Question 1

Which one of the following statements concerning autoimmune disease is true?
A)Autoimmunity manifests as organ-specific,not systemic,disease.
B)Infectious microorganisms are frequently present in autoimmune lesions.
C)Effector mechanisms in autoimmunity include circulating autoantibodies,immune complexes,and autoreactive T lymphocytes.
D)Among the genes associated with autoimmunity,associations are particularly prevalent with class I MHC genes.
E)Many autoimmune diseases show higher incidence in males than in females.

Accepted Answer

Various effector mechanisms are responsible for tissue injury in different autoimmune diseases.These include circulating autoantibodies,immune complexes,and autoreactive T lymphocytes.Autoimmune diseases may be either systemic (i.e. ,systemic lupus erythematosus)or organ specific (i.e. ,type 1 diabetes mellitus,multiple sclerosis).Among the genes associated with autoimmunity,the strongest associations are with MHC genes and usually with class II MHC genes (ankylosing spondylitis is an exception).In most cases of autoimmunity,infectious microorganisms are neither present in lesions nor detectable in patients when autoimmunity develops;this suggests that lesions in autoimmunity result not from the infectious agent directly but from host immune responses that may be triggered by microbes.Finally,many autoimmune diseases show higher incidence in females than in males,although the reasons for this are not well understood.

Question 2

Which of the following is NOT associated with increased relative risk of developing systemic lupus erythematosus?
A)Female gender
B)Deficiency in complement protein C2
C)African-American ethnicity
D)Presence of HLA-DR3
E)Defect in B cell maturation

Accepted Answer

Systemic lupus erythematosus (SLE)is a chronic,remitting and relapsing,multisystem disease that affects predominantly women,with an incidence of 1 in 700 in women between the ages of 20 and 60 years.Incidence increases to about 1 in 250 in African-American women.The female-to-male ratio is 10:1.Deficiencies of classical complement proteins,especially C2 or C4,are seen in about 10% of patients with SLE;abnormal complement levels may result in defective clearance of immune complexes.Individuals with the class II DR2 or DR3 HLA allele have a five-fold higher probability of developing SLE.In contrast,patients with defects in B cell maturation would typically have impaired antibody synthesis;thus it is unlikely that these patients would develop an autoimmune disease characterized by the production of autoantibodies.

Question 3

Experimental autoimmune encephalomyelitis (EAE)is a mouse model of a human organ-specific autoimmune disease mediated by T lymphocytes.In EAE,rodents are immunized with proteins found in the myelin sheath of central nervous system neurons.EAE is a model for which of the following human diseases?
A)Rheumatoid arthritis
B)Autoimmune myocarditis
C)Systemic lupus erythematosus
D)Diabetes mellitus type 1 (insulin-dependent)
E)Multiple sclerosis

Accepted Answer

Experimental autoimmune encephalomyelitis (EAE)is an animal model for multiple sclerosis,a central nervous system (CNS)demyelinating disease with an autoimmune etiology.EAE is induced by immunizing mice with antigens normally present in CNS myelin,in conjunction with adjuvant,which is necessary to stimulate the innate immune system.One to 2 weeks after immunization,animals develop an encephalomyelitis,characterized by perivascular infiltrates composed of lymphocytes and macrophages in the CNS white matter,followed by demyelination.Neurologic lesions can be mild and self-limited or chronic and relapsing,depending on the animal species and strain and antigen-adjuvant preparation used.

Question 4

Which type of hypersensitivity disease is caused by deposition of antigen-antibody complexes in blood vessel walls?
A)Type I
B)Type II
C)Type III
D)Type IV
E)Type V

Accepted Answer

Hypersensitivity diseases are often categorized by numerical designation.Type III is immune complex disease.Type I is immediate hypersensitivity (allergic)disease.Type II is disease caused by antibodies binding to antigens in tissues.Type IV is T cell-mediated disease.There is no type V hypersensitivity.

Question 5

Individuals with the class I HLA-B27 allele have a 90-fold greater chance of developing which of the following inflammatory diseases,relative to HLA-B27-negative individuals?
A)Rheumatoid arthritis
B)Ankylosing spondylitis
C)Pemphigus vulgaris
D)Diabetes mellitus type 1 (insulin dependent)
E)Multiple sclerosis

Accepted Answer

Individuals who are positive for the class I HLA-B27 allele have a 90- to 100-fold greater chance of developing ankylosing spondylitis than do individuals lacking B27.This constitutes the strongest HLA disease association thus far described.Ankylosing spondylitis is an autoimmune disease affecting vertebral joints.Rheumatoid arthritis,pemphigus vulgaris,diabetes mellitus,and multiple sclerosis are more likely to develop in individuals with certain class II MHC alleles,but these carry much lower relative risks (between 4 and 25).

Question 6

Which of the following would NOT be a likely therapy for treating autoimmune diseases?
A)Corticosteroids
B)Small molecule inhibitor of VLA-4
C)Cyclosporine
D)CTLA-4 antagonist
E)Plasmapheresis

Accepted Answer

The mainstay therapy for hypersensitivity diseases is anti-inflammatory drugs,particularly corticosteroids.In contrast,blocking CTLA-4,a negative regulator of T cell responses,is likely to exacerbate preexisting conditions of hypersensitivity.(The CTLA-4 knockout mouse displays a lymphoproliferative phenotype. )An inhibitor of VLA-4 would be effective in blocking leukocyte transmigration into tissues,thus exerting an anti-inflammatory effect.Cyclosporine is a potent immunosuppressive drug used to block T cell activation.Plasmapheresis has been used during exacerbations of antibody-mediated diseases to reduce circulating levels of antibodies or immune complexes.

Question 7

A 14-year-old boy is brought to the pediatrician's office in mid summer because of an itchy,blistering rash on his calves and forearms.The rash developed 24 hours after he returned from a weekend Boy Scout camping trip.The pediatrician suspects the lesion is caused by poison ivy.If the doctor is correct,which one of the following is NOT a prominent component in the immunologic mechanisms causing the skin lesions?
A)T cells
B)IgE-coated mast cells
C)Interferon-F1F1F1S1F1F1F10
D)Endothelial adhesion molecules
E)Chemokines

Accepted Answer

Poison ivy rash is a form of contact dermatitis in which there is a delayed-type hypersensitivity (DTH)reaction.The patient's vesicular dermatitis was evoked by his repeated exposure to urushiol,the antigenic component of poison ivy.Endothelial adhesion molecules and chemokines mediate the recruitment of previously sensitized CD4⁺ T cells of the T_H1 subset and CD8⁺ T cells,which secrete cytokines such as interferon-F1F1F1S1F1F1F10 and activate macropha-ges.Activated macrophages release enzymes and reactive oxygen intermediates that damage cellular tissue.IgE-coated mast cells are involved in immediate hypersensitivity reactions,not DTH reactions.

Question 8

An 8-year-old boy from the intermountain region of the United States is brought to the pediatrician with fever,rash,and pain in his knees and ankles.Pericarditis is evident on auscultation,and echocardiography confirms mitral valve regurgitation.Three weeks before this episode,the patient had experienced a sore throat but had not received medical attention.High titers of antistreptococcal antibodies are present in the serum.This child's disease is a result of which one of the following phenomena?
A)Clonal anergy
B)Peripheral tolerance
C)Epitope spreading
D)Central tolerance
E)Molecular mimicry

Accepted Answer

This boy has acute rheumatic fever (ARF),which is caused by an immune response initially specific for streptococcal antigens,but that cross-reacts with heart antigens.Molecular mimicry refers to the postulated mechanism whereby immune responses to a microbe containing antigens that cross-react with self antigens may trigger an autoimmune response.This autoimmune response may then persist,even in the absence of the inciting microbe.In ARF,antistreptococcal antibodies cross-react with myocardial proteins.Molecular sequencing has revealed numerous short stretches of homologies between streptococcal protein and myocardial proteins.The incidence of ARF has declined dramatically in the United States because of widespread use of antibiotics in the treatment of streptococcal infections before antibody responses can fully develop.Clonal anergy,peripheral tolerance,and central tolerance are mechanisms that would prevent immune responses to self antigens,and thus do not explain this patient's disease.Epitope spreading occurs when autoimmune reactions develop against several different epitopes of self-molecules during the evolution of an autoimmune disease;these epitopes are different from the initial targets of autoreactive lymphocytes at the outset of the disease.Epitope spreading is due to the release of self antigens from damaged tissue and from activation of tissue-based antigen-presenting cells by the local inflammatory response.

Question 9

Which of the following is a common cause of hypersensitivity diseases?
A)Failure of lymphocyte maturation
B)Treatment with corticosteroids
C)Disseminated cancer
D)Failure of self-tolerance
E)Malnutrition

Accepted Answer

Hypersensitivity diseases are caused by immune responses.A common underlying condition leading to hypersensitivity diseases is failure of self-tolerance,with subsequent immune responses directed against self antigens (autoimmune diseases).Hypersensitivity diseases may also result from uncontrolled or excessive responses against foreign antigens,including microbes and environmental substances.Failure of lymphocyte maturation,corticosteroid therapy,and malnutrition are associated with immunodeficiency.

Question 10

All of the following are effector mechanisms of antibody-mediated disease EXCEPT:
A)Opsonization and phagocytosis of cells
B)Fas-dependent apoptosis of cells
C)Complement- and Fc receptor-mediated inflammation and tissue injury
D)Antibody stimulation of cell surface receptors in the absence of the physiologic ligands
E)FcF1F1F1S1F1F1F10R crosslinking

Accepted Answer

Fas-dependent apoptosis is a regulatory mechanism in T cell-mediated responses and may be involved in T cell-mediated damage to other cells,but the Fas pathway is not stimulated by antibodies.Antibody-mediated (types I to III)hypersensitivity diseases involve four main effector mechanisms: (1)IgE coats mast cells and links the presence of allergens with mast cell activation and release of inflammatory mediators;(2)antibody-mediated opsonization of cells and activation of complement promotes phagocytosis of cells through phagocyte Fc or C3 receptors;(3)antibody binding to tissues can promote recruitment of leukocytes via binding to Fc receptors on leukocytes or by activation of complement with release of chemotactic byproducts;and (4)autoantibodies specific for cell surface receptors either stimulate receptor activity in the absence of the physiologic ligand or inhibit binding of physiologic ligands to their receptors.

Question 11

In which of the following disorders is the underlying pathogenic mechanism NOT due to antibody-mediated damage to cells or tissues?
A)Pernicious anemia
B)Autoimmune hemolytic anemia
C)Pemphigus vulgaris
D)Acute rheumatic fever
E)Hyperacute allograft rejection

Accepted Answer

Pernicious anemia is caused by neutralizing autoantibodies specific for intrinsic factor,which is a secreted protein required for absorption of vitamin B₁₂ in the gastrointestinal tract.The lack of vitamin B₁₂ absorption leads to decreased erythropoiesis,with subsequent anemia.Autoimmune hemolytic anemia is caused by opsonizing antibodies specific for erythrocyte membrane antigens,leading to their destruction by phagocytes.Pemphigus vulgaris occurs when autoantibodies specific for epidermal cell intracellular junctions cause inflammatory disruption of the skin,leading to formation of skin vesicles.Acute rheumatic fever is caused by antistreptococcal cell wall antibodies that cross-react with myocardial antigens,leading to inflammation and damage to myocardium.Hyperacute allograft rejection is caused by antibodies specific for alloantigens on graft endothelial cells,leading to blood vessel wall damage and thrombosis.

Question 12

Which of the following statements about immune complex-mediated diseases is NOT true?
A)Immune complexes may contain antibodies bound to either self or foreign antigens.
B)Immune complex-mediated diseases generally show systemic manifestations.
C)Pathologic features of immune complex diseases are determined by the cellular source of the antigen.
D)Small complexes are deposited in vessels more than large complexes,which are usually efficiently phagocytoseD.
E)Complexes containing cationic antigens are more likely to produce severe,long-lasting injury by depositing in blood vessels and renal glomeruli.

Accepted Answer

A hallmark of immune complex-mediated disease is that pathologic features reflect the site of immune complex deposition and are not determined by the cellular source of the antigen.As such,immune complex-mediated diseases tend to be systemic,with little or no specificity for particular tissues.Immune complexes that cause disease may be composed of either self antigens or foreign antigens with bound antibodies.These complexes are produced during normal immune responses,but they cause disease only when they are produced in excessive amounts or are not efficiently cleared so that they become deposited in tissues.Small complexes are often not phagocytosed and tend to be deposited in vessels more readily than large complexes,which are usually cleared by phagocytes.Complexes containing cationic antigens bind tightly to negatively charged components of basement membranes of blood vessels and kidney glomeruli,typically producing long-lasting injury.

Question 13

A 26-year-old African-American woman visits her physician because of a prominent rash over her nose and cheeks,which she first noticed following her return from a vacation in Jamaica.She also complains of fever,fatigue,weight loss,and joint pain over the last several months.Serologic tests are conclusive for systemic lupus erythematosus (SLE),an autoimmune disease that can manifest clinically with rashes,arthritis,glomerulonephritis,hemolytic anemia,thrombocytopenia (low platelet count),and central nervous system involvement.The principal diagnostic test result specific for this condition is a high titer of autoantibodies against which of the following?
A)Glomerular basement membrane
B)Rh blood group antigen
C)Myelin
D)Double-stranded DNA
E)IgG

Accepted Answer

The most specific diagnostic test for systemic lupus erythematosus (SLE)is the detection of antibodies against double-stranded DNA.Nevertheless,many different autoantibodies are found in patients with SLE,including other "antinuclear" antibodies.These include autoantibodies against ribonucleoproteins,histones,and nucleolar antigens.Other autoantibodies found in SLE bind erythrocytes and platelets.Antibodies specific for the glomerular basement membrane are typical of Goodpasture's syndrome,and anti-IgG antibodies,called "rheumatoid factor," are found in several autoimmune diseases,including rheumatoid arthritis.

Question 14

Which of the following conditions is NOT associated with immune complex deposition?
A)Arthus reaction
B)Autoimmune hemolytic anemia
C)Serum sickness
D)Systemic lupus erythematosus
E)Poststreptococcal glomerulonephritis

Accepted Answer

Autoimmune hemolytic anemia is a type II hypersensitivity disease caused by autoantibodies against erythrocyte membrane proteins,such as Rh blood group antigens.Antibody-mediated opsonization and phagocytosis of erythrocytes leads to hemolysis and subsequent anemia.All other choices listed (poststreptococcal glomerulonephritis,the Arthus reaction,serum sickness,and systemic lupus erythematosus)are examples of immune complex-mediated,or type III hypersensitivity,diseases.

Quiz 12: Hypersensitivity

Which one of the following statements concerning autoimmune disease is true?

Which of the following is NOT associated with increased relative risk of developing systemic lupus erythematosus?

Experimental autoimmune encephalomyelitis (EAE) is a mouse model of a human organ-specific autoimmune disease mediated by T lymphocytes.In EAE,rodents are immunized with proteins found in the myelin sheath of central nervous system neurons.EAE is a model for which of the following human diseases?

Which type of hypersensitivity disease is caused by deposition of antigen-antibody complexes in blood vessel walls?

Individuals with the class I HLA-B27 allele have a 90-fold greater chance of developing which of the following inflammatory diseases,relative to HLA-B27-negative individuals?

Which of the following would NOT be a likely therapy for treating autoimmune diseases?

Which of the following is a common cause of hypersensitivity diseases?

All of the following are effector mechanisms of antibody-mediated disease EXCEPT:

In which of the following disorders is the underlying pathogenic mechanism NOT due to antibody-mediated damage to cells or tissues?

Which of the following statements about immune complex-mediated diseases is NOT true?

Which of the following conditions is NOT associated with immune complex deposition?