Hypersensitivity disorders

Question 1

Which one of the following is a type 2 cytokine?

a. NF-kB
b. TNF
c. IL-13
d. IFN-gamma
e. IL-2

Answer 1

c. IL-13
Type-1 cytokines are cytokines produced by Th1 T-helper cells while Type-2 cytokines are those produced by Th2 T-helper cells. Type-1 cytokines include IL-2 (IL2), IFN-gamma (IFN-G), IL-12 (IL12) & TNF-beta (TNF-b), while Type 2 cytokines include IL-4 (IL4), IL-5 (IL5), IL-6 (IL6), IL-10(IL10), and IL-13 (IL13).

Question 2

What is an allergen?

a. a substance that is used to combat the allergic reactions
b. a substance that elicits the immediate hypersensitivity reaction

Answer 2

b. a substance that elicits the immediate hypersensitivity reaction

Question 3

What is the frequency of allergic disorders in Europe and the US?

a. 40%
b. 15%
c. 60%
d. 9%
e. 20%

Answer 3

e. 20%

Question 4

Which cytokine induces the production of IgE?

a. IL-6
b. TNF
c. IFN-alpha
d. IL-4
e. IL-13

Answer 4

d. IL-4 and e. IL-13

these 2 cytokines including IL-5 induce the switching to the E chain and thus the production of IgE

Question 5

What is sensitization?

Answer 5

The typical sequence of events in immediate hypersensitivity consists of exposure to an antigen, activation of TH2 cells and B cells specific for the antigen, production of IgE antibody, binding of the antibody to Fc receptors of mast cells, and triggering of the mast cells by re-exposure to the antigen, resulting in the release of mediators from the mast cells and the subsequent pathologic reaction. Binding of
IgE to mast cells is also called sensitization because
IgE-coated mast cells are ready to be activated on
antigen encounter.

Question 6

What are some of the common characteristics of the common allergens?

Answer 6

Low to medium molecular weight, stability, glycosylation, solubility in body fluids.

Question 7

How do polysaccharides elicit an immune response?

a. by getting converting into an SH3 molecule
b. directly inducing switching to IgE
c. getting split by an enzyme into smaller carbohydrate pieces and slipping through the membrane of the T cell
d. by attaching to a protein to become an allergen.

Answer 7

d. by attaching to a protein to become an allergen.
all non-protein compounds have to first attach themselves to a protein to elicit an immune response. Penicillin, a non-protein substance, can elicit a very strong influx in IgE production.

Question 8

How does penicillin elicit allergic reaction?

a. react with self-proteins to form hapten-carrier conjugates, that induce IL-4 production.
b. bind to the FceR1 receptor and promotes degranulation of the mast cells
c. penicillin can never elicit an immune response
d. after getting spliced by the serum enzymes, penicillin can act on the IgE genes and upregulate them

Answer 8

a. react with self-proteins to form hapten-carrier conjugates, that induce IL-4 production.

Question 9

Which cytokines are produced by the epithelia during the injury in hypersensitivity reactions?

a. NF-kB, filaggrin, IL-4
b. TNF, IFN-gamma
c. M-CSF, IL-21, IFN-alpha
d. IL-25, IL-33, TSLP

Answer 9

d. IL-25, IL-33, TSLP

Question 10

What is GATA3 gene responsible for?

Answer 10

GATA3 enhances secretion of IL-5 and IL-13

Question 11

What is the receptor allergens?

a. CD33
b. TLR-3
c. NLR-4
d. CD40
e. CD55

Answer 11

d. CD40

Question 12

What are the type 2 cytokine secreting cells?

Answer 12

Th2, ILC2s, mast cells, basophils, eosinophils

Question 13

Role of IL-4 in hypersensitivity

Answer 13

Induced expression of endothelial VCAM-1, which promotes the recruitment of eosinophils and additional Th2s.

Question 14

Role of IL-5 in hypersensitivity

Answer 14

Activation of eosinophils

Question 15

Role of IL-13 in hypersensitivity

Answer 15

Stimulates epithelial tissue (e.g. in the airways) to release more mucus.

Question 16

What do ILC2s primarily produce?

a. IL-5 and INF-gamma
b. G-CSF and IL-6
c. TNG-alpha and gamma
d. IL-5 and IL-13

Answer 16

d. IL-5 and IL-13

Question 17

What are the growth and differentiation factors for mast cells?

Answer 17

Stem cell factor, IL-3

Question 18

What is abundant in the mucosal tissue mast cells?

a. keratan sulfate
b. dermatan sulfate
c. heparan sulfate
d. chondroitin sulfate

Answer 18

d. chondroitin sulfate

tryptase is also abundant in the granules of the mucosal tissue mast cells.

Question 19

What is the life-span of mast cells?

a. hours
b. days
c. weeks
d. weeks to months
e. years
f. months to years

Answer 19

d. weeks to months

Question 20

What is the substance predominant in the connective tissue mast cells?

Answer 20

Connective tissue mast cells show little T cell dependence. In humans, the corresponding subset is identified by the presence of several neutral proteases in the granules, including tryptase, chymase, cathepsin G-like protease, and carboxypeptidase. They also have abundant heparin and produce large quantities of histamine.

Question 21

Which receptor binds the Stem cell factors on the mast cell precursor?

a. NOD-like receptor
b. Fce type 1 receptor
c. c-Kit receptor
d. MCD receptor

Answer 21

c. c-Kit receptor

Question 22

What is the life-span of basophils?

a. hours
b. days
c. weeks
d. weeks to months
e. years
f. months to years

Answer 22

b. days

Question 23

What are the growth and differentiation factors for basophils?

Answer 23

IL-3

Question 24

Which cells express Fc epsilon R1?

Answer 24

Mast cells. basophils, eosinophils, Langerhans cells, some dermal macrophages, activated monocytes

Question 25

What makes up Fc epsilon R1?

a. CD44, 2 zeta chains, TCL
b. alpha chain, beta chain, 2 gamma chains
c. alpha chain, 2 gamma chains
d. CD50, zeta chain, tyrosine-based chain

Answer 25

b. alpha chain, beta chain, 2 gamma chains, and c. alpha chain, 2 gamma chains, DEPENDING on the type of the cell. mast cells and basophils express tetramers, while eosinophils and several other cell types express trimers.

Question 26

How many ITAMs are on the Fc epsilon R1?

a. 2, both on gamma chains
b. 2, one on beta and one on gamma chain
c. 3, one on every gamma and beta chains
d. 4, 2 on the beta chain and one on each gamma chain
e. 6, 2 on each chain

Answer 26

c. 3, one on every gamma and beta chains
there is one ITAM (immunoreceptor tyrosine-based activation motif) on the beta chain in the cytoplasmic carboxy-terminal. 2 identical gamma chains are linked by a disulfide bond. The cytoplasmic portion of each gamma chain contains a single ITAM.

Question 27

What is the alpha chain responsible for in Fc epsilon R1?

Answer 27

Binding on IgE

Question 28

What are the beta and gamma chains responsible for in Fc epsilon R1?

Answer 28

They initiate signaling cascade needed for mast cell activation.

Question 29

What happens in Fc epsilon R1 alpha chain knockout mice?

Answer 29

They don’t develop anaphylaxis.

Question 30

Of the following, the single best defining description of a type IV hypersensitivity reaction is that it involves:

a.  allergen
b. antigen
c.  cytokine release
d. cutaneous manifestations
e. a delayed type of hypersensitivity

Answer 30

e. a delayed type of hypersensitivity
The other types of hypersensitivity reactions can occur immediately the antigen is encountered whereas type IV hypersensitivity, because it is T-cell mediated, usually takes several hours to manifest itself. This is because the T-cells need time to proliferate before there are a sufficient number of cells to cause symptoms. Although type IV hypersensitivity reactions may be caused by allergen (e.g., in contact dermatitis), this is not the single best defining feature. All immune responses involve antigen, not just type IV hypersensitivity reactions. Most types of immune response will involve the release of cytokines. While type IV hypersensitivity reactions often involve the skin, this is not the single best defining feature.

Question 31

The beta chain of the Fc epsilon RI:

a. binds IgE
b. is associated with Lyn
c. contains a GPI-anchor
d. possesses an ITIM sequence
e. is also used by FcϵRII

Answer 31

b. is associated with Lyn
The cytoplasmic domain of the β chain is linked to the Lyn protein tyrosine kinase which is involved in initiating the series of phosphorylation-induced activation steps ultimately leading to the release of the mast cell mediators. The α chain of the FcϵRI binds IgE. The α, β, and γ chains of FcϵRI all possess cytoplasmic domains and thus are held in the membrane by hydrophobic transmembrane sequences. The β chain, together with the γ chains, contain immunoreceptor tyrosine-based activation motifs (ITAM) in their cytoplamic domains, not inhibitory ITIM sequences. The low affinity IgE receptor comprises a trimer bearing C-type lectin domains.

Question 32

Which one of the following mast cell products is NOT preformed and therefore has to be newly synthesized?

a. histamine
b. prostaglandin D2
c. heparin
d. neutral protease
e. eosinophil chemotactic factor (ECF)

Answer 32

b. prostaglandin D2
Prostaglandins and thromboxanes are newly synthesized by the mast cell using the cyclo-oxygenase pathway. The leukotrienes B4, C4, and D4 (slow reacting substance of anaphylaxis, SRS-A) are also newly synthesized by the mast cell, in this instance using the lipoxygenase pathway. Histamine is preformed and stored in mast cell granules. Upon release it causes vasodilatation, increased capillary permeability, chemokinesis, and brochoconstriction. Heparin is preformed and stored in mast cell granules. Neutral protease is preformed and stored in mast cell granules. ECF is preformed and stored in mast cell granules.

Question 33

Lol p 1-11 are allergens cloned from:

a. rye grass pollen
b. house dust mite
c. house dust mite feces
e. animal dander
d. dermatophagoides pteryonyssinus

Answer 33

a. rye grass pollen
At least 10% of the population, to a greater or lesser degree, develop allergies involving localized IgE-mediated anaphylactic reactions to extrinsic allergens. An increasing number of these allergens have now been cloned including Der p 1-14 from house dust mites and Lo l p1-11 from rye grass pollen. The Der p allergens have been cloned from the house dust mite and shown to provoke asthma and eczema. The house dust mite is a major cause of allergic disease and its fecal pellets are the main source of the allergen. Animal danders can be responsible for provoking either asthma or eczema. Dermatophagoides pteryonyssinus is the house dust mite which is the source of the Der p 1-14 allergens.

Question 34

Type I hypersensitivity can be blocked using:

a. histamine
b. an anti-IgA monoclonal antibody
c. a monoclonal of mixed antibody class
d. sodium cromoglycate (cromolyn sodium)
e. IL-5

Answer 34

d. sodium cromoglycate (cromolyn sodium)
Sodium cromoglycate (cromolyn sodium) is a mast cell stabilizer which makes the cell resistant to triggering. It is thus able to block type I hypersensitivity.Histamine is a vasoactive amine released upon degranulation of mast cells and is responsible for many of the symptoms of type I hypersensitivity. The humanized monoclonal omalizumab is an IgG antibody directed against the FcϵRI-binding Cϵ3 domain of IgE and is used to treat severe forms of asthma. A monoclonal of mixed antibody class is a contradiction because a monoclonal antibody, and can only be of a single heavy and light chain class. IL-5 promotes eosinophilia.

Question 35

What is a major unresolved question concerning antibody-dependent cellular cytotoxicity (ADCC)?

a. whether antibody is involved
b. whether it can be carried out by NK cells
c. whether it leads to cell death
d. whether it is complement-dependent
e. to what extent it occurs in vivo

Answer 35

e. to what extent it occurs in vivo
This phenomenon is well established in vitro but it is difficult to establish how significant a role it has in vivo. ADCC is antibody-dependent cellular cytotoxicity (alternatively referred to as antibody-dependent cell-mediated cytotoxicity) and therefore, by definition, involves antibody. Specific IgG antibodies target the cytotoxicity by effector cells which have bound the antibody via cell surface Fcγ receptors. ADCC can be carried out by a number of Fcγ receptor-bearing cell types including monocytes, macrophages, neutrophils, and NK cells. ADCC is antibody-dependent cellular cytotoxicity and therefore, by definition, leads to the death of the target cell. ADCC is dependent on antibody but not on complement although bound C3 can enhance the reaction if the effector cells bear C3b receptors.

Question 36

Name one genetic factor that determines whether an individual can make an immune response to a specific allergen

Answer 36

The individual’s MHC haplotypes determine which antigens and antigen fragments are presented to the T cells.

Question 37

In which tissue does Th2 response predominate, and in which tissue does Th1 response predominate?

Answer 37

Th2 predominates in mucosal tissues, whereas Th1 responses predominate in the skin and CNS

Question 38

Give an example of a mediator that can cause mast cell degranulation without cross-linking Fc epsilon R1.

Answer 38

Typical examples include the complement components, C5a and C3a.

Question 39

How does phospholipase C gamma contribute to mast cell activation?

Answer 39

It catalyzes the breakdown of phosphatidylinositol bisphosphate to DAG and IP3.

Question 40

What is the effect of IP3 on the cell?

a. activates protein kinase C
b. increases the intracellular Ca++
c. upregulates Lyn activity
d. gets interconverted to PGD2

Answer 40

b. increases the intracellular Ca++

Question 41

Which enzymes act on the arachidonic acid after the release into the intracellular space?

Answer 41

Cyclooxygenase or lipoxygenase. Cyclooxygenase yields prostaglandin D2 (PGD2); lipooxygenage pathway yields leukotreins, specifically LTC4 and its degradation products LTD4 and LTE4

Question 42

What’s the adverse affect of H1 receptor antagonists (antihistamines)?

Answer 42

H1 receptor antagonists (commonly called antihistamines) can inhibit the vascular responses to intradermal allergen or anti-IgE antibody. Histamine also causes contraction of intestinal and bronchial smooth muscle. Thus, histamine may contribute to the increased peristalsis and bronchospasm associated with ingested and inhaled allergens, respectively.

Question 43

How does chymase affect the tissues after degranulation?

a. activation of collagenase and cleavage of fibrinogen
b. activation of serine proteases
c. coverts angiotensin I to angiotensin II
d. activation of carboxypeptidase

Answer 43

c. coverts angiotensin I to angiotensin II
chymase can convert angiotensin I to angiotensin II, which causes transient vasoconstriction, degrades epidermal basement membranes, and stimulate mucus secretion.

Question 44

Which immunoglobin mediates the type 2 hypersensitivity reactions?

a. IgE
b. IgG
c. IgA
d. IgM
e. IgD

Answer 44

b. IgG and d. IgM

Question 45

What are the receptors participating in the binding of effector cells type 2 hypersensitivity reactions?

Answer 45

Fc gamma R, C3R

Question 46

What inflammatory intermediates are synthesized from AA?

Answer 46

This metabolite is the precursor of eicosanoids - prostaglandins and leukotrienes

Question 47

What is “leukocyte frustration”? Does it even occur in a healthy individual?

Answer 47

“Leukocyte frustration” happens when the target of the effector cells are too large to be phagocytosed, so the contents of the cells are discharged through exocytosis. This reaction is normal when large pathogens such as schistosomes affect the individual.

Question 48

What are the effector cells in type 2 hypersensitivity reactions?

Answer 48

macrophages, neutrophils, eosinophils, NK cells

Question 49

What molecules protect the surface of nucleated cells from complement-mediated damage?

a. CD40 and CD44
b. CD4 and CD8
c. CD55 and CD59
d. CD54 and CD3

Answer 49

c. CD55 (decay accelerating factor) and CD59

Question 50

Which type of hypersensitivity cannot be transferred with serum antibody?

a. type 1
b. type 2
c. type 3
d. type 4
e. type 5

Answer 50

d. type 4
Unlike the other types of hypersensitivity (I, II, III, and V), type IV delayed-type reactivity cannot be transferred from a sensitized to a non-sensitized individual with serum antibody. T-lymphocytes are required. Type I hypersensitivity is caused by IgE antibodies. Type II hypersensitivity is caused by antibodies to cell surfaces. In rhesus incompatibility, it is maternal antibodies of the IgG class that cross the placenta and cause hemolytic disease of the fetus and newborn. Type III hypersensitivity is caused by antibody-containing immune complexes, which leads to undesirable complement activation and other immunopathological events. Type V is a stimulatory hypersensitivity caused by, for example, autoantibodies to hormone receptors that mimic the effect of the hormone. In neonatal thyrotoxicosis, it is transplacental transfer of the maternal stimulatory antibody that causes transient hyperthyroidism in the neonate.

Question 51

Anaphylaxis can be triggered by cross-linking of IgE receptors on:

a. monocytes
b. mast cells
c. B cells
d. eosinophils
e. T cells

Answer 51

b. mast cells
Cross-linking of IgE antibodies bound to the high affinity IgE receptor (FcϵRI) on mast cells by a bivalent antigen will trigger mediator release; trivalent antigens are more effective and tetravalent antigens even more so. Degranulation is also induced when the IgE is cross-linked with anti-IgE but univalent (Fab) anti-IgE is inactive. That the critical event is the cross-linking of the receptors themselves is clearly shown by the ability of antibodies reacting directly with the receptor to trigger the mast cell. CD23 (FcϵRII), the low affinity IgE receptor, is present on monocytes, B-cells, eosinophils, and T-cells. However, cross-linking does not result in anaphylaxis in any of these scenarios.

Question 52

Rhesus hemolytic disease of the fetus and newborn involves:

a. IgE
b. antibody to cell surfaces
c. soluble immune complexes
d. cytokine release from T-cells
e. stimulatory antibodies

Answer 52

b. antibody to cell surfaces
Rhesus incompatibility between mother and fetus leads to a type II hypersensitivity reaction caused by the passage across the placenta of IgG antibodies to the fetal RhD. Rhesus incompatibility is not a type I (IgE-mediated) hypersensitivity reaction. Rhesus incompatibility does not lead to a type III (immune complex-mediated) hypersensitivity reaction. Rhesus incompatibility does not lead to a type IV T-cell-mediated (delayed-type) hypersensitivity reaction. Rhesus incompatibility does not lead to a type V hypersensitivity reaction involving stimulatory antibodies.

Question 53

Where are mast cells predominantly located?

Answer 53

Mast cells are bone marrowderived cells that are widely distributed in the tissues. They are abundant near blood vessels and nerves and in subepithelial tissues, which explains why local immediate hypersensitivity reactions often occur at these sites.

Question 54

What can be used to dye the mast cells granules?

Answer 54

Mast cells have cytoplasmic membrane-bound granules that contain a variety of biologically active mediators. The granules also contain acidic proteoglycans that bind basic dyes such as toluidine blue.

Question 55

Which substance does NOT promote mast cell degranulation?

a. codeine
b. IL-8
c. mellitin
d. IL-1
e. adenosine

Answer 55

mast cell secretagogues include some chemokines (e.g., IL-8), drugs such as codeine and morphine, adenosine, mellitin (present in bee venom), and physical stimuli (heat, cold, and radiation)