IgE Allergy Flashcards
What is Atopy?
genetic predisposition to develop IgE antibodies upon exposure to environmental allergens
Where are IgE normally levels very low? Where are the basophils which have bind IgE with their FcE receptors normally found?
normally very low serum concentrations
-cell bound antibody mostly found at host-environmental interfaces
-basophils mostly in the blood
What do mast cells and basophils both express and contain?
- high affinity FcE receptor
- contain histamine, TNF alpha, and leukotrienes in cytoplasm
Where are mast cells mostly found?
tissue bound, compartmentalized as mucosal or connective tissue
-contain potent vasoactive compounds and cytokines
What are the two types of mast cells where are they found?
MC-Tryptase= Mucosal
MC- Tryptase and Chymase= connective tissue
What is a characteristic many allergens contain? What does this induce expression of?
Chitin-a polysaccharide not found in mammals
Induces expression of:
Chitinase
-a possible inducer of allergenic antigen generation and release of vasoactive mediators
Are allergic responses dictated by genes?
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
- FcER avidity via maternal genes
- IgE synthesis and bronchial reactivity
- Il 13 synthesis
What types of antigens tend to cause allergic reactions?
-proteins with enzymatic activity or proteins that induce enzymatic activity
If there is decreased early exposure to infections in the genetically predisposed individual is this good for T-reg control of IgE?
NO
-associated with insufficient T reg control of IgE
How are most antigens exposed that cause allergy?
mucosal exposures predominate
Does IgE bind FcE receptors on mast cells even when there is no antigen present? What happens when there is antigen present?
Yes! bound to resting mast cells
When antigen present, crosslinks bound IgE antibody causing the release of granules
What is the immediate reaction that happens within 15 minutes of allergen response?
Can this happen if there is no previous exposure?
-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
What is the late phase defined as? What is this phase dependent on?
- within hours of allergen contact
- completely dependent on T-cell activation
- and presence of IL3,4,5,13, TNF alpha, GM-CSF, and IL10
What comes in the late phase of the response?
Eosinophils
What regulate the release and growth of eosinophils?
13, 5, eotaxin
What does IL5 do?
increases FcR display and thereby augments the IgE reaction
What do eosinophils produce?
unique inflammatory enhancers
- major basic protein *
- leukotrienes
- cationic proteins
What type of reaction is an allergic response?
Type 1 hypersensitivity reaction
What are normal IgE responses to?
relatively biodegradable resistant antigens
What do mast cells contain? WHat is their function?
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:
- antigen presentation
- direct effect on B-cells to produce IgE
What are some types of allergens?
Aero-allergens (pollen) Food Allergens Insect venoms Chitin Many drugs( especially antibiotics)
What are immunodominant peptides of these allergens usually preferentially presented in?
(class 2) D MHC loci by dendritic cells
What promotes IgE responses over IgG?
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
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
?
IgE production and allergy to some but not all antigens
