Ig E, Ma, Eo

Sef lucr dr Adriana Muntean

Immunoglobulin E

• In 1967, IgE was identified as the unique

immunoglobulin that serves as the humoral “gatekeeper”
of type I hypersensitivity.
Ig E – distribution&metabolism
0,03-0,05 mg%

1. Circulating IgE 3,3 µg/kg of body weight T ½: 2,5 days

rate of synthesis – 2,3 µg/kg/day

2. Secretory IgE - respiratory and intestinal secretions

3. Bound to specific receptors (FcєRI, FcєRII) on blood basophils,
tissue mast cells and other immune cells – 1% T ½: 8-14 days

• IgE-forming plasma cells can be found in the lymphoid tissue of

the tonsils, adenoids, peritoneal area, respiratory and intestinal
mucosa.
• Most IgE production occurs in mucosal tissue sites.
Structure
IgE
A. How IgE forms

B. Mast cell and basophil

C. Control
 A. IgE formation
1. Antigen meets B cell

Ag
 A. IgE formation
1. Antigen meets B cell
2. B cell packages & presents Ag to helper T cell
 A. IgE formation
1. Antigen meets B cell
2. B cell packages &
presents Ag to Th cell
1. B cell proliferates
 A. IgE formation
1. Antigen meets B cell
2. B cell packages & presents Ag to helper T cell
3. B cell proliferates
4. A switch to IgE
 A. IgE production
1. Antigen meets B cell
2. B cell packages & CD40L
presents Ag to Th cell
1. B cell proliferates
2. A switch to IgE IL4

“class switch recombination”

 A. IgE production
1. Antigen meets B cell Memory cell
2. B cell packages &
presents Ag to Th cell
1. B cell proliferates
2. Plasma cells & memory
cells
 B. Basophil & Mast cell
IgE binds to the mast cell

HOW?
 B. Mast Cell
IgE binds to the mast cell

HOW?

FcRI
 B. Mast Cell

FcRI
• High affinity
• 200 000/cell
• 10% occupancy works fully!
 B. Mast Cell
De

Ag
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ul
a tio
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 B. Mast Cell
De

Ag
gr
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 B. Mast Cell
De

Ag
gr
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MASTOCITE
 MEDIATORs Ma
• heparin proteoglycan (an anticoagulant)
• serotonin
• dopamine
• tryptase (mast cells located in mucosal areas have a higher level of tryptase
than mast cells in connective tissue)
• chymase
• histamine (a substance that causes vasodilation and increased permeability
of capillaries)
• neutral proteases
• eosinophil chemotactic factor of anaphylaxis (ECF-A)
• phospholipases activation, which results in the secretion of
¤ prostoglandins and
¤ leukotrienes (also called slow reacting substance of anaphylaxis, SRS-A)
• Pro-inflammatory cytokines:
¤ IL-4, IL-5, IL-6, IL-13, IL-18, IFN-γ, TNF-α
• Chemokines:
¤ MCP-1, IL-8, RANTES, eotaxin, leukotriene
• Proteases:
¤ Tryptase, chymase, angiotensin converting enzyme (ACE),
carboxypeptidase, cathepsin G, cysteinyl cathepsins
• Hematopoeitic factors:
¤ IL-3, GM-CSF
• Growth factors:
¤ bFGF, VEGF, TGF-beta, PDGF
• Chondroitin sulfate proteoglycan
 B. Mast Cell
Degranulation
• Serotonin
• Pg, leukotrienes Histamine
• Proteases
• Chemokines (H1, H2, H3, H4)
• Cytokines
 B. Mast Cell
Target organs
ANAPHYLAXIS
• Lungs
Cardiovascular
• Heart
collapse
• Vasculature
Urticaria
• Cutaneous
Bronchospasm
 B. The Basophil

• < 1% of white cells

• No/↓ tryptase
• Lots of histamine
• Rich in FcRI

Late phase?
 C. Control
Massively complex

• Th1 versus Th2

• Genetic factors
• The dendritic cell
• FcRII
• Innate Immunity!
 Total IgE level
Age Level (IU/ml)
<1 year <15
1-5 years <60
6-9 years <90
10-15 years <200
Adult <100

Serum total IgE concentrations in normal children and adults are

highly variable, ranging from approximately 2 to over 100 IU/mL
(1 IU = 2.4 ng of IgE)

IgE may be synthetized early in the uterine life and it can be

detected in cord blood.
Ce afectiuni cu IgE crescut gasiti?
What diseases with increased IgE do You find?
A high level of
total serum
IgE is NOT a
marker of
allergy!
 Clinical allergy versus sensitisation

Stiefel G , Roberts G Arch Dis Child Educ Pract Ed 2012;97:29-

36

Copyright © BMJ Publishing Group Ltd & Royal College of Paediatrics and Child Health. All rights reserved.
 Adevarat(true) sau (or) Fals?
1. IgE totale crescute (increased)= Alergie (allergy)
2. IgE traverseaza placenta (cross placenta)
3. IgE specifice<0,35 ku/L = sensibilizare
(sensitization)
4. Il-4 = factor ce augumenteaza sinteza IgE
(increase IgE sintesis)
5. IgE specifice pot fi detectate in sangele din
cordonul ombilical (can be detected in cord
blood)