IgE Immunology Flashcards
What is type I hypersensitivity disease and what is it mediated by?
Allergic responses, mediated by IgE
What is type II hypersensitivity disease and what is it mediated by?
Ab directed against tissue antigens, mediated by IgG
What is type III hypersensitivity disease and what is it mediated by?
Immune complex mediated disease, mediated by Ag + IgG
What is type IV hypersensitivity disease and what is it mediated by?
Delayed hypersensitivity disease, mediated by T cells
What cells are most responsible for allergic symptoms?
Eosinophils, mast cells, basophils
define allergy
a disease induced by a reaction to a usually innocuousAg
Define atopy
genetic predisposition to develop IgE antibodies upon exposure to environmental allergens
What cells does IgE interact with?
Mast cells and basophils have high affinity Fc-epsilon-R that can bind the Fc region of IgE
What do mast cells and basophils have in their cytoplasm?
histamine, TNF-alpha, leukotrienes
What are the toxic mediators of mast cells?
histamine and heparin
What are the lipid mediators of mast cells?
leukotrienes - LTC4, LTD4, LTE4
What enzymes do mast cells contain?
Tryptase, chymase, cathepsin G, carboxypeptidase
What cytokines do mast cells release?
IL-4, IL-13, IL-3, IL-5, GM-CSF, TNF-alpha
What chemokines do mast cells release?
MIP-1a
what are the two types of mast cells?
MC(t): tryptase
Skin MC(tc): tryptase and chymase
What is a characteristic of many allergens?
they contain chitin – a polysaccharide not found in humans
What can induce an allergic response in an atopic individual?
almost any protein
if two parents are atopic, what is the chance their children ill be atopic?
50%
What are basophils?
circulating leukocytes
Where are MC(t) cells found?
prominent mast cell type within the mucosa of the respiratory and gastrointestinal tracts and increase with mucosal inflammation
Where are MC(tc) cells found?
localized within connective tissues, such as the dermis, submucosa of the gastrointestinal tract, heart, conjunctivae, and perivascular tissues
What MHC class are the immunodominant peptides of allergens presented by?
Class II D MHC of dendritic cells
What do the D and non-MHC genes do?
promote IgE production over IgG responses by influencing the type of TLR activated, type of T-helper cell and cytokine milieu present during allergen presentation by APC
what is the relationship between atopy, serum levels of IgE, and allergic reactions?
direct relationship
What are some examples of genes that can influence the allergic response?
varying expression of IFN-γ via the T-Bet gene, FcεR avidity via a maternal gene, IgE synthesis and bronchial reactivity, IL-13 synthesis
How is MHC involved in the allergic response?
Different MHC-II will present different peptides that differ in their antigenic potency
Almost anything can be an allergen. However, what is the trend towards?
proteins with enzymatic activity
How is timing important in developing allergies?
decreased early exposure to infections in the genetically predisposed individual is associated with insufficient T regulator control of IgE
what kind of route predominates in an allergic response?
mucosal
Discuss the chain of events that leads to an allergic response
Allergen crosses mucosal epithelia and is taken up by dendritic cell
dendritic cell presents to a B cell in the lymph nodes and a Th2 cell prompts switching of B cell to IgE production
plasma cell releases Ab specific for the Ag at the site of entry
IgE binds to Fc-epsilon-RI on mast cell, and upon Ag binding, leads to the release of mast cell granules which cause allergic symptoms
What is the only FcR that can be occupied by Ab without antigen?
Fc-epsilon-R
Fc-e-RI has a relative binding strength of 20,000x
What is the temporal sequence of mast cell release?
histamines and prostaglandins are released within seconds of IgE cross linking
leukotrienes are released 10-15 minutes later
What is the early phase of an allergic reaction?
within 15 minutes prostaglandin and leukotriene release and direct complement activation
Can the early phase occur if there has not been a previous exposure?
No!
What is the late phase of an allergic reaction dependent upon?
completely dependent on Th2
What cytokines are released in the late phase of an allergic reaction?
IL3, 4, 5, 10, 13
What is the late phase of an allergic reaction characterized by?
Eosinophils
What is the clinical manifestation of an allergic response dependent upon?
The site of reaction
What is the main organ and route of entry for anaphylaxis?
systemic
Stings, Ingestion, Inhalation(rare)
What are the typical allergens and main symptoms of anaphylaxis?
insect venom, drugs, food
shock, hypotension, wheezing, urticaria, angioedema
What is the main organ and route of entry for Eczema (atopic dermatitis), Urticaria, and Angioedema?
Skin and other various organs
contact, ingestion, inhalation (rare)
What are the typical allergens and main symptoms of Eczema (atopic dermatitis), Urticaria, and Angioedema?
uncertain, various foods, drugs
Pruritic, vesicular, and swollen lesions
What is the main organ and route of entry for Allergic Rhinitis and Conjunctivitis?
Nose and eyes
contact with mucous membrane
What are the typical allergens and main symptoms of Allergic Rhinitis and Conjunctivitis?
Pollens, dust mites, animal dander, molds
Runny nose, redness and itching of eyes
What is the main organ and route of entry for asthma?
Lungs
inhalation
What are the typical allergens and main symptoms of asthma?
Pollens, dust mites, animal dander, molds
Wheezing, dyspnea, tachypnea
What is the main organ and route of entry for Allergic gastroenteropathy?
Gastro-intestinal tract
ingestion
What are the typical allergens and main symptoms of alleric gastroenteropathy?
various foods
Pain, bloating, vomiting, diarrhea
What is the result of a high dose intravenous allergen?
general histamine release by connective tissue mast cells, which acts on blood vessels to increase permeability, leading to systemic anaphylactic shock
what is the result of a low dose subcutaneous allergen?
local histamine release by connective tissue mast cells causing wheal and flare reactions
What is the result of low dose inhaled allergen?
allergic rhinitis (upper airway) caused by increased mucous production and nasal irritation
asthma (lower airway) due to contraction of bronchial smooth muscle and increased mucous production
What is the result of ingestion of an allergen?
contraction of intestinal smooth muscle leads to vomiting
outflow of fluid into the gut causes diarrhea
antigen diffuses into the blood stream causing urticaria, anaphylaxis, or atopic eczema
How do you test for allergen in people?
in-vivo - skin testing
in vitro - RAST
What is the positive control in a skin test?
histamine
How do you do the RAST assay?
add pt serum to a cellulose disc with covalently bound allergen
IgE present in serum will bind to allergen
wash, add radio-labeled anti-IgE, measure
How would you mitigate the effects of the allergic mediators?
antihistamines, beta blockers, lipoxygenase inhibitors
How would you treat chronic inflammatory reactions?
general anti-inflammatory effects via corticosteroids
how would you treat the Th2 response of an allergic reaction?
induction of Tregs, desensitization by injection of specific Ag
how would you prevent IgE binding to the mast cell?
Anti-IgE Ab would bind to Fc region and prevent binding to Fc receptor
