IgE Immunology Flashcards by Steven Marincel

What is type I hypersensitivity disease and what is it mediated by?

Allergic responses, mediated by IgE

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What is type II hypersensitivity disease and what is it mediated by?

Ab directed against tissue antigens, mediated by IgG

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What is type III hypersensitivity disease and what is it mediated by?

Immune complex mediated disease, mediated by Ag + IgG

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What is type IV hypersensitivity disease and what is it mediated by?

Delayed hypersensitivity disease, mediated by T cells

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What cells are most responsible for allergic symptoms?

Eosinophils, mast cells, basophils

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define allergy

a disease induced by a reaction to a usually innocuousAg

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Define atopy

genetic predisposition to develop IgE antibodies upon exposure to environmental allergens

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What cells does IgE interact with?

Mast cells and basophils have high affinity Fc-epsilon-R that can bind the Fc region of IgE

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What do mast cells and basophils have in their cytoplasm?

histamine, TNF-alpha, leukotrienes

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What are the toxic mediators of mast cells?

histamine and heparin

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What are the lipid mediators of mast cells?

leukotrienes - LTC4, LTD4, LTE4

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What enzymes do mast cells contain?

Tryptase, chymase, cathepsin G, carboxypeptidase

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What cytokines do mast cells release?

IL-4, IL-13, IL-3, IL-5, GM-CSF, TNF-alpha

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What chemokines do mast cells release?

MIP-1a

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what are the two types of mast cells?

MC(t): tryptase

Skin MC(tc): tryptase and chymase

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What is a characteristic of many allergens?

they contain chitin – a polysaccharide not found in humans

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What can induce an allergic response in an atopic individual?

almost any protein

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if two parents are atopic, what is the chance their children ill be atopic?

50%

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What are basophils?

circulating leukocytes

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Where are MC(t) cells found?

prominent mast cell type within the mucosa of the respiratory and gastrointestinal tracts and increase with mucosal inflammation

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Where are MC(tc) cells found?

localized within connective tissues, such as the dermis, submucosa of the gastrointestinal tract, heart, conjunctivae, and perivascular tissues

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What MHC class are the immunodominant peptides of allergens presented by?

Class II D MHC of dendritic cells

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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

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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