IgE Allergy

Question 1

What is Atopy?

Answer 1

genetic predisposition to develop IgE antibodies upon exposure to environmental allergens

Question 2

Where are IgE normally levels very low? Where are the basophils which have bind IgE with their FcE receptors normally found?

Answer 2

normally very low serum concentrations
-cell bound antibody mostly found at host-environmental interfaces

-basophils mostly in the blood

Question 3

What do mast cells and basophils both express and contain?

Answer 3

• high affinity FcE receptor

- contain histamine, TNF alpha, and leukotrienes in cytoplasm

Question 4

Where are mast cells mostly found?

Answer 4

tissue bound, compartmentalized as mucosal or connective tissue
-contain potent vasoactive compounds and cytokines

Question 5

What are the two types of mast cells where are they found?

Answer 5

MC-Tryptase= Mucosal

MC- Tryptase and Chymase= connective tissue

Question 6

What is a characteristic many allergens contain? What does this induce expression of?

Answer 6

Chitin-a polysaccharide not found in mammals

Induces expression of:
Chitinase
-a possible inducer of allergenic antigen generation and release of vasoactive mediators

Question 7

Are allergic responses dictated by genes?

Answer 7

yes
-Different MHC-2 will present different peptides that differ their antigenic potency

Examples:
1. varying gene expression of INF gamma via the T-Bet gene

2. FcER avidity via maternal genes
3. IgE synthesis and bronchial reactivity
4. Il 13 synthesis

Question 8

What types of antigens tend to cause allergic reactions?

Answer 8

-proteins with enzymatic activity or proteins that induce enzymatic activity

Question 9

If there is decreased early exposure to infections in the genetically predisposed individual is this good for T-reg control of IgE?

Answer 9

NO

-associated with insufficient T reg control of IgE

Question 10

How are most antigens exposed that cause allergy?

Answer 10

mucosal exposures predominate

Question 11

Does IgE bind FcE receptors on mast cells even when there is no antigen present? What happens when there is antigen present?

Answer 11

Yes! bound to resting mast cells

When antigen present, crosslinks bound IgE antibody causing the release of granules

Question 12

What is the immediate reaction that happens within 15 minutes of allergen response?
Can this happen if there is no previous exposure?

Answer 12

-multiple vasoactive mediators released from mast cells and basophils
prostaglandins and leukotriene release
-direct complement activation by tryptase (released from mast cell)

***Cannot happen if there is no previous exposure

Question 13

What is the late phase defined as? What is this phase dependent on?

Answer 13

• within hours of allergen contact
• completely dependent on T-cell activation
• and presence of IL3,4,5,13, TNF alpha, GM-CSF, and IL10

Question 14

What comes in the late phase of the response?

Answer 14

Eosinophils

Question 15

What regulate the release and growth of eosinophils?

Answer 15

13, 5, eotaxin

Question 16

What does IL5 do?

Answer 16

increases FcR display and thereby augments the IgE reaction

Question 17

What do eosinophils produce?

Answer 17

unique inflammatory enhancers

1. major basic protein *
2. leukotrienes
3. cationic proteins

Question 18

What type of reaction is an allergic response?

Answer 18

Type 1 hypersensitivity reaction

Question 19

What are normal IgE responses to?

Answer 19

relatively biodegradable resistant antigens

Question 20

What do mast cells contain? WHat is their function?

Answer 20

Histamine, Heparin, Proteases, Newly synthesized leukotrien B4, and inflammatory cell cytokines: IL 3,4,5,6,8,10, 13 and TNF alpha
and chemokines and GM-CSF
–>allergic inflammation

Also do:

1. antigen presentation
2. direct effect on B-cells to produce IgE

Question 21

What are some types of allergens?

Answer 21

Aero-allergens (pollen)
Food Allergens
Insect venoms 
Chitin 
Many drugs( especially antibiotics)

Question 22

What are immunodominant peptides of these allergens usually preferentially presented in?

Answer 22

(class 2) D MHC loci by dendritic cells

Question 23

What promotes IgE responses over IgG?

Answer 23

D genes and other non MHC genes by influencing the type of TLR activated, the type of Thelper cell, and cytokine milieu present during allergy presentation by APC

Question 24

What happens when there is an unusually high level of exposure very early in life coupled with a lack of exposure to infectious disease antigens that incite vigorous Th1 and Th2 responses

and

Very small amounts to mucosal surfaces

and

Genetically predisposed
?

Answer 24

IgE production and allergy to some but not all antigens

Question 25

What is the sequence to get to production of IgE?

Answer 25

1. contact with the allergen (usually mucosal, resp or gi)
2. DC takes up antigen via allergic TLR
3. DC produce IL-4
4. Presentation of the allergen as an immunodominant peptide in class 2 MHC groove
5. Th2 activation
6. Th2 provides critical IL-4 signal to allergen specific B-cell
7. Th2 cytokines=IL4 and IL 13 dominate
8. Promotion of IgE class switching
   occurs by:
   -up regulation of CD-23 (FcER2) on mast cells and basophils–>increase in their production of IL 4 and IL 13
   -this is strongly influenced by gene polymorphisms
9. IL 4 from Th2 and basophils and mast cells activate E germ line transcription in B-cells and results in IgE synthesis

Question 26

What is the most important factor in arriving at the correct diagnosis of allergic response?

Answer 26

CLINICAL HISTORY

Question 27

What is rast? What is an in vivo test you can do instead that is more sensitive?

Answer 27

RAST

• radio allergo sorbent test
• in vitro assay-allergen in solid phase, add patient serum, IgE in serum binds allergen, radioactive anti-IgE

In Vivo :
skin test

Question 28

What is a therapy for allergens?

Answer 28

anti-IgE therapy
-decrease eosinophilic inflammation and IgE-bearing cells

Allergen immunotherapy
-rerouting of IgE response by admin allergen antigens that promote either Th1 response and macrophage destruction or Th2 response that accumulate IgG production

-sublingual or oral