Lecture 17: IgE Flashcards
What kind of hypersensitivity reaction is allergy?
Type 1
Define allergy
disease following immune response to otherwise innocuous antigen
Define atopy
The ability to transfer reactivity to allergens by means of serum (aka the ability to make IgE)
True or false: allergic reactions have double in the past 10-15 years
True
What are some clinical manifestations of allergy?
smooth muscle spasm
increased vascular permeability
activation of inflammatory and coagulation cascades
What is a major post translational modification on IgE molecules?
heavy glycosylation
How abundant is IgE in serum?
usually VERY LOW concentrations (it is a cell bound antibody found mainly at host-environmental interfaces)
Where are the binding sites for FcERs? (what cells have them)
mast cells and basophils (and on APCs at much lower levels)
What do basophils and mast cells have in common?
1) cytoplasmic stores of histamine, TNFa, and leukotrienes
2) high affinity IgE FcE receptors
__________ are tissue bound while ________ are mostly in the blood
mast cells; basophils
What are the two toxic mediators in mast cells?
1) histamine
2) heparin
What is the lipid meditator in mast cells?
leukotrienes
What distinguishing feature divides the two major subtypes of mast cells?
what enzymes are expressed
MCt = tryptase MCtc = tryptase and chymase
(but since both have tryptase, tryptase staining is the primary way to identify mast cells)
____ are the primary mast cells of the mucosa while _____ are in the connective tissue like skin
MCt; MCtc
What is one characteristic that many allergens have in common?
contain Chitin
What dictates our allergic responses?
our genes (50% of children from 2 atopic parents will be atopic)
Which MHC presents allergens?
2 (D class perhaps promotes IgE production over IgG by influencing the type of TLR activated)
What gene(s) are responsible for allergic reactions?
A multiplicity of them! act in concert
True or false: there is a direct relationship between serum IgE levels, allergic reactions and the atopic state
True
Almost anything can be an allergen but what heightens the probability that our immune system will mount a response?
enzymatic activity
What is one big reason for why timing is important in the allergic response?
decreased early exposure to infections in genetically predisposed individuals is associated with insufficient Treg control of IgE
What is the common route of allergens?
mucosal
How does the body know if it is taking up allergen or actual pathogen? (in other words, what pushes the processing towards the IgE route vs the IgG?)
“allergic” TLRs that induce DC to produce IL-4 instead of IL-12 (Th2 instead of normal Th1)
also, presentation of peptide as well as the nature of it shift it towards the dominant IgE
Allergic responses are dependent on what kind of responses?
Th2
What leads to the Th2 response?
presence of IL-4 and lack of IL-12
What 2 cytokines dominate the profile during IgE responses?
IL-4 and IL-13
What is the ONLY receprot that can be occupied without antigen?
FCeR
Fc receptor for IgE wants to bind empty IgE - then the cell is armed and ready
What is required for degranulation of mast cells and basophils?
crosslinking of IgE receptors
What promotes IgE class switching?
upregulation of CD23 on mast cells and basophils that increase their production of IL-4 and 13
What happens within the first 15 minutes (immediate reaction) of an allergic reaction?
prostaglandin and leukotriene release; direct complement activation by tryptase (BUT YOU NEED PRIOR EXPOSURE)
characterized by mast cells and basophils
What is the late phase (slow-acting - takes hours) of an allergic reaction characterized by?
eosinophils
The late phase is completely dependent on T cell activation as well as which cytokines?
IL-3, 4, 5, 13, TNFa, GM-CSF, IL-10
What cytokine stimulates release of eosinophils from the bone marrow?
IL-5
eotaxin chemokine also helps
How does IL-5 help in the allergic response?
increases FceR display (augments IgE)
Which inflammatory enhancer is produced by eosinophils?
major basic protein
Clinical manifestations of the allergic response are dependent on what?
site of reaction
What is anaphylaxis and when does it come on?
immediately; bronchiolar constriction and increased vascular permeability
blood pressure plummets, heart rate rises
What is allergic rhinitis?
occurs when allergen binds to cells in the nasal submucosa and incites chronic allergic reaction
What is uticaria?
hives (occur when IgE armed mast cells are activated in the skin)
What is the hygiene hypothesis?
decreased childhood infection is increasing allergies
worm infected children that are treated develop allergies
What is the support for hygiene hypothesis?
evidence that early exposure to childhood illness sets normal Th1 and Th2 responses to subsequent environmental antigen exposure
What is the most important component in diagnosing allergies?
taking a careful history
What is the RAST test?
Radio Allergo Sorbent Test
add patient serum to cellulose disc with allergen, if IgE is present in the serum, it will bind. After washing, add radio labeled anti-IgE then count with a gamma counter
In addition to RAST, what other test can you do?
skin test
True or false: diagnostic tests are only used as adjunct to clinical symptoms
True
What is a common treatment for allergies?
anti-IgE
What is another, clever treatment to allergies?
allergen immunotherapy (reroute IgE response by administering allergen antigens that promote Th1 response to culminate in IgG production (blocking antibodies))
