Hypersensitivity

What occurs when **allergen** causes widespread activation of blood vessel–associated mast cells throughout the body?

a. desensitization

b. neutropenia

c. systemic anaphylaxis

d. a wheal-and-flare reaction

c

What facilitate(s) the degradation of extracellular matrix proteins during **IgE**-mediated **allergic reactions**?

a. metalloproteases

b. histamine

c. prostaglandins

d. TNF-α

a

Activated mast cells release the contents of their granules within what time frame after antigen cross-links their surface **IgE** molecules?

a. days

b. minutes

c. hours

d. seconds

d

Which of the following characteristics correctly describes **FcεRII** (CD23)?

a. It has very similar structure to FcεRI.

b. It binds to the same topographical site on IgE as FcεRI.

c. It functions exclusively as a cell-surface receptor.

d. It carries out a distinct function compared with FcεRI.

d

What is an overreaction of the **immune system** to innocuous environmental antigens called?

a. hypersensitivity reaction

b. anergy

c. autoimmune reaction

d. passive immunity

a

The therapeutic antibody omalizumab binds to the site on IgE that interacts with which of the following?

a. FcεRII

b. allergen

c. the B-cell co-receptor

d. FcεRI

d

In which way are eosinophils like mast cells?

a. They produce eotaxin in order to recruit eosinophils to sites of parasite infection.

b. They produce histamine after their receptors are cross-linked.

c. They use a staged approach to the release of toxins, cytokines, and inflammatory mediators.

d. They express FcεRI at all times.

c

Which of the following is NOT commonly associated with **type I hypersensitivity reactions**?

a. the gastrointestinal tract

b. blood vessels

c. the respiratory tract

d. the excretory system

e. connective tissue

d

Where in the body is the majority of **IgE** located?

a. on the surface of mast cells in the tissues

b. in the lumen of the gastrointestinal tract as soluble molecules

c. in the blood as soluble molecules

d. on the surface of basophils in the blood

a

The β-lactam ring is required for the antimicrobial activity of penicillin. It may provoke allergic reactions in certain individuals by doing which of the following?

a. preferentially triggering TH1 responses in individuals susceptible to allergic reactions

b. binding to and cross-linking FcεRI on mast cells

c. causing the production of covalent conjugates with self proteins

d. causing the reversal of anaphylactoid reactions

c

Skin testing for allergic responsiveness involves injecting **allergen** into the dermis, which provokes what type of **inflammatory response**?

a. rhinitis

b. wheal-and-flare

c. delayed-type

d. systemic anaphylaxis

b

Although allergic disease is attributed to polymorphisms in different genes, perturbation of which of the following is an underlying commonality impacted by the combination of genetic variants?

a. the overall diversity of IgE molecules

b. the types of effector molecules contained in mast-cell cytoplasmic granules

c. the balance of TH1 and TH2 responses

d. the relative binding strengths of FcεRI and FcεRII

c

**Type I hypersensitivity reactions** are caused by what type of **allergens**?

a. polysaccharides

b. proteins

c. nucleic acids

d. lipids

b

What is administered to an individual experiencing anaphylactic shock in order to re-form tight junctions between endothelial cells, relax smooth muscle, and stimulate the heart?

a. leukotrienes

b. epinephrine

c. antivenom

d. penicillin

b

What is the major **allergen** in the house dust mite (*Dermatophagoides pteronyssimus*)?

a. a subunit of cytochrome *c* oxidase

b. troponin C

c. cystatin

d. a cysteine protease

d

Which of the following is a characteristic of the **FcεRI** receptor?

a. It binds to the Cε3 domain of IgE using its α chain.

b. It binds to IgE only when IgE is bound to antigen.

c. It is expressed as a dimer on the surfaces of mast cells, eosinophils, monocytes, smooth muscle cells, and platelets.

d. It interacts with IgE using disulfide bonds.

a

**Allergic rhinitis** occurs when inhaled **allergens** activate mast cells in the upper respiratory tract. In contrast, what occurs when mast cells in the lower airways are activated by inhaled **allergens**?

a. allergic conjunctivitis

b. allergic asthma

c. chronic asthma

d. anaphylactoid reactions

b

Which of the following does aspirin (acetyl salicylate) block to reduce **inflammation**?

a. release of histamine from activated mast cells

b. cyclooxygenase pathway

c. 5-lipoxygenase pathway

d. binding site of the H1 histamine receptor

b

Although both **FcεRI** and **FcεRII** bind to **IgE**, they cannot bind simultaneously to the same **IgE** molecule. If they were able to do so, what would be the consequence?

a. B cells would not be able to differentiate into IgE-secreting plasma cells.

b. ADAM10 would not be able to release FcεRII.

c. IgE would not be able to bind to antigen.

d. Soluble trimeric FcεRII could nonspecifically activate mast cells in the absence of antigen.

d

Which of the following describes a distinct manifestation of **chronic asthma** that does NOT apply to the **type I hypersensitivity reactions** associated with inhaled **allergens**?

a. occlusion of the airways with plugs of mucus

b. itchiness, tears, and inflammation

c. nasal discharge rich in eosinophils

d. shortness of breath and wheezing

a

Most eosinophils are found in which of the following?

a. the blood

b. the spleen

c. tissues

d. the bone marrow

c

What is the objective of using pharmacological agents in allergic disease?

a. to suppress the production of allergen-specific IgG

b. to deplete mast-cell populations in connective and mucosal tissues

c. to modify the allergen so that it is not recognized by the immune system

d. to minimize the impact of allergen

d

What is the genetic tendency of some individuals to mount an allergic response against harmless environmental substances called?

a. anergy

b. atopy

c. acute rejection

d. alloreactivity

b

Which of the following is true of individuals with **eosinophilia**?

a. They lack the capacity to produce eosinophil-derived inflammatory mediators.

b. They are more susceptible to heart failure and neuropathy.

c. They have eosinophil levels that are lower than normal.

d. They are unable to respond to helminth infections.

b

Which of the following are NOT expressed by mast cells on their cell surfaces?

a. Fc receptors for IgEFc receptors for IgA

b. Fc receptors for IgG

c. Fc receptors for IgM

d. Toll-like receptors

c

Mepolizumab is a **humanized monoclonal antibody** that shows promise as a pharmacological modulator of allergic responses. What **cytokine** does it target and block?

a. IL-5

b. IFN-γ

c. TGF-β

d. TNF-α

a

Which of the following is an immunological approach to treating allergic disease that involves exposing allergic individuals to **allergen** with the aim of modulating the immune response?

a. immunosuppression

b. vaccination

c. passive transfer of immunity

d. desensitization

d

In the context of binding to antigen on the cell surface, why are mast cells more versatile than **B cells**?

a. Mast cells are short lived, and this turnover allows constant adjusting of what IgE molecules are displayed.

b. FcεRI polymorphisms exceed the number of IgE antibody variants.

c. A mast cell arms itself with a variety of IgEs, whereas B cells express a single type of IgE molecule.

d. Mast cells constitutively express a much greater number of MHC class II molecules than B cells and can more effectively stimulate TH2 cells.

c

Poison ivy is an **allergen** associated with what type of hypersensitivity reaction?

a. type I

b. type II

c. type III

d. type IV

d

Choose the answer that best describes the affinity of the interaction between **IgE** and **FcεRI** compared to that of other **antibody** isotypes and their Fc receptors.

a. about the same

b. weaker than

stronger than

c

The nasal discharge in **allergic rhinitis** contains abundant numbers of which of the following?

a. neutrophils

b. plasma cells

c. eosinophils

d. mast cells

c

Genetic susceptibility to asthma is often associated with which of the following?

a. the production and function of antigen-specific IgE

b. high-affinity variants of FcεRII

c. the proteolytic cleavage of allergens in endosomes

d. a family history of smoking

a

Which of the following describes the part of a **type I hypersensitivity reaction** that occurs more than 6 hours after contact with **allergen**?

a. late-phase

b. chronic

c. edematous

d. delayed-type hypersensitivity

a

Unlike other **cytokines**, which **cytokine** is stored in the granules of mast cells and participates immediately upon the induction of an **IgE**-mediated allergic response?

a. IL-12

b. IL-1β

c. IL-6

d. TNF-α

d

What do **urticaria**, **angioedema**, and **eczema** have in common?

a. They are all caused by allergic reactions in the skin.

b. They are all a result of the loss of structural integrity of the stratum corneum.

c. They are all classified as type IV hypersensitivity reactions.

d. They are all provoked by an allergic response to inhaled allergens.

a

Which of the following function(s) in a manner similar to **histamine**, but with a biological activity that is more than 100 times more potent on a molecule-for-molecule basis?

a. chymotryptase

b. leukotrienes

c. prostaglandins

d. heparin

b

The eicosanoids include prostaglandins and leukotrienes. From which precursor are these derived?

a. fat-soluble vitamin

b. matrix protein

c. histamine

d. arachidonic acid

d

Where do **allergens** that cause **allergic rhinitis** enter the body?

a. gastrointestinal tract

b. skin

c. respiratory tract

d. blood stream

c

On what basis are the two types of human mast cells distinguished from each other?

a. the protease they secrete

b. their location

c. their expression of FcεRI

d. their reliance on T cells for differentiation

e. their release of histamine

f. the presence of storage granules

a, b, d

Anaphylactic shock occurs because of which of the following events?

a. Smooth muscle constriction occurs throughout the body.

b. Vascular permeability causes loss of fluid in the blood.

c. Disseminated intravascular coagulation (DIC) cuts off the normal blood supply to vital organs.

d. Intravascular hemolysis compromises the oxygen-carrying capacity of erythrocytes.

a, b

Prevention of allergic disease is accomplished by which of the following?

a. implementing behavioral changes to avoid contact with allergen

b. using epinephrine as an immunosuppressant

c. effecting environmental changes to eliminate the source of allergen

d. eradicating parasites from the body

a, c

Which of the following are not features of inhaled allergens that provoke type I hypersensitivity responses?

a. low dose

b. high solubility

c. high stability

d. high molecular mass

d

Mast cells reside in which of the following?

Correct Answer(s)

a. vascularized tissues

b. secondary lymphoid tissues

c. the bone marrow

d. mucosal and epithelial tissues

a, d

Which of the following occur when histamine binds to the H1 histamine receptor on cells in a tissue that is exposed to an allergen?

a. increased mucus secretion

b. increased vascular permeability

c. complement activation

d. airway constriction

e. immune-complex deposition

f. T cell–mediated cytotoxicity

a, b, d

Which of the following statements are correct regarding delayed-type hypersensitivity reactions?

a. Delayed-type hypersensitivity reactions are mediated by T cells.

b. Delayed-type hypersensitivity reactions become apparent 1–3 days after exposure to antigen.

c. Delayed-type hypersensitivity reactions require IgE bound to FcεRI on mast cells.

d. Activation of the delayed-type hypersensitivity response does not require antigen-presenting cells.

a, b

What do mast cells do when they are activated through FcεRI?

a. They release effector molecules by degranulation.

b. They secrete growth factors.

c. They secrete cytokines.

d. They synthesize eicosanoids.

a, d

Which of the following function(s) in a manner similar to histamine, but with a biological activity that is more than 100 times more potent on a molecule-for-molecule basis?

a)       heparin

b)      prostaglandins

c)       chymotryptase

d)      leukotrienes

d

Which of the following dyes is used to stain basophils?

a)       peroxidase

b)      eosin

c)       major basic protein

d)      hematoxylin

d

Activated mast cells release the contents of their granules within what time frame after antigen cross-links their surface IgE molecules?

a)       days

b)      minutes

c)       hours

d)      seconds

d

Unlike other cytokines, which cytokine is stored in the granules of mast cells and participates immediately upon the induction of an IgE-mediated allergic response?

a)       IL-12

b)      IL-6

c)       IL-1β

d)      TNF-α

d

Choose the answer that best describes the affinity of the interaction between IgE and FcεRI compared to that of other antibody isotypes and their Fc receptors.

\
a)       weaker than

b)      about the same

c)       stronger than

c

Which of the following are NOT expressed by mast cells on their cell surfaces?

a)       Toll-like receptors

b)      Fc receptors for IgG

c)       Fc receptors for IgE

d)      Fc receptors for IgA

e)      Fc receptors for IgM

e

Antibody isotype that you would expect to have the highest binding affinity for its antigen.

IgE 12 somatic mutations in heavy-chain V region

IgG3 18 somatic mutations in heavy-chain V region

IgG1 21 somatic mutations in heavy-chain V region

IgG2 22 somatic mutations in heavy-chain V region

IgG4 27 somatic mutations in heavy-chain V region

IgG4

Which of the following does aspirin (acetyl salicylate) block to reduce inflammation?

a)       5-lipoxygenase pathway

b)      cyclooxygenase pathway

c)       binding site of the H1 histamine receptor

d)      release of histamine from activated mast cells

b

Poison ivy is an allergen associated with what type of hypersensitivity reaction?

a)       type I

b)      type II

c)       type III

d)      type IV

d

Because basophils secrete IL-4 and IL-13 early during an adaptive immune response, they are believed to be important initiators of what type of response?

a)       TH2-cell

b)      Treg-cell

c)       cytotoxic T-cell

d)      TH1-cell

a

Which of the following is true of individuals with eosinophilia?

a)       They have eosinophil levels that are lower than normal.

b)      They lack the capacity to produce eosinophil-derived inflammatory mediators.

c)       They are more susceptible to heart failure and neuropathy.

d)      They are unable to respond to helminth infections.

c

In the context of binding to antigen on the cell surface, why are mast cells more versatile than B cells?

a)       Mast cells constitutively express a much greater number of MHC class II molecules than B cells and can more effectively stimulate TH2 cells.

b)      FcεRI polymorphisms exceed the number of IgE antibody variants.

c)       Mast cells are short lived, and this turnover allows constant adjusting of what IgE molecules are displayed.

d)      A mast cell arms itself with a variety of IgEs, whereas B cells express a single type of IgE molecule.

d

Which of the following occur when histamine binds to the H1 histamine receptor on cells in a tissue that is exposed to an allergen?

a)       airway constriction

b)      increased mucus secretion

c)       increased vascular permeability

d)      T cell–mediated cytotoxicity

e)       complement activation

f)       immune-complex deposition

a, b, c

What is an overreaction of the immune system to innocuous environmental antigens called?

a)       hypersensitivity reaction

b)      passive immunity

c)       autoimmune reaction

d)      anergy

a

What facilitate(s) the degradation of extracellular matrix proteins during IgE-mediated allergic reactions?

a)       metalloproteases

b)      prostaglandins

c)       TNF-α

d)      Histamine

a

Isotype switching to IgE and IgG3 is driven not only by the cytokines that basophils secrete, but also by what other molecule expressed by basophils?

a)       CD40 ligand

b)      FcεRI

c)       CD40

d)      TGF-β

a

What do mast cells do when they are activated through FcεRI?

a)They release effector molecules by degranulation.

b)They secrete growth factors.

c)They synthesize eicosanoids.

d)They secrete cytokines.

 

a, c

What is the genetic tendency of some individuals to mount an allergic response against harmless environmental substances called?

a)       alloreactivity

b)      acute rejection

c)       anergy

d)      atopy

d

Basophils contain secretory granules that contain a set of effector molecules that are similar to those of what other cell type?

a)       cytotoxic T cells

b)      eosinophils

c)       mast cells

d)      neutrophils

c

Although both FcεRI and FcεRII bind to IgE, they cannot bind simultaneously to the same IgE molecule. If they were able to do so, what would be the consequence?

a)       Soluble trimeric FcεRII could nonspecifically activate mast cells in the absence of antigen.

b)      IgE would not be able to bind to antigen.

c)       B cells would not be able to differentiate into IgE-secreting plasma cells.

d)      ADAM10 would not be able to release FcεRII.

a

Which of the following statements are correct regarding delayed-type hypersensitivity reactions?

a) Delayed-type hypersensitivity reactions are mediated by T cells.

b) Delayed-type hypersensitivity reactions require IgE bound to FcεRI on mast cells.

c) Activation of the delayed-type hypersensitivity response does not require antigen-presenting cells.

d) Delayed-type hypersensitivity reactions become apparent 1–3 days after exposure to antigen.

a, d

Which of the following describes the part of a type I hypersensitivity reaction that occurs more than 6 hours after contact with allergen?

a)       edematous

b)      late-phase

c)       chronic

d)      delayed-type hypersensitivity

b

Which of the following is a characteristic of the FcεRI receptor?

a)       It is expressed as a dimer on the surfaces of mast cells, eosinophils, monocytes, smooth muscle cells, and platelets.

b)      It binds to the Cε3 domain of IgE using its α chain.

c)       It binds to IgE only when IgE is bound to antigen.

d)      It interacts with IgE using disulfide bonds.

b

Skin testing for allergic responsiveness involves injecting allergen into the dermis, which provokes what type of inflammatory response?

a)       rhinitis

b)      wheal-and-flare

c)       systemic anaphylaxis

d)      delayed-type

b

On what basis are the two types of human mast cells distinguished from each other?

a) the protease they secrete

b) the presence of storage granules

c) their expression of FcεRI

d) their location

e) their reliance on T cells for differentiation

f) their release of histamine

a, d, e

Which of the following is NOT commonly associated with type I hypersensitivity reactions?

a)       blood vessels

b)      the respiratory tract

c)       connective tissue

d)      the excretory system

e)      the gastrointestinal tract

d

In which way are eosinophils like mast cells?

a)       They use a staged approach to the release of toxins, cytokines, and inflammatory mediators.

b)      They produce histamine after their receptors are cross-linked.

c)       They produce eotaxin in order to recruit eosinophils to sites of parasite infection.

d)      They express FcεRI at all times.

a

Most eosinophils are found in which of the following?

a)       the spleen

b)      the bone marrow

c)       tissues

d)      the blood

c

Where in the body is the majority of IgE located?

a)       on the surface of basophils in the blood

b)      in the lumen of the gastrointestinal tract as soluble molecules

c)       on the surface of mast cells in the tissues

d)      in the blood as soluble molecules

c

The eicosanoids include prostaglandins and leukotrienes. From which precursor are these derived?

a)       fat-soluble vitamin

b)      arachidonic acid

c)       histamine

d)      matrix protein

b

What explains the relatively recent emergence of widespread allergic disease in developed countries in which residents experience reduced exposure to parasite infections?

a)       immunosuppressive drugs

b)      IgE mutations

c)       the hygiene hypothesis

d)      IgM to IgE switching

c

Which of the following are correct regarding multicellular parasites that infect humans?

a) They are recognized by IgE antibodies that protect the body against their invasion.

b) They always multiply in the human body like any other pathogen.

c) They are highly immunogenic because they are biologically and chemically distinct from human cells.

d) They are dislodged from human tissues by explosive inflammatory reactions.

e) They are readily phagocytosed by human macrophages and neutrophils.

 

 

a, d

The therapeutic antibody omalizumab binds to the site on IgE that interacts with which of the following?

a)       FcεRI

b)      FcεRII

c)       the B-cell co-receptor

d)      allergen

a

Place the following IgG isotopes in order according to when they switch during a germinal-center reaction.

IgG1

IgG2

IgG3

IgG4

IgG3, IgG1, IgG2, IgG4

Which of the following statements are correct in reference to individuals in tropical countries who are persistently infected with helminths?

a) Only a small proportion of the IgE molecules made in response to helminth infection are actually parasite-specific.

b) The effector molecules made by the immune system in response to helminths only act on the pathogen itself.

c) Parasite infection predisposes them to type I hypersensitivity reactions.

d) The immune response to helminths in such individuals induces CD4 TH2 cells.

e) They have elevated numbers of mast cells and eosinophils compared with uninfected individuals.

\

a, d, e

What is Hypersensitivity?

An exaggerated or inappropriate immune response to an antigen/immunogen, causing tissue damage

Pattern recognition receptors (PRRs) in hypersensitivity

overexpression or polymorphism of certain types

PRR

class of receptors that can directly recognize the specific molecular structures on the surface of pathogens, apoptotic host cells, and damaged senescent cells.

Which hypersensitivity reaction is immediate?

Type I

Which hypersensitivity reaction is cytotoxic?

Type II

Which hypersensitivity reaction is complex mediated?

Type III

Which hypersensitivity reaction is delayed?

Type IV

Which hypersensitivity reaction has an IgE mediator?

Type I

Which hypersensitivity reaction has an IgG and IgM antibody mediator?

Type II and III

Which hypersensitivity reaction has T lymphocytes and macrophage mediators?

Type IV

What are hay fever and allergic asthma an example of?

Type I

What is farmers lung an example of?

Type III

What is transfusion reaction an example of?

Type II

What is contact dermatitis an example of?

Type IV

How is Type I hypersensitivity induced?

Allergen induces cross-linking of IgE bound to mast cells and basophils = release of vasoactive mediators

Typical manifestations of type I

* systemic anaphylaxis
* local anaphylaxis
* hay fever
* asthma
* hives
* food allergies
* eczema

How is cytotoxic type II hypersensitivity induced?

Antibodies directed against cell surface antigens mediates cell destruction via complement or ADCC

Which hypersensitivity reaction uses ADCC?

Type II

Typical manifestations of type II

* transfusion reactions
* erythroblastosis fetalis
* AIHA