Lecture 17: IgE

Question 1

What kind of hypersensitivity reaction is allergy?

Answer 1

Type 1

Question 2

Define allergy

Answer 2

disease following immune response to otherwise innocuous antigen

Question 3

Define atopy

Answer 3

The ability to transfer reactivity to allergens by means of serum (aka the ability to make IgE)

Question 4

True or false: allergic reactions have double in the past 10-15 years

Answer 4

True

Question 5

What are some clinical manifestations of allergy?

Answer 5

smooth muscle spasm
increased vascular permeability
activation of inflammatory and coagulation cascades

Question 6

What is a major post translational modification on IgE molecules?

Answer 6

heavy glycosylation

Question 7

How abundant is IgE in serum?

Answer 7

usually VERY LOW concentrations (it is a cell bound antibody found mainly at host-environmental interfaces)

Question 8

Where are the binding sites for FcERs? (what cells have them)

Answer 8

mast cells and basophils (and on APCs at much lower levels)

Question 9

What do basophils and mast cells have in common?

Answer 9

1) cytoplasmic stores of histamine, TNFa, and leukotrienes

2) high affinity IgE FcE receptors

Question 10

__________ are tissue bound while ________ are mostly in the blood

Answer 10

mast cells; basophils

Question 11

What are the two toxic mediators in mast cells?

Answer 11

1) histamine

2) heparin

Question 12

What is the lipid meditator in mast cells?

Answer 12

leukotrienes

Question 13

What distinguishing feature divides the two major subtypes of mast cells?

Answer 13

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)

Question 14

____ are the primary mast cells of the mucosa while _____ are in the connective tissue like skin

Answer 14

MCt; MCtc

Question 15

What is one characteristic that many allergens have in common?

Answer 15

contain Chitin

Question 16

What dictates our allergic responses?

Answer 16

our genes (50% of children from 2 atopic parents will be atopic)

Question 17

Which MHC presents allergens?

Answer 17

2 (D class perhaps promotes IgE production over IgG by influencing the type of TLR activated)

Question 18

What gene(s) are responsible for allergic reactions?

Answer 18

A multiplicity of them! act in concert

Question 19

True or false: there is a direct relationship between serum IgE levels, allergic reactions and the atopic state

Answer 19

True

Question 20

Almost anything can be an allergen but what heightens the probability that our immune system will mount a response?

Answer 20

enzymatic activity

Question 21

What is one big reason for why timing is important in the allergic response?

Answer 21

decreased early exposure to infections in genetically predisposed individuals is associated with insufficient Treg control of IgE

Question 22

What is the common route of allergens?

Answer 22

mucosal

Question 23

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?)

Answer 23

“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

Question 24

Allergic responses are dependent on what kind of responses?

Answer 24

Th2

Question 25

What leads to the Th2 response?

Answer 25

presence of IL-4 and lack of IL-12

Question 26

What 2 cytokines dominate the profile during IgE responses?

Answer 26

IL-4 and IL-13

Question 27

What is the ONLY receprot that can be occupied without antigen?

Answer 27

FCeR | Fc receptor for IgE wants to bind empty IgE - then the cell is armed and ready

Question 28

What is required for degranulation of mast cells and basophils?

Answer 28

crosslinking of IgE receptors

Question 29

What promotes IgE class switching?

Answer 29

upregulation of CD23 on mast cells and basophils that increase their production of IL-4 and 13

Question 30

What happens within the first 15 minutes (immediate reaction) of an allergic reaction?

Answer 30

prostaglandin and leukotriene release; direct complement activation by tryptase (BUT YOU NEED PRIOR EXPOSURE) characterized by mast cells and basophils

Question 31

What is the late phase (slow-acting - takes hours) of an allergic reaction characterized by?

Answer 31

eosinophils

Question 32

The late phase is completely dependent on T cell activation as well as which cytokines?

Answer 32

IL-3, 4, 5, 13, TNFa, GM-CSF, IL-10

Question 33

What cytokine stimulates release of eosinophils from the bone marrow?

Answer 33

IL-5 | eotaxin chemokine also helps

Question 34

How does IL-5 help in the allergic response?

Answer 34

increases FceR display (augments IgE)

Question 35

Which inflammatory enhancer is produced by eosinophils?

Answer 35

major basic protein

Question 36

Clinical manifestations of the allergic response are dependent on what?

Answer 36

site of reaction

Question 37

What is anaphylaxis and when does it come on?

Answer 37

immediately; bronchiolar constriction and increased vascular permeability blood pressure plummets, heart rate rises

Question 38

What is allergic rhinitis?

Answer 38

occurs when allergen binds to cells in the nasal submucosa and incites chronic allergic reaction

Question 39

What is uticaria?

Answer 39

hives (occur when IgE armed mast cells are activated in the skin)

Question 40

What is the hygiene hypothesis?

Answer 40

decreased childhood infection is increasing allergies | worm infected children that are treated develop allergies

Question 41

What is the support for hygiene hypothesis?

Answer 41

evidence that early exposure to childhood illness sets normal Th1 and Th2 responses to subsequent environmental antigen exposure

Question 42

What is the most important component in diagnosing allergies?

Answer 42

taking a careful history

Question 43

What is the RAST test?

Answer 43

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

Question 44

In addition to RAST, what other test can you do?

Answer 44

skin test

Question 45

True or false: diagnostic tests are only used as adjunct to clinical symptoms

Answer 45

True

Question 46

What is a common treatment for allergies?

Answer 46

anti-IgE

Question 47

What is another, clever treatment to allergies?

Answer 47

allergen immunotherapy (reroute IgE response by administering allergen antigens that promote Th1 response to culminate in IgG production (blocking antibodies))