L22: IgE & Allergy

Question 1

Type 1 hypersensitivity reaction

Answer 1

another term for allergic response

Question 2

This portion of the reaction is completely dependent on previous exposure and sensitization

Answer 2

Immediate reaction of Type 1 hypersensitivity

Question 3

Denotes the ability to transfer reactivity to allergens by means of serum (transfer agent is IgE)

Answer 3

Atopy

Question 4

A disease following a response by the immune system to an otherwise innocuous antigen.

Answer 4

Allergy

Question 5

Examples of allergic reactions

Answer 5

Anaphylactic shock
Allergic rhinitis
Bronchial asthma

Question 6

Mast cells and basophils constitutively express

Answer 6

high affinity IgE Fc receptors

Question 7

Basophiles are

Answer 7

circulating leukocytes

Question 8

2 major subtypes of mast cells

Answer 8

MCT (tryptase) - found in mucosa

MCTC (tryptase and chymase) - connective tissue

Question 9

Mast cells contain large amounts of

Answer 9

histamine
heparin
preteases
Leukotriene B4
Inflammatory cytokines (litany)
TNF-alpha
Chemokines
GM-CSF

Question 10

Name some allergen types

Answer 10

Aero-allergens
Food allergens
Insect venoms
Chitin
Drugs (eg. antibiotics)

Question 11

How does the APC (a DC) preferentially activate IgE production programs?

Answer 11

Immunodominant peptides in allergens are preferentially selected by MHC II class D loci, which act IN CONCERT with other non-MHC genes to influence the type of TLR activated, T-helper cell, and cytokine milieu!

Question 12

Talk to me about the unique context for INITIATING an allergic reaction

Answer 12

Genetic predisposition for atopy. Multiplicity of genes act in concert to produce allergic reaction (bottom line). There’s a direct relationship between serum IgE, allergic reaction, and atopic state!

Question 13

Why does timing of exposure matter?

Answer 13

An unusually high level of exposure
very early in life coupled with a relative LACK of exposure to infectious disease antigens that incite vigorous Th1 and Th2 responses will manifest by IgE production and allergy to some, but not all antigens, in lieu of an expected Th1 or IgG response.

Question 14

Upon uptake of allergen, DC’s secrete what cytokine?

Answer 14

IL4

Question 15

allergic responses are dependent on what Th reaction?

Answer 15

Th2

Question 16

The accelerated production of Th-2 cytokines, especially ____ and _____ dominate the cytokine profile.

Answer 16

IL4 and IL13

Question 17

What promotes IgE class switching?

Answer 17

Promotion of IgE class switching occurs by up regulation of CD-23 (FcεRII
receptor) on mast cells and basophils that increase their production of IL-4
and IL-13. This is strongly influenced by gene influenced polymorphisms.

Question 18

What activates activate ε germ-line transcription in B-cells and results in IgE synthesis?

Answer 18

IL4 from Th2, Basophils, and mast cells

Question 19

What is so special about the FcεR on basophils and mast cells? Hint: think “arming” the FcεR…

Answer 19

The FcεR is the ONLY FcR that can be occupied by antibody not previously complexed with antigen.

Question 20

What causes cross linking of FcεR on armed basophils or mast cells?

Answer 20

Subsequent exposure to the same allergen then cross-links the IgE previously bound to FcεR receptors.

Question 21

What triggers degranulation of basophils and mast cells?

Answer 21

Signal transduction activates calcium influx into armed mast cells and basophils which then degranulate, releasing potent vasoactive, inflammatory and
fibrogenic mediators.

Question 22

where did I leave off?

Answer 22

handout on immediate reaction