R deficiency

B. Common gamma chain defect

C. MHC I deficiency

D. ADA deficiency

4. IL-4, IL-5, IL-6, IL-10, IL-13 are secreted by which T cell type?

A. Th1

B. Th2

C. Th3

D. Treg

5. What is the usual ratio of CD4+ T cells to CD8+ T cells?

A. 1:1

B. 1:2

C. 2:1

D. 4:1

6. On what chromosome or chromosomes are the genes for the T cell receptor located?

A. Chromosome 5

B. Chromosome 6

C. Chromosome 2 and chromosome 22

D. Chromosome 7 and chromosome 14

7. Which of the following is a negative regulator of T cell activation?

A. CD28

B. ICOS

C. CD152

D. CD40 ligand

8. Which of the following transcription factors is ultimately suppressed by cyclosporine

and tacrolimus

A. NFAT

B. NF-κB

C. GATA 3

D. RORγt

9. What is the main transcription factor for T-helper 3 cells?

A. T-bet

B. FOXP3

C. RORγt

D. STAT3

10. What is the main cytokine produced by T-helper 3 cells?

A. IL-2

B. IL-17

C. IL-10

D. TGF-β

Answers

1. D, pages 217-18, Figure 7-7

The “upper right quadrant is where double positive T cells are found. These double

positive cells express a fully rearranged T cell receptor….”

2. C, page 222

“T cell receptor-excision circles (TRECS) are the leftover products of TCR

rearrangement during the DP stage that consists of circular DNA containing spliced-out

intervening D, J, and C segments. Thymic output can be monitored by a PCR-based assay

that is sensitive enough to detect TRECS…in the proposed screening program for SCID.”

3. B, page 249. Table 7-5

X-linked SCID common gamma chain defect. “Lacks T cells, NK cells; has B cells”

4. B, page 235

“Th2 cells secrete IL-4, IL-5, IL-6, IL-10, IL-13”

5. C, page 212

“In humans, circulating CD4+ T cells outnumber CD8+ T cells by approximately 2:1.”

6. D, page 215

“In humans, the genes for the T cell receptor are found on chromosome 7 and

chromosome 14….”

7. C, page 232

“The most important negative regulator for global T cell activation is the CTLA4

(CD152) molecule, the high avidity receptor for CD80/26 (also referred to as B-7.1/B-

7.2).

8. A, page 248

“The agents cyclosporine and FK506, or tacrolimus, are known as calcineurin-based

immunosuppressives since they both target the signaling pathway coupling calcium flux

to induction of the transcription factor NFAT, which is critical for IL-2 production in

activated T cells.”

9. B, page 236. Table 7-3

The transcription factor associated with T-helper 3 cells is FOXP3.

10. D, page 236. Table 7-3

The main cytokine produced by T-helper 3 cells is TGF-β.



Chapter 8: The Mucosal Immune System in Health and Disease

Prepared by Kathryn Convers, MD, St. Louis University School of Medicine, and Monica

Bhagat, MD, University of Pennsylvania

1. Which of the following best represents the name and function of M Cells?

A. Microfold Cells; act as antigen-presenting cells

B. Mucosal Cells; where switching of IgM- to IgA-bearing B cells predominate

C. Microfold Cells; luminal antigens are taken up by these cells and are delivered to

adjacent APCs

D. Mediator Cells; such as mast cells and NK cells

2. Which of the following is NOT a region in the GALT where Dendritic Cells may be

found?

A. In a region of the Peyer’s Patch immediately below the M cells, referred to as the

SED

B. In an intraepithelial location as a set of specialized DC subsets that extend dendrites

between the tight junctions of enterocytes that can sample luminal contents

C. In lymphoid follicles scattered throughout the lamina propria

D. In mammary lymphoid tissues

3. Which of the following is NOT an immunoregulatory role of Retinoic Acid in the

mucosal immune system?

A. May capture antigens in the external secretions, at the epithelial surface, or attach to

antigen located within the mucosal lamina propria

B. Induces addressing-associated homing receptors on T and B cells

C. Induces a subset of forkhead box P3 (FOXP3)+ regulatory T cells

D. Provides important signals that induce differentiation and class switching of IgA-

producing B cells

4. Which of the following statements concerning regulatory lymphocytes is FALSE?

A. CD4+ T regs are abundant in mucosal lymphoid tissues, there they downregulate Th1

and Th2 responses.

B. CD4+ Tregs are characterized by CD25 expression, CTLA-4 binding, and by the

production of regulatory cytokines (IL-11 and TGF-alpha).

C. Expression of CD25 on T cells is associated with natural regulatory functions

D. FOXP3 is the key regulatory gene in the development of CD25+ Tregs

5. Which of the following findings are characteristic in patients with selective IgA

deficiency?

A. Recurrent ear infections, sinusitis, bronchitis and pneumonia

B. Autoimmune diseases, such as Rheumatoid Arthritis, SLE and ITP

C. Allergic diseases, such as asthma and food allergies

D. Susceptibility to the development of anti-IgA-related anaphylactoid reactions to blood

transfusions, and other blood or plasma products containing small amounts of IgA

E. All of the above

6. Bronchus-associated lymphoid tissues (BALT) aim to avoid sensitization by inhaled

antigens and this is accomplished in part via which of the following cells?

A. TCR1 T cells

B. Natural killer T cells

C. M cells

D. Goblet cells

7. All of the following cytokines play a role in stimulating production of alpha and beta

defensins except for:

A. IL-1

B. TNF-alpha

C. LPS

D. IL-6

8. Advantages of sublingual immunotherapy (SLIT) include all of the following except:

A. Fewer doctor visits

B. Avoidance of injections

C. Fewer side effects

D. Requires lower concentration of allergen doses

9. Which type of T-cell is predominant in the MALT?

A. Alpha-beta T cells

B. Natural killer T cells (NTK)

C. Gamma-delta T cells

D. Treg cells

10. Which of the following correctly describes lymphocyte recirculation to effector sites

in regards to the gut-associated lymphoid tissues (GALT)?

A. Antigen is captured by M cells transfer of antigen to SED area of Peyer’s patch

cognate interaction with T and B cells migration of these cells out of the Peyer’s patch

through efferent lymphatics to enter the mesenteric lymph nodes (MLN).

B. Transfer of antigen to SED area of Peyer’s patch antigen is captured by M cells

cognate interaction with T and B cells migration of these cells out of the Peyer’s patch

through efferent lymphatics to enter the mesenteric lymph nodes (MLN).

C. Cognate interaction with T and B cells transfer of antigen to SED area of Peyer’s

patch antigen is captured by M cells migration of these cells out of the Peyer’s

patch through efferent lymphatics to enter the mesenteric lymph nodes (MLN).

D. Antigen is captured by M cells transfer of antigen to SED area of Peyer’s patch

migration of these cells out of the Peyer’s patch through efferent lymphatics to enter the

mesenteric lymph nodes (MLN). cognate interaction with T and B cells.

Answers

1. C, page 259

“Of particular importance within the mucosal surface are specialized epithelial cells,

called microfold (M) cells, located in the epithelium overlying follicles of the Peyer’s

Patches. The M cells are characterized by an invagination at the basolateral membrane,

which forms a “pocket” normally occupied by lymphocytes and APCs referred to as the

Subepithelial Dome (SED). There contain all of the immunocompetent cells that are

required for the initial generation of an immune response, i.e., T cells, B cells, and APCs.

Soluble and particulate luminal antigens are taken up by M cells and are delivered to

adjacent APCs”.

2. D, page 261-262

“Of particular importance in mucosal immunity are the DCs, which are found as a

pleomorphic set of several populations of APCs in several sites of the intestine and

associated lymphoid tissues. In the GALT, DCs are found in at least 3 separate locations:

(1) in a region of the Peyer’s Patch immediately below the M cells, referred to as the

SED; (2) in an intraepithelial location as a set of specialized DC subsets that extend

dendrites between the tight junctions of enterocytes that can sample luminal contents; and

(3) in lymphoid follicles scattered throughout the lamina propria.”Additionally,

Mammary-associated lymphoid tissues are separate from Gut-associated lymphoid

tissues (GALT).

3. A, pages 263-264

“Retinoic Acid (RA), produced by gut dendritic cells or from dietary sources, not only

induces addressin-associated homing receptors on T and B cells, but also provides

important signals that induce differentiation and class switching of IgA-producing B

cells. Retinoic acid also induces a subset of fork box P3 (FOXP3)+ regulatory T cells,

which are important for maintaining immune tolerance in the gut.” Page 273: “SIgA may

capture antigens in the external secretions, at the epithelial surface, or attach to antigen

located within the mucosal LP”.

4. B, page 274

“CD4+ Tregs are abundant in mucosal lymphoid tissues, where they downregulate Th1

and Th2 responses. These cells are characterized by CD25 expression, CTLA-4 binding,

and by the production of regulatory cytokines (IL-10 and TGF-beta). Expression of CD25

on T cells is associated with natural regulatory function; CD25 is the alpha-chain of the

IL-2 receptor and is also a marker of T cell activation. FOXP3 is the key regulatory gene

in the development of CD25+ Tregs, which can be induced in the periphery, and their

conversion into Tregs is dependent on TGF-beta.”

5. E, page 283

“Common infections observed in symptomatic patients with selective IgA deficiency are

recurrent ear infections, sinusitis, bronchitis, and pneumonia. People with selective IgA

deficiency may be more susceptible to allergic diseases such as asthma and food

allergies. The spectrum of autoimmune disorders seen in individuals with selective IgA

deficiency include rheumatoid arthritis, systemic lupus erythematosus, and immune

thrombocytopenic purpura. As the case study described in this chapter demonstrates,

patients with IgA deficiency are more susceptible to the development of anti-IgA-related

anaphylactoid reactions to blood transfusions, immunoglobulin replacement therapy, and

the administration of other plasma products containing small amounts of IgA.”

6. D, page 272

“BALT refers to the bronchial lymphoid aggregates and the less-organized lymphoid

tissue in humans and other species. About 10 to 20 percent of the interstitial lymphocyte

pool is composed of T cells. There is a priority to avoid inflammation within the

bronchial lumen or mucosa. TCR1 T cells promote tolerance to inhaled antigens, and also

alveolar macrophages exert an anti-proliferative effect on T cells, preventing antigen

presentation at the mucosal surface.”

7. D, page 261

“These include alpha and beta defensins, which are produced by Paneth cells and

epithelial cells, respectively, and which together provide a protective defensin network

against most bacteria and many viruses. Although…proinflammatory cytokines such as

IL-1, TNF-alpha, and bacterial LPS play a role in their activation.”

8. D, page 283

“It is claimed that the advantages of this immunotherapy include avoiding injections,

fewer doctor visits, and lower side effects. However, the therapy requires four to five

months to yield results. Apparently, SLIT is safe and effective, but perhaps less effective

than injection immunotherapy, since it needs up to 300x higher allergen doses, and its

long-term efficacy is unclear.”

9. C, pages 270-271

“The most common T cell receptor (TCR alpha-beta) is made up of alpha and beta chains

and is found on about 95 percent of circulating T cells. A second type of TCR (TCR

gamma-delta) has gamma and delta chains and is found on about 5 percent of circulating

T cell, but is the predominate cell type in the MALT found within the population of

lymphocytes known as IELs. The gamma-delta T cells are particular in that they do not

seem to require antigen processing and MHC presentation of peptide epitopes for

activation, although some recognize MHC-1B molecules.”

10. A, page 266

“In the case of the GALT, antigen is captured by M cells and is transferred to DCs in the

SED area of the Peyer’s patch (PP) where they engage in cognate interaction with T cells

and B cells. This is followed by the migration of these cells out of the PP through the

efferent lymphatics to enter the local mesenteric lymph nodes (MLN). Activated cells

undergo differentiation, and effector cells travel through lymphatics to enter the

circulatory system through the thoracic duct. From the blood, the T and B cells seed the

lamina propria of the small intestine and mucosae of other remote effector sites.”



Chapter 9: Cytokines, Chemokines, and the Immune System

Prepared by Cindy Salm Bauer, MD, Medical College of Wisconsin, and Meagan

Shepherd, MD, Ohio State University

1. Which of the following cytokines is characteristically produced by Th2 cells?

A. IFN-γ

B. TNF-α

C. Lymphotoxin (LT)

D. IL-4

2. Which of the following originate directly from thymic precursors rather than

peripheral T helper cell precursors?

A. Tr1

B. Th3

C. iTreg

D. nTreg

3. Cytokines sharing the common β chain (βc) belong to which family of receptors?

A. Class I

B. Class II

C. TNF family

D. IL-1/TLR

4. Cytokines that bind members of the TNF family of receptors include:

A. IL-2/IL-4/IL-7

B. IL-1/IL-33/IL-18

C. FasL/CD40L/APRIL/RANKL

D. IFN-β/IL-10

5. Which cytokine signal pathway utilizes SMADs?

A. IL-2

B. TGF-β

C. IL-17

D. TNF-α

6. What is the most potent inducer of TNF-α by monocytes?

A. Lipopolysaccharide

B. ssRNA

C. dsRNA

D. profiling

7. Which of the following has been shown to inhibit production of IL-4?

A. Vitamin A, cysteinyl leukotriene receptor antagonists, and biotin

B. Vitamin D and B-agonists

C. Para-phenylinediamine

D. Vitamin E, aspirin, and parthenolide

8. Which of the following receptors shares the β subunit of the IL-5 receptor?

A. IL-6 receptor and IL-10 receptor

B. IL-4 receptor and IL-13 receptor

C. IL-3 receptor and GM-CSF receptors

D. IL-13 receptor and IL-21 receptor

9. Which of the following does IL-6 use as for secondary signaling?

A. Erk

B. Lyk

C. P40

D. gp130

10. Which of the following is a Type III interferon?

A. IFN-α

B. IFN-β

C. IFN-γ

D. IFN-λ

Answers

1. D, pages 294-295

When activated, Th1 cells produce IFN-γ, TNF-α, LT (also known as TNF-β), and IL-10.

IL-4 is a Th2 cytokine.

2. D, pages 295-296

nTreg cells originate directly from thymic precursors. The other 3 regulatory cells listed

originate from peripheral T helper cell precursors.

3. A, page 301

Cytokines sharing the common β chain (as well as those sharing the common γc and

gp130-utilizing) belong to the Class I hematopoietin cytokine receptor family.

4. C, page 301

FasL/CD40L/APRIL/RANKL bind the TNF family receptors which signal using NF-κB,

TRAF6, MyD88, IRAK, and IRAK4. IL-2/IL-4/IL-7 bind Class I receptors that all share

the common γc chain and signal through JAK/STAT. IL-1/IL-33/IL-18 bind the IL-

1/TLR receptors which signal using TRAF6, MyD88, IRAK, etc. And, IFN-β/IL-10 bind

the Class II receptors that signal through JAK/STAT.

5. B, page 301

TGF-β binds the TGF-β receptors which signal through SMAD. IL-2 signals via

JAK/STAT. IL-17 signals via TRAF6/JNK/Erk/AP-1/NF-ᴋB. And, TNF-α signals via

TRAF6/MyD88/IRAK/NFκB.

6. A, page 343

“The most potent inducer of TNF-α by monocytes is lipopolysaccharide (LPS), acting

through TLR4.”

7. D, page 327, Figure 9-22

“Vitamin E, aspirin, and parthenolide have been shown to inhibit the expression of IL-4,

whereas they have no effects on the production of Th1 cytokines.”

8. C, page 327

“…the β subunit of the IL-5 receptor is also found in IL-3 and GM-CSF receptors….”

9. D, page 329

“IL-6 is probably the best studied of the cytokines that use gp130 in their signaling

complexes. Other cytokines that signal through receptors containing gp130 are IL-11,

IL-27, IL-31, ciliary neurotrophic factor, cardiotrophin-1….”

10. D, page 41

“The recently identified type III interferon group consists of three IFN-λ molecules called

IFN-λ1, IFN-λ2, and IFN-λ3 (also called IL-29, IL-28A, and IL-28B, respectively).:



Chapter 10: Immunogenetics

Prepared by David Scott, MD, Scripps Clinic, Scripps Green Hospital Program, and

Monica Bhagat, MD, University of Pennsylvania

1. Which of the following is not characteristic of MHC class I molecules?

A: Binds peptides of 10-30 residues or more

B: Antigen-binding cleft consists of an a 1 and 2 domain

C: Distributed on all nucleated cells

D: CD8 binds to the 3 region

2. MHC-I and MHC-II molecules are best induced by which cytokine?

A: IFN-gamma

B: TGF-beta

C: IL-10

D:IL-2

3. Match the following diseases with their associated susceptibility-inducing alleles.

i. Ankylosing spondylitis

ii. Celiac disease

iii. Goodpasture

iv. Lupus

v. Rheumatoid arthritis

A. B27, DR11, DR2, Cw6, DR4

B. B27, D51, DR2, DR3, DQ6

C. DR2, DR4, DR3, DR3, DR4

D. B51, DR3, DR2, DR3, DR4

E. B27, DR3, DR2, DR3, DR4

4. Which of the following is not a risk factor for GVHD?

A. HLA mismatch

B. High numbers of T cells transfused from donor

C. Younger age of donor or host

D. Differing genders between donor and recipient

5. For solid organ transplantation, what is the best description of the implication of

recipient antibodies to donor HLA-DR, DQ?

A. Absolute contraindication to transplant

B. High titer is a relative contraindication to transplant

C. Does not affect transplant

D. Can be overcome by antecedent host myeloablative therapy

6. Which region of the MHC includes several genes involved in the complement

cascade?

A: MHC-I

B: MHC-II

C: MHC-III

D: MHC-IV

7. Once endogenous antigens are processed by the proteasome and resultant peptides are

trimmed by cytosolic proteases, what proteins are responsible for translocating the

antigenic peptides to the endoplasmic reticulum?

A. TAP1

B. TAP2

C. Both TAP1 and TAP2

D. Tapasin

8. Which of the following statements is false regarding MHC-II deficiency?

A. There are four known genetic types of MHC-II deficiency.

B. Patients with this disease do not have a laboratory profile consistent with severe

combined immunodeficiency.

C. This disease may lead to the development of autoimmune diseases including

sclerosing cholangitis.

D. There is a complete lack of antibody production in this disease.

9. In processing exogenous antigens, this protein occludes the MHC-II cleft and prevents

peptidases from loading until the molecule is in the lysosomal or late endosomal

compartment containing the peptides.

A. Tapasin

B. CLIP

C. Invariant chain

D. TAP1

10. The following statements about hyperacute rejection of a graft are all true except for:

A. Hyperacute rejection of a graft is due to preformed antibodies to ABO or MHC

antigens on the graft.

B. Hyperacute rejection of grafts occurs more frequently than acute rejection of grafts.

C. In those patients with multiple anti-MHC antibodies, hyperacute rejection may

sometimes be prevented by the use of plasmapheresis of the recipient prior to transplant

D. In hyperacute rejection, pathology is limited to the actual graft itself and does not

involve any of the vasculature of the organ.

Answers

1. A, page 373, Table 10-3

In Summary, MHC-I molecules have the following properties: Polypeptide chains consist

of a single α chain (44–47 kD) noncovalently linked to the β2-microglobulin chain (12

kD). They are present on all nucleated cells. Their antigen-binding clefts are composed

of α1 and α2 domains. Their binding site for T cell co-receptor is CD8 on the α3 region.

The size of the peptide-binding cleft accommodates peptides of 8–11 residues. Whereas,

the MHC-II molecules have the following properties: Polypeptide chains consist of a

single α chain (32–34 kD) noncovalently linked to a single β chain (29–32 kD). They are

present on APC’s. Their antigen-binding clefts are composed of α1 and b2 domains.

Their binding site for T cell co-receptor is CD4 on the b2 region. The size of the peptide-

binding cleft accommodates peptides of 10–30 residues or more.

2. A, page 370

“Interferon-γ (INF-γ) increases the expression of MHC-I or MHC-II molecules and can

induce the expression of MHC-II molecules on certain cell types that do not normally

express them. This may be very important both in normal immunologic function and in

autoimmunity.”

3. E, page 377

Addison’s disease DR3

AS B27

Behcet’s syndrome B51

Celiac disease DR3, DQA1*0501, DQβ1*0201

Congenital adrenal hyperplasia B47

Dermatitis herpetiformis DR3

Graves’ disease DR3

Hashimoto’s disease DR11

Hereditary hemochromatosis A3/B14

Insulin-dependent diabetes mellitus B35, Cw04

Idiopathic membranous GN DR3

MS DR2, DQ6

Myasthenia Gravis DR3

Narcolepsy DR2, DQB1*0602

Psoriasis vulgaris Cw6

Pemphigus vulgaris DRB1*0402-DQB1*0302, DRβ1*1401-DQβ1*0503

RA DR4

SLE DR3

Sarcoidosis DRβ1*1101

4. C, page 382

All of the listed factors are considered to be risk factors for developing GVHD except for

younger age. Instead, older age of donor or host is considered to increase the risk of

GVHD. The reason for this is not further explained in this chapter.

5. B, page 380, Table 10-6

In summary, although the presence of antibodies to HLA-A, B, or C is an absolute

contraindication to transplant, the presence of antibodies to HLA-DR or DQ, even at high

titers, is considered only a relative contraindication. Other autoantibodies cross-reacting

with donor do not typically affect the transplant, unless they are directed at the actual

transplanted organ.

6. C, page 369

“The MHC has three regions: MHC-I, MHC-II, and MHC-III. The MHC-III region

includes several genes involved in the complement cascade (C4A, C4B, C2, and FB), the

TNF-alpha and TNF-beta (LT alpha) genes, the CYP21 gene that encodes an enzyme in

steroid metabolism, the HSP70 gene that encodes a chaperone, and many other genes of

unknown immunological function.”

7. C, page 371

“Endogenous antigens are processed by the proteosome. This complex of proteases

typically generates peptides of four to twenty amino acids with a hydrophobic carboxy

terminus. After trimming of the peptide by cytosolic proteases, the antigenic peptides are

translocated to the ER by the transporters associated with antigen processing (TAP1 and

TAP2 molecule). Tapasin physically links the MHC-I molecules and the TAP

transporters.”

8. D, page 384

“There are four known genetic types of MHC-II deficiency including CIITA, RFXANK,

RFX5, and RFXAP. Patients with MHC-II deficiency do not have severe combined

immunodeficiency because they often produce immunoglobulin and their T cells are

capable of sustaining proliferation after stimulation with mitogens. In spite of this, their

infection pattern resembles that seen in patients with SCID. This is because they have

significant compromise in both functional immunoglobulin production and functional T

cell responses. As is true for many patients with immunodeficiencies, patients with

MHC-II deficiency develop autoimmune disease more frequently than others. Sclerosing

cholangitis is the most common of the autoimmune diseases.”

9.. B, page 373

“The newly synthesized molecules transit the ER and the Golgi. After passage of the li-

loaded MHC-II-DM complex through the Golgi into the late endosomes, the invariant

chain is cleaved by acid proteases, leaving a residual peptide called Class II-associated

invariant chain peptide (CLIP) in the MHC-II cleft. At that point, HLD-DM molecules

remove CLIP from the cleft and stabilize the molecule while the peptide is loaded into

the cleft. The fully loaded MHC-II molecule is recruited to the surface and serves to

stimulate predominantly CD4 positive T cells.”

10. D, page 380

“Hyperacute rejection is due to preformed antibodies to ABO or MHC antigens on the

graft. Hyperacute rejection due to antibodies and complement activation has been one of

the major obstacles to using xenotransplants therapeutically. In hyperacute rejection, the

graft rapidly becomes tender and swollen. Arterioles may also show necrosis or

thrombosis. The goal of the pre-transplant cross-matching is to avoid this type of

rejection and has been responsible for making this complication rather rare. Recent work

using plasmapheresis of the recipient prior to transplant and IVIG, however, has allowed

some patients with multiple anti-MHC antibodies to safely receive a kidney transplant.”



Chapter 11: Advanced in Clinical Immunomodulation

Prepared by Wayne Wolverton, MD, Walter Reed National Military Medical Center, and

Meagan Shepherd, MD, Ohio State University

1. Adverse reactions to IVIG infusion include flushing, nausea, headache, and myalgia.

These effects are most often dependent on what variable?

A. Infusion rate

B. Total dose of IVIG

C. IgA content of IVIG preparation

D. Renal function

2. Lymphocytopenia due to the effects of glucocorticoids are selective and have the

greatest effect this type of lymphocyte in the peripheral circulation.

A. T cells

B. B cells

C. NK cells

D. Plasma cells

3. This agent prevents the dephosphorylation of NFAT by binding FK506 binding

protein (FKBP)-12 which inhibits calcineurin thus inhibiting both T-lymphocyte signal

transduction and IL-2 transcription.

A. Sirolimus

B. Tacrolimus

C. Cyclosporine

D. Mycophenolate mofetil

4. This agent is an IL-1 receptor antagonist approved for treatment of rheumatoid arthritis

and has been shown to be an effective treatment in Familial Mediterranean Fever.

A. Etanercept

B. Abetacept

C. Anakinra

D. Adalimumab

5. By which of the following mechanisms does sirolimus act?

A. Inhibition of calcineurin

B. Inhibition of inosine monophosphate dehydrogenase

C. Inhibition of dihydrofolate reductase

D. Inhibition of mTOR

6. Which of the following immunoglobulins is found in the highest concentration in

IVIG?

A. IgG

B. IgA

C. IgM

D. IgE

7. In nomenclature of monoclonal antibodies, which of the following letters, when

inserted as an infix preceding the –mab stem, denotes primate?

A. u

B. o

C. i

D. a

8. Which of the following suffixes denotes a chimeric monoclonal antibody (contains

>5% mouse protein)?

A. -umab

B. -omab

C. -zumab

D. –ximab

9. Approximately what percentage of lymphocytes undergo intermitotic death following

total body irradiation?

A. 20%

B. 40%

C. 80%

D. 100%

10. Which of the following is an alkylating agent that forms covalent bonds with DNA,

leading to mutations, DNA fragmentation, and cell death?

A. Azathioprine

B. Cyclophosphamide

C. Cyclosporin

D. Mycophenolate mofetil

Answers

1. A, page 397

“The most common side effects include flushing, HA, nausea/vomiting, and myalgias

that are often infusion rate dependent.”

2. A, page 400

“It is noteworthy that lymphocytopenia is selective; i.e., T lymphocytes are depleted from

the circulation to a greater extent than are B lymphocytes [in regard to glucocorticoid

administration].”

3. B, page 404

“…tacrolimus (binds) to the FK506 binding protein. The resulting complex subsequently

bind to calcineurin…involves the inhibition of phosphatase activity of calcineurin and

prevention of NFAT dephosphorylation.”

4. C, page 415

“Anakinra is an IL-1 receptor antagonist that blocks IL-1, a protein involved in the

inflammation and joint destruction associated with RA.”

5. D, page 405

“Unlike the similarly named tacrolimus, sirolimus is not a calcineurin inhibitor. The

mechanism of action of sirolimus is distinct from that of cyclosporine and tacrolimus.

…Sirolimus initially binds intracellularly to the same immunophilin FKBP-12 as

tacrolimus, after producing the immunosuppressive sirolimus-FKBP-12 complex, it

subsequently binds to and inhibits the activation of a regulatory kinase, known as the

mammalian target of rapamycin (mTOR).”

6. A, page 396

“Ninety-five to 99 percent of the IVIG is IgG (with trace amounts of IgA and IgM), and

IgG subclass distribution of approved products is similar to that of normal human serum.”

7. C, page 396, Box 11-2

”The following letters identify the animal source of the product and are inserted as infixes

(i.e., letters inserted into a word) preceding the –mab stem: u – human, o – mouse, a – rat,

e – hamster, i – primate, xi – chimera.”

8. D, page 396, Box 11-2

“The suffix of the product name denotes its class and is based on purity and the degree of

residual foreign protein in the preparation: -umab = human monoclonal antibody (100%

human and contains no mouse protein), -omab = mouse protein (100% mouse protein), -

zumab = humanized monoclonal antibody (contains <5% mouse protein), -ximab =

chimeric monoclonal antibody (contains >5% mouse protein), and –cept = receptor-

antibody fusion protein (receptor attached to Fc of IgG1).”

9. C, page 399

“Following TBI [total body irradiation], 80% of lymphocytes undergo prompt

intermitotic death (i.e., killing of the cells between two successive mitoses during the cell

cycle).”

10. B, page 399

“Cyclophosphamide is an alkylating agent that forms covalent bonds with DNA, leading

to mutations, DNA fragmentation, and cell death.”



Chapter 12: Immunity to Bacteria

Prepared by Bob Geng, MD, UCLA, and Monica Bhagat, MD, University of

Pennsylvania

1. Which of the following is recognized by TLR-2 and unique to the cell wall of Gram-

Positive bacteria?

A. Lipopolysaccharide (LPS)

B. Peptidoglycan

C. Lipoarabinomannan

D. Lipoteichoic acid

2. Phosphatidylinositol 3-phophate (PI3P), a host-membrane component essential in the

synthesis of phagolysomes is blocked by which of the following virulence factors?

A. Lipopolysaccharide (LPS) of Gram-negative bacteria

B. Lysins produced by Shigella and Listeria

C. S. aureus protein A

D. Adhesins including fimbriae and pili

E. Glycolipids in M. tuberculosis

3. Which of the following Toll-Like-Receptors and its corresponding Pathogen-

Associated Molecular Patterns (PAMP) is incorrectly matched?

A. TLR4 recognizes LPS

B. TLR6 recognizes Diacyl lipoproteins

C. TLR9 recognizes Unmethylated CpG DNA of bacteria

D. TLR5 recognizes Lipoarabinomannan

E. TLR2 recognizes Lipoteichoic acids

4. Which of the following is not involved in improving opsonization?

A. Complement C3b

B. IgM

C. IgG

D. Mannose-binding Lectin

E. Complement C3a

5. Which of the following is not an aspect of the Il-23/IL-17 pathway of T-cell-

Macrophage interaction during bacterial infection?

A. Enhanced killing of Intracellular pathogens

B. Induction of epithelial cells to secrete antimicrobial peptides such as beta-defensins

and S-100 proteins

C. Production of granulopoietic and chemotactic factors such as G-CSF and IL-8

D. Production of IL-22

6. Which of the following pathogens produce proteases that cleave sIgA, disrupting

mucosal immunity?

A. Haemophilus influenzae

B. Neisseria gonorrhoeae

C. Mycobacteria tuberculosis

D. Both H. influenzae and N. gonorrhoeae

7. Which of the following types of pathogen-recognition receptors (PRRs) recognize

intracellular bacterial or viral components and leads to direct activation of the

inflammasome?

A. Toll-like receptors (TLRs)

B. NOD-like receptors (NLRs)

C. C-type lectin receptors (CLRs)

D. All of the above

8. In acute bacterial infections, there are two main mechanisms of bacterial clearance by

phagocytes. Which of the following statements is true regarding these two mechanisms?

A. Encapsulated organisms are readily phagocytosed by neutrophils.

B. Encapsulated organisms undergo an enhanced process of phagocytosis through

antibody and complement production.

C. Unencapsulated organisms undergo enhanced phagocytosis by macrophages

medicated by T cells

D. Unencapsulated organisms undergo unenhanced phagocytosis by macrophages only

9. Which of the following pro-inflammatory cytokines is critical for the continuous

recruitment of mononuclear cells into granulomas in order to maintain effective

containment of mycobacterial foci of infection?

A. INF-gamma

B. Macrophage-derived TNF-alpha

C. T cell-derived TNF-alpha

D. Both macrophage-derived and T cell-derived TNF-alpha

10. Which of the following organisms is INCORRECTLY matched with its produced

exotoxin?

A. Escherichia coli and heat-labile enterotoxins

B. Staphylococcus aureus and heat-stable enterotoxins

C. Bacillus anthracis and anthrax toxin

D. Clostridium botulinum and botulinum toxin

Answers

1. D, page 432

Lipoteichoic acid is only found on gram-positive bacteria, and is recognized by TLR-2.

Peptidoglycan is found on gram-positive, gram-negative and mycobacteria (it comprises

a larger portion of the cell wall of gram positives though). Lipoarabinomannan is only

found on the cell wall of mycobacteria. LPS is associated with gram-negative organisms

and is recognized by TLR-4.

2. E, page 437

Glycolipids inhibit PI3P preventing the formation of phagolysosomes to elude

intracellular destruction of the mycobacterium. Lysins help the organism to escape the

phaosome, but does not interfere with PI3P. S. aureus protein A leads to activation of

TNFR1. Adhesins help bacterial invade the host and prevent cell wall exposure to TLRs

and other PRRs. The long chain of LPS prevents complement deposition and membrane

attack complex insertion into the membrane, and the O antigen of LPS allows different

strains of the same species to re-infect the host.

3. D, page 443

TLR5 r ecognizes the flagellin of bacteria. Lipoarabinomannan is part of mycobacteria

and is recognized by TLR2. All the other pairs are correct.

4. E, pages 437-438

Complement component C3a is an anaphylatoxin and is responsible for recruitment and

migration of PMNs. All the other choices are agents that enhance opsonization.

5. A, pages 448-449

The enhanced clearance of intracellular pathogens is mediated by the IL-12/IFN-gamma

pathway. IL-12 release following macrophage phagocytosis of intracellular organism

causes activation of the IL-12R leading to synthesis of IL-2 and subseuqnet synthesis of

IFN-gamma. The binding of IFN-gamma to its receptor leads to the activation of STAT1

and NF-kB pathways to kill the intracellular organism. All the other choices are elements

part of the IL-23/IL-17 pathway that is important in normal bacterial clearance especially

at mucosal surfaces.

6. D, page 437

sIgA protects the mucosal surface against inhaled and ingested bacterial pathogens, many

pathogenic bacteria, such as H. influenzae and N. gonorrhoeae, produce proteases that

cleave IgA, making the molecule ineffective.

7. B, page 442

NLRS are nonmembrane associated PRRs unlike TLRs and CLRs. They recognize

intracellular bacterial or viral components. They discriminate between pathogenic and

commensal bacteria and directly activates the inflammasome. TLRs and CLRs recognize

membrane-bound PRRs only and TLRs activates the inflammasome INDIRECTLY.

8. B, page 445

Nonencapsulated organisms are readily phagocytosed by neutrophils in an opsonin-

unenhanced fashion and are readily killed. In contrast, encapsulated organisms are often

poorly ingested by neutrophils alone; however, with the production of antibody and

complement opsonization, phagocytosis by neutrophils is greatly enhanced and

subsequent killing is permitted. Although Tcell-mediated immune mechanisms can

enhance phagocytosis by macrophages, since such organisms are not regularly

phagocytosed by macrophages, this scheme normally appears to be of relatively lesser

importance.

9. D, pages 450-451

TNF-alpha derived from infected alveolar macrophages initially induces recruitment of a

mixed cellular alveolar and interstitial infiltrate. Under the influence of TNF-alpha and T

cell-derived IFN-gamma, mononuclear cells accumulate to form a highly structured

granuloma. Macrophage and T-cell-derived TNF-alpha is necessary to continuously

orchestrate the recruitment of mononuclear cells into granulomas to contain the

mycobacteria.

10. B, page 433

Exotoxins are proteins released extracellularly into the medium or at local sites in which

it grows. Endotoxins consist of lipid and polysaccharide moieties that form part of the

bacterial cell wall. Certain strains of bacteria produce many exotoxins that are associated

with specific clinical entities. Staphylococcus produces a variety of exotoxins (A, B, C,

D, E and F) that are responsible for staphylococcal food poisoning, enterocolitis,

exfoliative skin disorders, and toxic shock syndrome.



Chapter 13: Mechanisms of Immunity to Viral Disease

Prepared by Marissa Shams, MD, Emory University, and Meagan W. Shepherd, MD,

Ohio State University

1. Toll-like receptors when activated, transmit signals through which domains to induce

transcription of Type I interferons?

A. NLR domains

B. PAMPs

C. TIR domains

D. DNA sensors

2. Which of the following TLR signals through MyD88 independent pathway?

A. TLR3

B. TLR7

C. TLR6

D. TLR9

3. Interferon induces an antiviral state that can inhibit a wide range of viruses. Which of

the following responses is not a mechanism induced by Interferon?

A. Increased production of inactive cellular protein kinase RNA-dependent PKR, which

halts viral and cellular protein synthesis and induces apoptosis.

B. Induced synthesis of RNase and 2’-5’ Oligosynthase. Oligosynthase is activated by

dsRNA and activates RNase to degrade all viral and host mRNA.

C. Induced synthesis of ubiquitin proteasome components involved in protein

degradation.

D. Decreased expression of MHC Class I Molecules.

4. Attachment and Fusion of HIV into target CD4+ cell to gp120/gp41 heterodimer

occurs via:

A. CD4 binding a pocket between V1/V2 & V4

B. CCR5 biding a pocket between V1/V2 & V4

C. CXCR4 binding a pocket on V3

D. CD4 binding a pocket on V3

E. A&B

F. D&C

G. A&C

H. D&B

5. Treg cells regulate important components of the immune system through their

secretion of?

A. IL-17, IL-21

B. IL-10, TGF-B

C. IFN-g, TNF-a

D. IL-6, IL-1

6. Downregulation of MHC-I molecules by viruses makes cells susceptible to killing by

which of the following cells?

A. NK cells

B. Invariant NKT cells

C. Macrophages

D. CD4+ T cells

7. Individuals lacking which receptor tend to be unusually resistant to HIV?

A. CCR3

B. Gp120

C. CCR5

D. CXCR4

8. Lymphocytotropic variants of HIV that use the CXCR4 receptor infect which cells

only?

A. Macrophages

B. CD4+ T cells

C. CD8+ T cells

D. Dendritic cells

9. Which of the following Toll-like receptors acts through both the MyD88 and

TRIF/TICAM pathways?

A. TLR 3

B. TLR4

C. TLR8

D. TLR9

10. Which of the following a Type III interferon?

A. IFN-α

B. IFN-β

C. IFN-γ

D. IFN-λ

Answers

1. C, page 473

“TLRs become activated and transmit signals through their cytoplasmic Toll/Interleukin-

1 Receptor (TIR) domains) resulting in the transcriptional induction of multiple genes

involved in innate and adaptive immunity including Type I Interferons.”

2. A, page 474, Box 13-2

“TLR 3 [uses]TRIF/TICAM [activation cascade] (MyD88 independent).”

3. D, page 476-477

“One of the consequences of interferon signaliging is increased expression of major

histocompatibility molecules, particularly MHC-I, by the target cell.”

4. F, page 483, Figure 13-16

“The binding of CD4 occurs in the pocket between V1/V2 and V4 on gp120, while

binding of chemokine receptors (CCR5 or CXCR4) occurs through V3 on gp41.”

5. B, page 478

“Treg cells elaborate immunosuppressive cytokines, particularly IL-10 & TGF-B. There

has been considerable interest in Treg cells regarding their specific role in protective as

well as tissue-damaging T-cell responses, to several clasess of microbes including

viruses.”

6. A, page 478

“Some viruses may attempt to evade CD8 cytotoxic responses by downregulating the

production of the MHC-I molecules essential for this mode of killing. However, cells

lacking MHC-I molecules are still susceptible to killing by natural killer cells.”

7. C, page 484

“Tropism of HIV-1 has been found to be restricted in individuals lacking CCR5 who are

unusually resistant to HIV infection.”

8. B, page 484

“In contrast, lymphocytotropic variants that infect only

CD4+ cells and use the CXCR4 as a coreceptor are referred to as X4 viruses.”

9. B, page 474, Box 13-2.

TLR 4 uses the MyD88 dependent pathway and also the TRIF/TICAM activation cascade

which is MyD88 independent.

10. D, page 475, Box 13-3

“A Type III interferon has been identified, called

IFN-λ, which binds to a heterodimeric receptor made up of one chain similar to the IL-10

receptor and the other chain representing a totally new and novel IFN receptor.”



Chapter 14: Mechanisms of Fungal Immunity

Prepared by Amanda Jagdis, MD, University of Toronto, and Monica Bhagat, MD,

University of Pennsylvania

1. What type of Pattern recognition receptor (PRR) is most important in innate antifungal

sensing?

A. C-type lectin receptors

B. Toll-like receptors

C. Nod-like receptors

D. Rig-like helicases

2. A 20 year old female patient presents with recurrent oral and vaginal candidiasis, and

chronic dermatophyte infection. The past medical history is significant for hypocalcemia.

There is a family history of candidiasis. Which of the following conditions is most likely?

A. HIV

B. APECED

C. XLA

D. CVID

3. Mutation in which of the following is responsible for Autoimmune

polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)?

A. CD40

B. STAT3

C. AIRE

D. WASP

4. Which of the following cytokine pairs is most involved in promotion of fungal

clearance?

A. IL-10 and TGF-beta

B. IL-4, IL-5, IL-13

C. IL-17, IL-22

D. IFN gamma, TNF

5. A patient presents with difficult to control asthma, and brown sputum. Investigations

reveal bronchiectasis, elevated eosinophil count, and IgE level. Which of the following

organisms is implicated in the pathogenesis?

A. Candida

B. Histoplasma

C. Aspergillus

D. Cryptococcus

6. Which of the following components of the immune system does NOT promote

binding of the fungal organism to the phagocyte surface with subsequent opsonization?

A. Complement

B. Mannose-binding protein (MBP)

C. Collectins

D. NADPH oxidase

7. Which of the following cytokines produced by dendritic cells is critical in activating

CD4+CD25+ Treg cells, which play an important role in ant-fungal resistance?

A. IL-4

B. IL-12

C. IL-10

D. IL-17

8. Indoleamine 2,3-dioxygenase (IDO) is a key enzyme that plays a crucial role in

limiting the inflammatory status of neutrophils. Which of the following cytokines is one

of the main activators of IDO in plasma dendritic cells?

A. IL-5

B. IFN-alpha

C. IFN-gamma

D. IL-17

9. The persistence of Candida albicans as a chronic infection may be due to the IDO-

stimulated production of which of the following cytokines?

A. IL-5

B. IL-10

C. IL-4

D. IL-13

10. Allergic Bronchopulmonary Aspergillosis (ABPA) is due to which type of reaction

involving fungal antigen?

A. IgE-mediated (Type I)

B. Mixed cytotoxic (Type II) and IgE-mediated (Type I)

C. Immunce complex (Type III)

D. Mixed immune complex (Type III) and cell-mediated (Type IV)

Answers

1. A, page 503

C-type lectin receptors and the galectin family are the major PRRs for innate antifungal

sensing.

2. B, page 509

APECED is characterized by chronic mucocutaneous candidiasis, hypoparathyroidism,

and adrenal insufficiency.

3. C, page 509

The AIRE gene is associated with APECED.

4. D, page 505-506

A Th1 response with production of IFN gamma and TNF is central in fungal clearance.

Generation of a dominant TH1 response driven by 12-12 is essential for protective

immunity to fungal infections and involves signature cytokine IFN-gamma. IL-17 and

IL-22 play a controversial role in fungal disease and likely lead to either fungal

immunity or fungal pathology, dependent on various factors.

5. C, page 511

Aspergillus is the organism implicated in allergic bronchopulmonary aspergillosis.

6. D, page 502

Complement, antibodies, MBP, and collectins promote binding of the fungal organism to

the phagocyte surface with subsequent opsonization and represent a recognition

mechanism carried out by a variety of receptors and PRRs that have a hierarchical

organization.

7. C, page 505

An important feature of DCs is their capacity to produce IL-10 in response to fungi.

These IL-10-producing DCs activate CD4+CD25+ Treg cells that are essential

components of antifungal resistance.

8. C, page 508, Figure 14-5

Depicts the metabolic events involved in the activation of IDO in plasma dendritic cells

by a variety of activators, including IFN-gamma, following which the IDO-activated

pDC displays a dual role in both augmenting the suppression of an immune response first

by the induction of naïve Th0 cells into Treg cells through a CTLA-4/B7.1 interaction

and second by the down-regulation of T-effector cells following tryptophan degradation.

9. B, page 510, Figure 14-6

There are two possible mechanisms by which depressed immune function may be

involved in the persistence of C. albicans. In one of these, the IFN-gamma/IDO axis may

accommodate fungal persistence in a host environment by increased IDO resulting from a

host environment rich in IFN-gamma, leading to a rise in Treg cells. In the second

mechanism, high levels of IL-10 may be a consequence of IDO activation by the fungus,

impairing TH1 anti-fungal immunity.

10. D, page 511-512. The combination of a Type I IgE-mediated reaction to Aspergillus

antigen, for example, in an atopic patient together with an immune-complex (Type III)

reaction could result in another type of mixed type hypersensitivity reaction characteristic

of ABPA.



Chapter 15: Clinical Immunology of Parasitic Diseases

Prepared by Kelley von Elton, MD, Walter Reed Medical Center, and Meagan W.

Shepherd, MD, Ohio State University

1. Which of the following is an intracellular protozoan that primarily elicits a Th1

response?

A. Giardia

B. Schistosoma

C. Trypanosoma

D. Leishmania

E. Ascaris

2. Chronic malaria is seen with which protozoa?

A. P. falciparum

B. P. vivax

C. P. ovale

D. A and B

E. B and C

3. What is the most important humoral component of the innate immune response?

A. Properdin

B. C4

C. C3

D. C2

E. IL-12

4. With which parasite do adults harbor greater parasite numbers than children?

A. Whipworm

B. Taenia solium

C. Hookworm

D. Pinworm

E. Toxoplasma

5. What is the mechanism by which Giardia intestinalis performs immune evasion?

A. Antigenic modulation

B. Antigenic variation

C. Molecular mimicry

D. Suppression of host immunity

E. Resistance to complement-mediated lysis

6. Which of the following TLRs (Toll-like receptors) interacts with schistosome double-

stranded RNA?

A. TLR1

B. TLR2

C. TLR3

D. TLR4

E. TLR8

7. Which of the following primary immunodeficiencies is associated with Giardia

infection?

A. IgA deficiency

B. IgM deficiency

C. Hyper IgM

D. Autosomal dominant hyper-IgE syndrome

E. Autosomal recessive hyper-IgE syndrome

8. Red blood cells lacking the Duffy antigen are not susceptible to which of the

following parasitic infections?

A. Plasmodium falciparum

B. Plasmodium vivax

C. Trypanosoma cruzi

D. Trypanosoma gambiense

E. Trypanosoma rhodesiense

9. Which of the following is the most common cause of pathology observed during

helminth infections?

A. Type I Immediate Hypersensitivity

B. Type II Cell-Mediated Hypersensitivity

C. Type III Immune Complex-Mediated Hypersensitivity

D. Type IVA Delayed-Type Hypersensitivity

E. Type V Autoimmunity

10. Which of the following is often asymptomatic in immune-competent individuals but

can become disseminated and cause shock when patients with chronic infection become

immunosuppressed?

A. Strongyloidiasis

B. Microsporidia

C. Cyclospora cayetanensis

D. Cryptosporidium parvum

E. Sarcoptes scabiei

Answers

1. D, pages 522-524

Leishmaniasis is an intracellular protozoa that elicits a Th1 response from the host but

can also elicit Th2 in active cutaneous infections. African trypanosomiasis produces

waves of progeny and is both blood borne and intracellular. Schistosoma incorporates

host antigens on the cell surface of the parasite.

2. E, page 526

P. Vivax and P. Ovale cause chronic infections. P. falciparum causes only acute

fulminating form.

3. C, page 529

The most important humoral component of the innate immune response is the C3

component of complement.

4. C, page 537

Hookworm infections are the exception where adults harbor greater parasite numbers

than children. This suggests hookworms may have unique mechanisms to evade the

host’s response.

5. B, page 547

In Giardia antigenic variation is caused by an exchange of the parasite’s variant surface

protein (VSP). Others that utilize antigenic variation are Plasmodium species and

trichomonas vaginalis.

6. C, page 521

Schistosome double-stranded RNA (dsRNA) interacts with the dendritic cell TLR3.

7. A, page 528

“A definite study of the human immune response to the parasite [Giardia] has not been

possible since most cases of Giardia infection occurs in immunodeficiency patients,

particularly those with an IgA deficiency.”

8. B, page 529

“…red blood cells lacking the Duffy antigen are not susceptible to Plasmodium vivax

infection.”

9. D, page 544

“Delayed-Type Hypersensitivity Type IVA is the most common cause of pathology

observed during helminth infections and is associated with the production by DC4+ T

cells of the Th2 cytokines IL-4 and IL-5 and the subsequent recruitment of eosinophils.”

10. A, page 550, Table 15-6, and page 551

“Strongyloidiasis, often asymptomatic in immune, normal individuals, can become

disseminated when patients with chronic strongyloidiasis become immunosuppressed. It

presents with abdominal pain, distension, shock, pulmonary and neurologic

complications, and septicemia, and is potentially fatal.”



Chapter 16: Immune Deficiency Disorders

Prepared by Kathryn Convers, MD, St. Louis University School of Medicine, and Monica

Bhagat, MD, University of Pennsylvania

1. Which of the following is true of Chediak-Higashi Syndrome (CHS)?

A. Neutrophils of patients have multiple primary granules, and have normal bone

marrow granulocyte release but decreased circulating granulocyte half-life.

B. CHS is a rare autosomal recessive disease characterized by oculocutaneous albinism,

bacterial infections, neurologic abnormalities, and a late onset “accelerated phase”

that is a form of hemophagocytic lymphohistiocytosis (HLH).

C. Phagocytosis is diminished, but chemotaxis is normal or increased; in addition,

antibody-dependent cell-mediated cytotoxicity (ADCC) is diminished, but NK cell

cytotoxicity is intact.

D. Bone marrow transplantation is curative for both the immune defect of CHS, as well

as the neurologic abnormalities.

2. Which of the following genes is not associated with Griscelli Syndrome?

A. Myosin Va on Chromosome 15q21

B. Rab27a on Chromosome 15q21

C. MLPH on Chromosome 2q37.3, F-exon of Myosin Va

D. LYST on Chromosome 1q42-43

3. Which of the following is not true of Hyper IgE Syndrome (HIES)?

A. Many cases are attributable to autosomal dominant or sporadic mutations in the signal

transducer and activator of transcription 3 (STAT3).

B. Patients may present with recurrent infections caused by Staphylococcus aureus,

eczema, elevated IgE level, eosinophilia, delayed shedding of primary teeth, distinct

facial features, osteoporosis and fractures, scoliosis, hyperextensible joints, and

candidiasis.

C. Adults with IgE levels below 2000 IU/mL do not meet diagnostic criteria for HIES,

and do not have susceptibility to infections.

D. Type 2 HIES is an autosomal recessive variant that has been described with elevated

IgE, severe eczema, susceptibility to intracellular bacterial and viral infections, and

deficiency of tyrosine kinase 2 (TYK2).

4. Presence of which of the following is associated with increased risk of developing

diabetes in autoimmune polyendocrine syndrome type 1 (APECED)?

A. HLA-DQ2

B. HLA-DQ6

C. HLA-DQ8

D. None of the above

5. Which of the following is true of Ataxia-Telangiectasia?

A. Patients have elevated levels of serum alpha-fetoprotein, growth retardation,

premature aging, chromosomal instability with an increased frequency of

lymphoreticular cancers, and hypersensitivity to ionizing radiation.

B. In vitro tests of lymphocyte function generally show normal proliferative responses to

T and B cell mitogens.

C. Ataxia typically becomes evident in adolescence.

D. IgA and IgE levels are usually elevated in patients with ataxia-telangiectasia.

6. Severe congenital neutropenia and cyclic neutropenia may both be due to mutations

of what gene?

A. ELA2

B. BTK

C. LYST

D. EVER1

7. Neutrophili-specific granule deficiency is a autosomal recessive disease characterized

by reduction of neutrophil-specific granules and lack of defensins. It can be diagnosed on

peripheral smear because it shows which of the following?

A. Giant granules in neutrophils

B. Platelet clumping

C. Bilobed neutrophil nuclei

D. Add

8. All of the following conditions are associated with defects in chemotaxis except for:

A. Shwachman-Diamond syndrome

B. LAD II

C. LAD III

D. Hyper-IgE Syndrome

9: The complement system provides a bridge between innate immunity and adaptive

immunity. Which of the following biologic products is incorrectly paired with the role it

plays in immunity?

A. C3b and opsonization

B. C5a and chemotactic activity

C. C7 and anaphylatoxic activity

D. C5b-C9 and cytotoxicity MAC

10. A defect in XIAP (X-linked inhibitor of apoptosis) results in which of the following

immune deficiencies?

A. XLP-1

B. XLP-2

C. ITK

D. ALPS

Answers

1. B, pages 566-67

“CHS is a rare multisystem autosomal recessive disease wth oculocutaneous albinism,

frequent bacterial infections, neurologic abnormalities, and a relatively late onset

lymphoma-like “accelerated phase” that is a form of hemophagocytic

lymphohistiocytosis (HLH)”. “Giant granules are seen in neutrophils as a result of

inappropriate fusion of multiple primary granules”. “Chemotaxis is diminished, but

phagocytosis is normal or increased. Impaired bacterial killing is probably due to low

levels and impaired mobilization of primary and secondary granule enzymes. NK cell

cytotoxicity is diminished, but antibody-dependent cell-mediated cytotoxicity (ADCC) is

intact. B cell function appears intact”. “Bone marrow transplantation cutes the immune

defect in CHS and the accelerated phase but it does not prevent the central or peripheral

neurologic problems.”

2. D, page 568, Table 16-2

“Classification of the three types of Griscelli syndrome (GS) in comparison with

Chediak-Higashi syndrome (CHS).”

3. C, page 579

“HIES is an immunodeficiency disorder that, in many cases, is transmitted as an

autosomal dominant trait (Type 1 HIES), but that occurs sporadically in all racial and

ethnic groups. Mutations in STAT3 have been identified as the cause of the autosomal

dominant and sporadic forms of HIES. Patients with this disorder present with recurrent

infections of the skin and lower respiratory system caused by Staphylococcus aureus,

eczema, extremely elevated levels of IgE, eosinophilia, and abdormalities of the

connective tissue, skeleton, and teeth with distinctive facial features, osteoporosis and

fractures, scoliosis, hyperextensible joints, and candidiasis”. “IgE is greatly elevated at

some point in the life of all patients with HIES, but about 20% drop their IgE levels

below 2,000 IU/mL as they get older while retaining their susceptibility to infection”.

“More than one genotype may account for the HIES phenotype. An autosomal recessive

variant (Type 2 HIES) has also been described with elevated IgE, severe eczema, and

recurrent infections, but lacking pneumonias, pneumatoceles, and bony abdnormalities.

A TYK2 deficiency was identified in an AR-HIES patient who presented with

susceptibility of intracellular bacterial and viral infections.”

4. B, page 614. Table 16-6

“Clinical and genetic features of the autoimmune polyendocrine syndromes.”

5. A, page 618. “Ataxia typically becomes evident soon after affected children begin to

walk; the condition progresses until they are confined to a wheelchair, usually by the age

of 10 to 12 years. In addition to cerebellar degeneration, patients with ataxia-

relangiectasia have elevated levels of serum alpha-fetoprotein, growth retardation,

premature aging, chromosomal instability, as increased frequency of lymphoreticular

cancers, and hypersensitivity to ionizing radiation and radiomimetic drugs”. “In vitro

tests of lymphocyte function have generally shown moderately depressed proliferative

responses to T and B cell mitogens”. “The most frequent humoral immunologic

abnormality is the selective absence of IgA, which is present in 50 to 80 percent of

these patients. Hyper-catabolism of IgA also occurs. IgE concentrations are usually low,

and the IgM may be of the low molecular weight variety. IgG2 or total IgG levels may

be decreased, and specific antibody titers may be decreased or normal.”

6. C, pages 565-566. Thirty percent of cases of SCN have dominant mutations in

neutrophil elastase (ELA2). Mutations in this same gene can cause cyclic neutropenia as

well. Both are treated with G-CSF. The BTK gene is mutated in XLA, the LYST gene is

mutated in Chediak-Higashi (CHS), and the EVER1 gene is mutated in

Epidermodysplasia Verruciformis (EV).

7. D, page 569

This condition is characterized by recurrent pyogenic infections of the skin, ears, lungs,

and lymph nodes. Neutrophils are slightly larger and paler than normal upon peripheral

smear. Also, neutrophil morphology is abnormal with bilobed neutrophil nuclei, known

as the pseudo-Pelger-Huet anomaly.

8. D, pages 573-574

There a group of molecular defects that come under the general heading of leukocyte

adhesion deficiency which results in defective leukocyte movement from the blood into

tissues. LAD II is a rare autosomal recessive disease due to mutations in FUCT1. LAD

III is due to mutations in CAL DAG-GEF1. Shwachman-Diamond syndrome is due to a

defect in the SBDS gene and is associated with pancytopenia, exocrine pancreatic

insufficiency, and chondrodysplasia.

9. C, page 581

The three complement pathways, once activated, result in the cleavage of C3 components

and utilize a final common pathway to generate important biologic products. These

include C3b (opsonization), C3a and C5a (anaphylatoxic activity), C5a (chemotactic

activity), and C5b-C9 (cytotoxicity MAC).

10. B, pages 611-612 and Table 16.5 on 612

Immune dysregulation in patients is expressed not only by their susceptibility to

infections but also by an increased risk of allergy, autoimmunity, autoinflammatory

disorders, or malignancy. The lymphoproliferative syndromes are each triggered by EBV

infection, and include XLP-1, XLP-2, and ITK. A defect in XIAP results in XLP-2.



Chapter 17: Mechanisms of Immunologic Injury


1. The Type I hypersensitivity reaction is mediated by which antibody?

A. IgA

B. IgG

C. IgM

D. IgE

2. Which of the following reactions is characterized by cell death which begins with the

binding of antigen-specific antibody with a target cell?

A. Type I hypersensitivity

B. Type IIA hypersensitivity

C. Type IIB hypersensitivity

D. Type IIC hypersensitivity

3. Which of the following is an example of a Type IIA hypersensitivity reaction?

A. Myasthenia gravis

B. Graves’ disease

C. Autoimmune urticaria

D. Hemolytic anemia

4. Which of the following describes a Type IIC hypersensitivity reaction?

A. Anaphylactic

B. Antibody-mediated cytotoxic

C. Antibody-mediated neutralizing

D. Antibody-mediated stimulatory

5. Which of the following types of reactions characterizes an Arthrus reaction?

A. Type IIIA hypersensitivity

B. Type IIIB hypersensitivity

C. Type IVA hypersensitivity

D. Type IVB hypersensitivity

6. Which of the following types of hypersensitivity reaction does not involve humoral

immunity but is largely mediated by T lymphocytes?

A. Type I hypersensitivity

B. Type II hypersensitivity

C. Type III hypersensitivity

D. Type IV hypersensitivity

7. Type IVC hypersensitivity reactions are mediated by which of the following subtypes

of T cells?

A. Th1 cells

B. Th2 cells

C. Th17 cells

D. CD8+ cytotoxic cells

8. Which of the following types of reactions has granulomas as a prominent clinical

feature?

A. Type IVA hypersensitivity

B. Type IVB hypersensitivity

C. Type IVC hypersensitivity

D. Type IVD hypersensitivity

9. Which of the following states describes optimum binding of antibody with antigen and

allows for extensive lattice formation of antigen-antibody complexes?

A. Zone of antibody excess

B. Zone of equivalence

C. Zone of antigen excess

D. Zone of lattice formation

10. Which of the following types of reaction is responsible for the late reaction observed

in allergic patients after immediate skin-prick testing?

A. Type IVA hypersensitivity

B. Type IVB hypersensitivity

C. Type IVC hypersensitivity

D. Type IVD hypersensitivity

Answers

1. D, page 664

“The Type I reaction in the human is mediated by IgE antibodies (formerly referred to as

“reaginic” antibodies).”

2. B, page 666

“In the cytotoxic subtype of Type II hypersensitivity (Type IIA), the consequences of cell

death begin with the binding of antigen-specific antibody with a target cell.”

3. D, page 664, Table 17-1

Hemolytic anemia is an example of a Type IIA hypersensitivity reaction.

4. D, page 668

“Type IIC hypersensitivity reactions are characterized by cytostimulation as a result of

the enhancing effect of an autoantibody directed to a normal cell receptor, resulting in the

pathologic stimulation of the target cell with a pathologic overproduction of a cell

product, e.g., a hormone.”

5. A, page 670

“With immune complex deposition, two manifestations of the mechanisms of tissue

injury have been described: (1) a localized (Arthrus reaction; Type IIIA) and (2) a

systemic (serum sickness; Type IIIB) reaction.”

6. D, page 673

“The fourth major mechanism of immunologic injury is the cell-mediated (delayed

hypersensitivity) or Type IV reaction. Unlike the previous three mechanisms [Types I, II,

and III], this response does not involve humoral antibody but is mediated primarily by the

action of T lymphocytes.”

7. C, page 676

“Following uptake and processing of antigen by dendritic cells, naïve Th0 cells not only

undergo maturation to Th17 cells under the influence of the combined actions of IL-1β,

IL-6, and TGF-β, but also the stabilization and further expansion of these cells is

indirectly provided by the dendritic cell/macrophages derived IL-23.”

8. A, page 674

“The chronic persistence of antigen incapable of elimination promotes the development

of a prominent Type IVA reaction and subsequent formation of granuloma, a collection

of organized cells, mainly macrophages with an infiltrate of lymphocytes of other

leukocytes.”

9. B, page 670, Box 17-1

“In the…zone of equivalence, the binding of antigen with antibody is optimal and

extensive lattices are formed by the cross-linking of large antibody-antibody complexes

that precipitate in the bottom of the tube with neither antigen nor antibody detected in the

supernatant fluid.”

10. B, pages 674-675

“The type of injury [Type IVB hypersensitivity] is seen in many clinical conditions such

as the late reaction observed in allergic patients after immediate skin-prick testing. This

late reaction is part of the late component of the dual “early” and “late” IgE-mediated

skin reaction that waxes and wanes during the several-hour course of a Type I-mediated

reaction.”



Chapter 18: Allergic Diseases and Asthma

Prepared by Monica Bhagat, MD, University of Pennsylvania, and David Scott, MD,

Scripps Clinic/Scripps Green Hospital Program

1. Which of the following statements is FALSE regarding the IgE antibody?

A. IgE antibody is made up of two light chains and two isotype-specific heavy chains.

B. IgE crosses the placenta.

C. About half of the total IgE resides in the intravascular compartment, with the other

half found in tissues (primarily bound to mast cells).

D. The half-life of IgE in peripheral blood is about 1- 5 days but may persist in tissues

for months when bound to its receptor on mast cells.

2. IgE production requires the coordinated interaction of APCs, T cells, and B cells. The

reciprocal T/B cell activation cascade requires three stimulatory signals. Which of the

following is NOT one of these signals?

A. Interaction of co-stimulatory interactions between upregulated molecules on B cells

with those on CD4+ T cells (CD80/CD86 with CD28).

B. Peptides are presented to a naïve Tho cell through its TCR in the context of MHC-II

with the participation of the CD4 co-receptor

C. The stimulation of macrophages by IFN-γ and TNF-β allows more efficient antigen

presentation.

D. This signal is a cytokine-induced phase brought about by the activation of naïve T

cells by IL-2, IL-4-mediated Th2 differentiation, and the production of IL-4, IL-5, IL-

9, and IL-13 that provide additional signals to B cells required to drive IgE synthesis

3. During which phase of the allergic response do mast cells undergo degranulation?

A. Elicitation

B. Challenge

C. Sensitization

D. Priming

4. Which of the following agents results in IgE-independent antibody-mediated

anaphylaxis?

A. Latex

B. Opioids

C. IVIG infusion

D. Dialysis membranes

5. Celiac disease is an example of a non-IgE mediated food disorder. Which of the

following statements is NOT true?

A. The pathogenesis of this disease is caused by the generation of autoreactive T cells.

B. In this disease, autoantibodies are generated against human tissue transglutaminase.

C. In celiac disease, genetically susceptible individuals include those expressing MHC-

II-associated HLA-DR2 or DR8.

D. On a pathological level, this disease affects all layers of the gastrointestinal wall, but

particularly leads to a damaged submucosal layer.

6. Which of the following protein allergens is an enzyme protease from egg white?

A. Trypsin

B. Lysozyme

C. Papain

D. Vicilins

E. 2S albumins

7. Which of the following statements is true?

A. Proteins with linear IgE-binding epitopes generally constitute more effective

allergens than those with conformational variations in three-dimensional structures.

B. All antigens are allergens but not all allergens are antigens.

C. Of the five immunoglobulin isotypes, IgA displays the lowest serum concentration,

with a peak concentration at 10 to 15 years of age in nonatopic individual

D. IL-4 is strong chemoattractant for eosinophils.

E. Allergens are named using the first three letters of the Phylum.

8. Which of the following is true regarding mast cells and basophils.

A. MCT mast cells contain both tryptase and chymase and are found predominantly in

the skin.

B. Basophils are typically found in tissue and migrate to the blood upon activation.

C. Upon activation, mast cells, unlike basophils, are capable of producing

prostaglandins.

D. Mast cells and basophils utilize the Fc R1 for IgE-dependent activation.

E. Both c and d

9. The following would not be expected to be secreted in high levels by Th2 cells:

A. IL-4

B. IL-5

C. IL-9

D. IL-12

E. IL-13

10. Aspirin-induced asthma is an example of what category of drug reaction?

A. Primary side effect

B. Secondary side effect

C. Idiosyncrasy

D. Allergic hypersensitivity

E. Non-allergic hypersensitivity

Answers

1. B, page 690

IgE neither crosses the placenta nor activates complement.

2. C, page 690, Figure 18-4

Signal 1 is outline in choice (b), followed by signal 2 outlined in choice (a), followed by

signal 3 outlined in choice (d). Choice (c) is not part of the signal cascade.

3. B, pages 698-699

The allergic response occurs in a cascade of sequential events known as sensitization,

challenge, and elicitation. In sensitization, a person is exposed to the allergen, and in a

Th2 cytokine-rich environment, this leads to allergen-specific IgE production. These

specific IgE antibodies can now bind the high-affinity IgE receptors on the surface of

mast cells and basophils. These cells are now considered “primed”. Upon re-exposure to

the allergen, the person enters the second phase known as the challenge phase. In this

phase, the allergen interacts with specific IgE molecules bound to the high-affinity FcERI

receptors on mediator cells. Cross-linking of two adjacent FcERI leads to degranulation

of these cells with release of mediators that causes allergic reactions. Degranulation

occurs in the challenge phase. The release of inflammatory mediators and subsequent

allergic reactions is the third phase and is called the elicitation phase.

4. C, pages 716-717, Table 18-18

IgE-independent mediator release is presumably triggered by interactions between

antigen-specific IgG antibodies or immune complexes and Fc receptors on the surface of

mast cells. Remember, Opioids, along with muscle relaxants and vancomycin can result

in non-specific degranulation of mast cells and basophils in a non-allergic nonantibody-

mediated reaction.

5. D, pages 729-730

Celiac disease is a food allergic disorder directed to dietary glutens from wheat, barley,

rye, and sometimes oats. It is due to the generation of autoreactive T cells. Disease is

confined to the mucosa of the small intestine and is characterized by T lymphocyte-

mediated injury and eventual destruction of fingerlike projections, called villi, where

absorption of key nutrients normally takes place.

6. B, pages 689, Table 18-1. In Summary, all of the proteins listed are various allergens.

Lysozyme is an enzyme protease from egg whites. Other major allergens in egg white

include ovalbumin, conalbumin, and ovomucoid, which is the most clinically relevant.

Trypsin is an enzyme protease from dust mite. Papain is an enzyme protease found in

papaya, pineapple and kiwi. Vicilins are a type of seed storage protein from peanuts,

sesame seeds, tree nuts and legumes. 2S albumins are seed storage proteins found in

mustard, brazil nut and walnut.

7. A, pages 687-688

Statement B should read, “All allergens are antigens but not all antigens are

allergens.”

Statement C should read, “Of the five immunoglobulin isotypes, IgE displays the

lowest serum concentration, with a peak concentration at 10 to 15 years of age in

nonatopic individuals.”

Statement D should read, “IL-5 is a strong chemoattractant for eosinophils.”

Statement E should read, “Allergens are named using the first three letters of the

Genus.”

8. E, pages 692 and 703-704 ?

Upon activation, mast cells, unlike basophils, are capable of producing prostaglandins.

Also, mast cells and basophils utilize the FcεR1 for IgE-dependent activation. MCT mast

cells demonstrate predominantly tryptase activity and are found mostly in the airways and

small bowel mucosa. Basophils are typically found in the blood and migrate to the tissue

upon activation.

9. D, page 698

IL12 is released from TH1 cells. All of the others are released from Th2 cells.

10. E, page 718, Table 18-9

Aspirin-induced asthma is an example of a nonallergic hypersensitivity reaction, similar

to radiocontrast allergy. Allergic hypersensitivity reactions involve IgE, which aspirin-

induced asthma does not. Primary side effects are a result of a drug’s primary

mechanism of action, such as drowsiness with antihistamine. Secondary side-effects are

due to an additional effect of a drug, such as candidiasis following an antibiotic.

Idiosyncratic reactions are not immunologically mediated (ie – not hypersensitivity

reactions) and are independent of pharmacologic properties of the drug, such as G6PD

deficiency associated hemolytic anemia.



Chapter 19: Tolerance, Autoimmunity, and Autoinflammation


1. Which of the following terms refers to a specific immunological unresponsiveness to

an antigen resulting from a previous exposure to the same antigen?

A. Antigenicity

B. Tolerance

C. Allergenicity

D. Immunodeficiency

2. Anergy refers to which of the following?

A. T cell clones that are unable to respond to an antigenic stimulus

B. B cells that are unable to produce immunoglobulin

C. Induction of double negative T cells upon exposure to stimulus

D. Activation of the Fas pathway

3. Which of the following molecules has the highest affinity when binding with

CD80/86?

A. MHC-I

B. MHC-II

C. CD28

D. CTLA-4

4. Which of the following diseases can be caused by a mutation to the Fas or Fas ligand

gene?

A. X-linked lymphoproliferative syndrome

B. Severe combined immunodeficiency (SCID)

C. Autoimmune lymphoproliferative syndrome (ALPS)

D. Wiskott-Aldrich syndrome

5. Which of the following cytokines are the most important in suppressing the immune

response?

A. IL-3 and IL-5

B. IFN-gamma and IL-1

C. IL-2 and IL-4

D. TNF-β and IL-10

6. Autoimmune Polyglandular Syndrome Type I (APS-1) is caused by a mutation or

absence of which of the following?

A. Autoimmune regulator (AIRE)

B. Fas

C. WASp protein

D. STAT 3

7. Which of the following is the proposed self-antigen in Wegener’s granulomatosis?

A. Thyrotropin receptor

B. Nuclear antigens (SSA, SSB)

C. Proteinase 3 (c-ANCA)

D. Citrulinated peptides in the joint, IgG

8. Which of the following MHC-associations is found with multiple sclerosis?

A. HLA-B27

B. HLA-DR2

C. HLA-DR4

D. HLA-B13

9. Which of the following drugs is not implicated in causing high rates of drug-induced

lupus erythematosus?

A. Hydralazine

B. Amoxicillin

C. Procainamide

D. Isoniazid

10. True or False: B cells that bear receptors capable of recognizing self-antigens are all

eliminated in the bone marrow?

Answers

1. B, page 769

“One of the most important immunologic principles required for an understanding of

autoimmunity and autoimmune disease is the concept of tolerance, which refers to

specific immunological unresponsiveness to an antigen resulting from a previous

exposure to the same antigen.”

2. A, page 773

“One of the major mechanisms that the human body uses to inactivate self-reactive T cell

clones that have escaped central and peripheral clonal deletion is anergy. By definition,

anergy refers to T cell clones that are unable to respond to an antigenic stimulus.”

3. D, page 774

“CTLA-4, a homologue of CD28, also binds the CD80/86 ligands, but with greater

affinity than CD28, resulting in the inhibition and negative regulation of T cell

activation.” MHC molecules do not bind with CD80/86.

4. C, page 773

“There is another rare human disease called autoimmune lymphoproliferative syndrome

(ALPS) that is caused by mutations similar to the lpr mouse mutations in either the Fas or

Fas ligand gene (termed ALPS 1a and 1b respectively). Patient with these mutations have

significant lymphadenopathy and also produce an array of autoantibodies.”

5. D, page 775

“The reactivity of T cells is under the influence of immunoregulatory cells either through

direct cell-cell interaction or through the secretion of cytokines, e.g. transforming growth

factor (TGF)-β and IL-10.”

6. A, page 770

“…T cells that recognize autoantigens on the surface of the thymic epithelial cells

undergo apoptosis, thus preventing peripheral autoimmunity. These autoantigens are

proteins derived from a diversity of tissues and organs and are expressed on the thymic

epithelial cells at least partly under the regulation of the transcription factor autoimmune

regulator (AIRE).”

7. C, page 779, Table 19-2

Wegener’s granulomatosis is thought to be caused by self-antigens to proteinase 3 (c-

ANCA).

8. B, page 781, Table 19-4

Multiple sclerosis is associated with HLA-DR2.

9. B, page 782

“Of the thirty medications known to cause drug-induced lupus, the three that most

commonly cause the condition are hydralazine, procainamide, and isoniazid.”

10. False, page 777

“…although B-cell receptor rearrangement in the bone marrow is similar to T-cell

receptor rearrangement, B cells that bear receptors capable of recognizing self-antigens

are not necessarily eliminated in the bone marrow through negative selection. Some of

these still-maturing self-reactive B cells exit the bone marrow and relocate peripherally to

the spleen, where they reside initially in T cell zones.”



Chapter 20: Immune Responses to Cancer

Prepared by Monica Bhagat, MD, University of Pennsylvania

1. There are four groups of peptides that classify as TATAs (TAAs) or tumor-associated

transplantion antigens. Which of the following is not representative of these four groups?

A. Unique tumor-specific antigens

B. Over-expressed self-antigen peptides/proteins

C. Shared tumor antigens

D. Bacterial-associated antigens

2. Which of the following innate immune cells play a key role in tumor immunity by

taking up tumor antigens and migrate to lymphoid organs where presentation of

processed peptides to T cells occurs?

A. Mast cells

B. NK cells

C. DCs

D. Basophils

3. Antibodies can play a direct role in KILLING tumor cells via the activation of what

key component of the innate immune system?

A. Membrane-attack complex (MAC)

B. Dendritic cells

C. Mast cells

D. Basophils

4. Which of the following is an example of a previously suppressed embryonic antigen?

A. CEA

B. MAGE tumor-associated antigen

C. HPV

D. P53

5. The following homeostatic immune actions are favored in the premalignant state by

TGF-B EXCEPT:

A. Apoptosis of premalignant cells

B. Downregulation of tumorigenic inflammation

C. Cytostasis

D. Inhibition of effector cells

6. Which of the following is FALSE regarding the enzyme Indoleamine-2,3 dioxygenase

(IDO)?

A. It converts tryptophan to kynurenine

B. It is only produced by mast cells

C. It plays a role in the inactivation of the tumor suppressor gene Bin1

D. It is upregulated in plasmacytoid DCs leading to the activation of Tregs

7. In pathological differentiation of myeloid cells, immature myeloid cells may

differentiate into myeloid-derived suppressor cells (MDSCs). These MDSCs express

which of the following immune suppressive factors?

A. Arginase 1

B. iNOS

C. ROS

D. All of the above

8. T regulatory cells are crucial in cancer immunology, in the sense that regulatory T cell

mediated immunosuppression is one of the most crucial tumor immune-evasion

mechanisms. Which of the following subset of Treg cells is INCORRECTLY identified

by its marker?

A. Natural Treg (nTreg) = CD4+CD25+FOXP3+

B. Induced Treg (iTreg) = CD4+IL10+FOXP3+

C. TH3 cells = CD4+TGF-B+

D. d. TR1 cells = CD4-CD25+FOXP3+

9. In conventional immunotherapy, one can aim to mimic cytokines or block cytokines

and/or inhibit their particular pathway. Out of the following cytokines, which one do

scientists aim to INHIBIT?

A. TGF-beta

B. IL-5

C. IFN-alpha

D. IL-7

10. Which of the following monoclonal antibodies is INCORRECTLY paired with its

target?

A. Cetuximab and EGFR

B. Trastuzumab and HER2

C. Bevacizumab and VEGF

D. Canakinumab and IL-12

Answers

1. D, page 802, Table 20-1

Viral-associated antigens make up the fourth category of TAAs and include HPV, HBV,

and EBV.

2. C, page 806

Dendritic cells play a crucial role in the interface between innate immunity and adaptive

immunity via such presentation of processed peptides to T cells. Mast cells,

macrophages, and even the DCs may be considered sentinel cells that are pre-stationed in

tissue where they continuously monitor the microenvironment.

3. A, page 812

Antibody directed to TAA together with the activation of the complement systemc can

kill the cancer cell by cytolytic activation of the MAC cascade. However, alternatively,

TAA complexed with antibodies as Ag-Ab complexes can interfere with the CTL-killing

of a cancer cell by blocking its activity. So antibodies directed against TAAs can either

facilitate the killing of tumor cells or paradoxically enhance their growth.

4. A, page 802-803, Table 20-1

CEA is a type of tumor antigen that is a part of the category called “overexpressed self

antigen peptides”. These include CEA and Muc-1 (colorectal cancer), Her-2/neu (breast

cancer), and EGF receptor (colorectal, lung, head, and neck cancers). MAGE is shared

among different tumors and is in the “shared tumor antigen” category, HPV is in the

“viral-associated antigen” category, and p53 is part of the “unique tumor-specific

antigen” category.

5. D, page 820. Fig 20-21

TGF-B inhibits immune effector cells in the malignant progression stage, when TGF-B

is functioning as a tumor promoter. TGF-B is considered a tumor supporter during the

metastasis stage.

6. B, page 816

IDO is a key enzyme that converts Trp to Kyn and is involved in tumor growth and

immune suppression. It does this by inactivating Bin1 and via the activation of Treg cells

and blunting of T effector cell function. It is produced by alternatively activated

macrophages and other immunoregulatory cells.

7. D, pages 818-819

In the setting of infection, trauma, immunosuppression, or autoimmunity, a partial block

in IMC differentiation results in their abnormal expansion. Such pathologic conditions

can then lead to the differentiation into MDSCs which produce STAT-induced arginase

1, iNOS, and ROS. MDSCs are defined as CD14-CD11b+ cells that express CD33 but

lack expression of markers found on mature cells. Key to note is that in response to

tumor derived factors, the MDSCs will differentiate into TAMs (tumor-associated

macrophages) which contributes to non-specific T cell suppression.

8. D, page 811, Table 20-3.

T regulatory 1 cells, or TR1 cells, are synonymous with induced Treg cells (iTreg).

TR1 cells are CD4+IL- 10+FOXP3+. Recall that there are CD4+ based Treg cells

and CD8+ Treg cells. Some arise in the thymus, like the nTreg cells, while others arise in

the periphery, like the iTreg and CD8+IL-10+ Treg cells.

9. A, page 822, Table 20-4

IFN-alpha, along with IL-5, IL-7, and IL-21 have all been studied extensively by

seeing if trial administration of such cytokines or recombinant forms of such cytokines

can lead to the destruction of cancerous cells. The toxicity of utilizing interferons in

general, however, has limited the use of recombinant IFN-alpha. TGF-B plays a pivotal

role in tumor development, functioning as a tumor suppressor in the pre-malignant state

and evolving to function as tumor promoter and eventually tumor supporter in the

metastatic stage. Consequently, research is focused on antagonism of TGF-beta.

10. D, page 821, Table 20-5

Canakinumab targets IL-1 beta and was approved by the FDA in 2009 for use in

CAPS (cryopyrin-associated periodic syndromes).



Chapter 21: Lymphoproliferative Disorders: Monoclonal Gammopathies and Neoplasms of the Immune System

Prepared by Bob Geng, MD, UCLA, and Monica Bhagat, MD, University of

Pennsylvania

1. Thalidomide is an old drug that has been rediscovered to have a new function in the treatment of multiple myeloma. There are multiple proposed mechanisms of the action of Thalidomide. Which of the following is NOT a likely mechanism of action?

A. Inhibition of myeloma cell adhesion to bone marrow stromal cells

B. Blocking of Il-6, TNF-alpha, and IL-1beta secretion from bone marrow stromal cells

C. Inhibition of VEGF and Beta-FGF in the stimulation of bone marrow

neovascularization

D. Induction of IL-2 and IFN-gamma release from T-cells

E. Acts as a intracellular proteasome inhibitor for myeloma cells

2. A patient diagnosed with multiple myeloma would like to know his prognosis of

survival. His serum calcium is 12 g/dL, Hemoglobin is 9.5 g/dL, serum beta-2

microglobulin is 6 mg/L, and his albumin is 2.5 g/dL. According to the latest

International Staging System (ISS), what is his approximate average length of survival?

A. 3 years

B. 62 months

C. 44 months

D. 29 months

E. 2 months

3. A patient diagnosed with Monoclonal Gammopathy of Undetermined Significance

(MGUS) is inquiring about his risk of progressing to Multiple Myeloma. Which of the

following features would not suggest a greater risk of progression?

A. Serum free kappa/free lambda ratio of 1.8

B. Urine free kappa/free lambda ratio of 5

C. Serum free kappa/free lambda ratio of 0.2

D. Urine free kappa/free lambda ratio of 0.3

E. Serum free kappa/free lambda ratio of 1

F. Presence of circulating myeloma plasma cells.

4. Rituximab is an anti-CD20 monoclonal antibody that has been used for the treatment

of lymphoma and various autoimmune disorders. Which of the following stages of B cell

development does Rituximab NOT target?

A. Mature B cell

B. Germinal Center B cell

C. Memory B cell

D. Plasma cell

E. Immature B cell

F. Pre B cell

G. Choices A and C

H. Choices D and E

I. Choices F and D

J. Choices C and F

K. Targets all stages.

5. A patient has recently been diagnosed with Hodgkin’s Lymphoma, and received a

lymph node biopsy that is being processed for staining of specific cell surface markers.

On typical H&E stain you notice many bilobed nuclei cells that have a distinct “owl’s

eye” appearance. What would you predict would be the pattern of immunohistologic-

staining of cell surface markers expressed on those particular cells?

A. CD30+/CD15+/CD20+/CD45+

B. CD30-/CD15+/CD20-/CD45+

C. CD30+/CD15+/CD20-/CD45-

D. CD30+/CD15-/CD20+/CD45-

E. CD30-/CD15-/CD20-/CD45-

6. In protein electrophoresis, which of the following conditions may result in an

abnormal elevated gamma globulin pattern?

A. Cirrhosis

B. Chronic infection

C. Various autoimmune diseases

D. All of the above

7. Which of the following statements regarding smoldering multiple myeloma (SMM) is

FALSE?

A. Associated with a lower probability of evolving to MM when compared to MGUS

B. Serum M protein is > or equal to 3 g/dl

C. Bone marrow plasma cells > or equal to 10 percent

D. Absence of anemia, hypercalcemia, lytic bone lsions, renal insufficiency

8. Reed-Sternberg (RS) cells are large and are either multinucleated or have a bilobed

nucleus. RS cells may be found in which of the following conditions?

A. Classical Hodgkin’s lymphoma

B. Non-Hodgkin’s lymphoma (rarely)

C. Mononucleosis

D. Drug-induced reactive lymphadenopathy

E. All of the above

9. Each of the following are examples of techniques used to diagnose the monoclonal

gammopathies EXCEPT:

A. Immunoelectrophoresis

B. Immunofixation

C. Determination of urinary protein

D. FISH assays

E. Determination of relative amounts of kappa and lambda chains

10. POEMS is NOT characterized by which of the following?

A. Peripheral neuropathy

B. Endocrinopathy

C. Thrombocytopenia

D. Association with Castleman’s disease

Answers

1. E, pages 840-841. See Figure 21-15.

2. D, pages 838-839. See Table 21-7.

3. E, pages 834-835. See Table 21-2.

Higher incidence of MM occurs in those patients with abnormal ratio of either < 0.26 or

> 1.65.

4. I, pages 848-849. See Figure 21-17.

5. C, page 855. See Figure 21-8.

6. D, pages 831-832

Hypergammaglobulinemia is a non-specific finding that may be due to a broad

differential of conditions. The classic “M spike” is present in patients with multiple

myeloma due to a restricted increase of a monoclonal immunoglobulin product (single

clone). Of note, this “M” component may be either an intact immunoglobulin (IgA, IgG,

IgD, or IgE) or a Bence-Jones protein (free kappa or free lambda chains).

7. A, pages 837-838.

SMM is associated with a HIGHER probability of evolving to MM when compared to

MGUS.

8. E, pages 854-855

HL is a B cell neoplasm characterized by a minority of neoplastic cells, the RS cells,

which are located within an extensive infiltrate of reactive cells. Although necessary for

the diagnosis of HL, it is not sufficient, and RS cells are actually also present in other

conditions, as listed above. They are RARELY found in NHL.

9. D, pages 831-834

FISH assays are used to diagnose lymphoproliferative disorders and are used to search

for specific chromosomal abnormalities in the DNA of interphase cells.

10. C, page 840. Box 21-4

Suspicion for POEMS should be raised in the setting of thrombocytosis and sclerotic

bone lesions on plain radiographs.



Chapter 22: Transplantation Immunity and Clinical Applications

Prepared by Monica Bhagat, MD, University of Pennsylvania, and Marissa Shams, MD,

Emory University

1. Which of the following types of immune cells are cytopathic and facilitate graft

rejection?

A. Th1 cells

B. Th17 cells

C. A and B

D. Treg cells

2. In solid organ transplantation, the degree of HLA compatibility is described in terms

of the number of mismatches at which of the following particular histocompatibility

antigens?

A. ABO antigens only

B. HLA-A, HLA-B, and HLA-DR antigens

C. HLA-DR, HLA-DQ, and HLA-DP antigens

D. HLA matching is no longer critical for solid organ transplantation

3. In hematopoietic stem cell transplantation (HSCT), which of the following sources of

stem cells is typically associated with slower engraftment?

A. Peripheral blood stem cells

B. Bone marrow

C. Umbilical cord of newborn babies

D. All of the above

4. Which of the following monoclonal antibodies are chimeric in nature and bind to the

IL-2 receptor on T cells?

A. Basiliximab

B. OKT3

C. Basiliximab and Daclizumab

D. Rituximab

5. Minor histocompatability antigens (mHA) are which of the following:

A. Immunogenic peptides from polymorphic exogenous cellular proteins

B. Incapable of triggering an immune reaction and are harmless

C. Known to play a role in GVHD

D. Known to induce a strong T cell response when multiple mHA mismatches are

present

E. A&B

F. C&D

6. True or False: For HSC (hematopoietic stem cell) Transplant; allele matching occurs

only at HLA-A, HLA-B, HLA-C.

7. The most reliable means of detection for acute rejection:

A. HLA typing with CDC (complement dependent lymphotoxicity)

B. Percutatenous needle biopsy of the graft

C. PRA (Percentage reactive to Antibody)

D. CBC with differential and lymphocyte enumeration

8. Which of the following individuals are most at risk for development of acute Graft-

Versus-Host Disease (GVHD)?

A. Recipients of HSC transplant

B.. Recipients of small bowel transplant

C.. Immune compromised patient reeiving non-irradiated blood transfusions

D. None of the above

E. All of the above

9. Mononuclear cell infiltration, fibrosis and scarring of parenchyma and associated

blood vessels is associated with:

A. Acute Rejection

B. Hyperacute Rejection

C. Delayed Rejection

D. Chronic Rejection

10. Matching a prospective patient in need of solid organ transplant with prospective

donor includes all of the following steps, EXCEPT:

A. Identification of patient’s HLA haplotypes via Complement-dependent

lymphocytoxicity (CDC) assay or commercially available HLA-typing trays using

purified B and T lymphocytes

B. Screening for potential HLA antibodies in the recipient’s serum directed toward any

of the donors HLA haplotype.

C. ABO typing and crossmatching of donor and recipient for detection and ABO

incompatibility.

D. Desensitization of a mismatch anti-HLA antibody present in recipient serum against

donor HLA haplotypes with plasmapharesis and IVIG

Answers

1. C, page 869, Fig 22-4

Organ engraftment is promoted by a balanced Treg/effector cell ratio preventing the

destructive effects of Th1, Th2, and Th17 cells that mediate graft rejection. Therapies aim

to promote the function of the immunosuppressive Treg cells post-transplantation.

2. B, pages 870-71

Histocompatibility antigens include the major blood group antigens, HLA antigens, and a

variety of minor histocompatibility antigens. For solid organ transplants, we focus on the

number of mismatches at HLA-A, HLA-B, and HLA-DR antigens ONLY (C, DQ, and

DP are ignored). So, overall this means a perfect match is called a “zero antigen

mismatch” and the opposite scenario is known as “six-antigen mismatch”. Also, although

modern treatments have made it possible to completely suppress the recipient’s system

(making HLA matching less critical), there is better outcomes in well-matched

transplants!

3. D, pages 875-876.

Umbilical cord source provides rapidly available stem cells and less chance of rejection

with transplantation due to immaturity of cells. The main disadvantage of utilizing this

source is lack of adequate cell dose for larger patients and slower engraftment.

4. C, pages 880-881. Both of these are chimeric mouse-human monoclonal antibodies

that bind to the IL-2 receptor on T cells, leading to saturation of the IL-2 receptors and

prevents T cell activation. OKT3 is specific for the T cell marker CD3 but may lead to

cytokine release storm and late post-transplant lymphoproliferative disorder. Rituximab is

a murine/human monoclonal antibody directed against CD20 antigen on the surface of

normal and malignant B lymphocytes.

5. F, page 872

mHA are immunogenic peptides from polymorphic endogenous cellular proteins. These

proteins are present in different allelic forms in different individuals. In the transplant

setting, individual mHA mismatches between donor and recipient trigger a weak immune

response. However, multiple mismatches can induce a strong T cell response.

6. FALSE page 872

For HSCT transplant, allele matching occurs at HLA-A, HLA-B, HLA-C, HLA-DRß1 &

HLA-DQß1. A perfect match for HSC transplant occurs with 10/10 alleles matching. In

comparison, Solid Organ Transplant allele matching occurs at HLA-A, HLA-B, HLA-DR

and a perfect match occurs with 6/6 alleles matching.

7. B, page 874

The risk of acute rejection of solid organ transplant is highest in the first 3 months after

transplantation and manifests as a sudden decline in graft function. The most reliable

method for diagnosis of acute rejection is percutaneous needle biopsy of the allograft.

Many factors may contribute to the development of acute rejection including; degree of

HLA-mismatch, retransplantation, reactive anti-HLA antibody, antibody specificity for

donor HLA antigens.

8. E, page 876

Although GVHD is most commonly a complication of HSC transplant, other groups are

at risk including recipients of small bowel transplant and any immune compromised

patient receiving non-irradiated blood transfusions. The primary targets of acute GVHD

are skin, liver and intestinal tract.

9. D, page 876

Chronic Rejection typically develops months to years after transplantation with gradual

loss of graft function. On histopath examination there is mononuclear infiltration with

both Bcells and Tcells. Examples include “Vanishing Bile Duct Syndrome” in the liver

transplant and “Bronchiolitis Obliterans” with lung transplant.

10. D, page 880

Many transplant centers have developed protocols to “temporarily desensitize” patients in

order to create a window of opportunity during which anti-HLA antibody titers are

reduced low enough where a transplant be undertaken without the risk of hyperacute

rejection. However, this procedure is usually reserved for patients previously sensitized

to HLA-antigens (via pregnancy, prior transplant or transfusion) requiring solid organ

transplantation with deteriorating clinical condition and no other suitable match.

Additionally, this procedure is not a component of the routine screening algorithm for

histocompatability testing.

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