MW L2 Asthma & allergy

Question 1

Allergy is what type of hypersentivity

Answer 1

Type 1

IgE mediated

Question 2

What is allergy?

Answer 2

A change in reactivity

Question 3

Not all asthmatics are allergic but what is similar?

Answer 3

Inflammation - mediators and cell content

Question 4

Extrinsic is associated with atopic/non-atopic?
Young/middle onset?
More severe airflow limitation?

Answer 4

atopic
young
less severe

Question 5

Allergy is driven by …. cells and their products ……..

Answer 5

Th2 cells

Th2 cytokines

Question 6

Allergic people are often born…

Answer 6

during grass pollen season - because the immune system when born is skewed to certain cytokines and this is more likely to get allergy when reexposed

Question 7

Strongest link for developing allergy?

Answer 7

Genetic - parents with allergy

Question 8

Th1 cells produce….

Answer 8

IFN gamma
OR
IL12

Question 9

Th2 cells produce….

Answer 9

IL2 and IL13 (similar/ overlap receptors)
OR
IL5
OR
IL9

Question 10

What suppressed Th2 production?

Answer 10

Th1 cytokines (and vice versa). 
Allergy is associated with imbalance of this

Question 11

What cells become Th1 or Th2 cells?

Answer 11

Th0 - non-polarised cells

Question 12

How does sensitisation to allergen occur?

Answer 12

Presenting cells bind to a foreign agent, send out signals attracting T cells. T cells recognise and you get a highly specific clonal selection. Expansion of population. Th0 cells become Th1 or Th2

Question 13

Factors factoring the Th1 phenotype: (4)

Answer 13

Older siblings
Early exposure to daycare
TB, measles, hep A
Rural

Question 14

Factors favouring Th2 phenotype: (5)

Answer 14

Antibiotics
Western lifestyle
Urban
Diet
Dust mites and cockroaches

Question 15

What makes IgE antibody?

Answer 15

Activated B cells

Question 16

How does B cell become activated?

Answer 16

Th2 produces IL4 and IL13 which activate B cell.

Question 17

What happens to IgE?

Answer 17

Binds to mast cells and waits like a detonator.

A second antigen exposure sets off reaction later.

Question 18

Is IgE rare/common

Answer 18

Rare

Question 19

What does E in IgE stand for?

Answer 19

‘Erythematous’

Question 20

What region of IgE binds to what cells?

Answer 20

Fc region binds to FceR1

on mast cells and basophils

Question 21

What causes degranulation of mast cells?

Answer 21

Cross linking of FceR1 - bound IgE on mast cell surface.

Binding arms it and cross linking produces degranulation.

Question 22

Time course: initial sensitisation may take…

Answer 22

years

Question 23

What does mast cells release when degranulated? (5)

Answer 23

A whole host of crap.
Histamine
TNF & other cytokines
Proteases
Heparins
Membrane-derived lipid mediators of inflammation

Question 24

Histamine causes…. (3)

Answer 24

INFLAMMATION
vasodilation
oedema
formation of INF in tissues

Question 25

What is usually produced on demand but mast cells store them for jokes?

Answer 25

Cytokines

Question 26

Proteases causes...

Answer 26

tissue remodelling

Question 27

Heparins causes...

Answer 27

we don't know, but we think they might have a protective role

Question 28

TNF & other cytokines released by mast cell degranulation cause

Answer 28

inflammation and tissue growth

Question 29

Do antihistamines work for asthma?

Answer 29

No.

Question 30

What is the difference between lung mast cells and skin/connective tissue mast cells? Both contain....

Answer 30

In the lungs there is little histamine. In the skin/connective tissue there is more histamine, heparin, chymotryptase. Both contain tryptase.

Question 31

Membrane-derived lipid mediators of inflammation include (3)

Answer 31

Leukotrienes Prostaglandins PAF (platelet aggregating factor).

Question 32

How is arachidonic acid produced?

Answer 32

membrane phospholipid + PLA2

Question 33

What does arachidonic acid get metabolised into (2) ... via.... (2)

Answer 33

Prostaglandins (via COX) | Leukotrienes (via 5-lipoxygenase)

Question 34

What leukotrienes are produced in mast cells? (is asthma)

Answer 34

LTB4, LTC4, LTD4

Question 35

What does LTB4 do?

Answer 35

Chemotactic to leukocytes | no direct bronchoconstriction

Question 36

What does LTC4 do?

Answer 36

potent constriction of airway smooth muscle | increase vascular permeability

Question 37

What does LTD4 do?

Answer 37

potent constriction of airway smooth muscle | increase vascular permeability

Question 38

What prostaglandins are produced by mast cells? (in asthma)

Answer 38

PGE2 and PGD2

Question 39

What does PGD2 do?

Answer 39

chemotactic and bronchoconstrictor

Question 40

What does PGE2 do?

Answer 40

relaxes airway smooth muscle may decrease leukocyte activation sensitised irritant receptors - cough

Question 41

3 overall effects of inflammation in asthma?

Answer 41

Oedema - increased secretion causing occlution of airways Dilation of bronchial vessels - reddening Leukocyte infiltrations (eosinophils and T-lyphoctes)

Question 42

Numbers of what cells increase 50 fold in asthma?

Answer 42

eosinophils | also increase 5 fold in atopic non-asthma

Question 43

What 3 groups stimulate eosinophils?

Answer 43

Cytokines Lipid mediators (LTB4, PAF) Chemokines (eotaxin)

Question 44

Products of eosinophils (4)

Answer 44

Lipid mediators - bronchoconstrict & inflammatory ROS Cationic products Cytokines

Question 45

What is the effect of having ROS

Answer 45

damage to epithelium

Question 46

What is the effect of cationic proteins?

Answer 46

Damage to endothelium and M2 receptor antagonist

Question 47

e.g. of cationic proteins

Answer 47

Major basic protein (MBP) Eosinophil cationic peptide (ECP) Eosinophil peroxidase (EPO) Eosinophil derived neurotoxin (EDN)

Question 48

Which cationic protein antagonises M2?

Answer 48

Major basic protein (MBP)

Question 49

Do non allergic asthmatics reactic to the skin test?

Answer 49

No

Question 50

Atopic is extrinsic or intrinsic?

Answer 50

Extrinsic - i.e. allergic

Question 51

How does the innate immune system cause production of IL13

Answer 51

Virus stimulates Epithilial cells and alveolar macrophages These produce IL33 This stimulates natural helper cells to produce IL13 Bypasses the T cells of the specific immune system

Question 52

Action of IL 13

Answer 52

Increased eosinophil adhesion and migration Tissue remodeling Increases airway contractility Increases mucus secretion (In allergic disease: Th2 skewing & switches B cells to produce IgE)

Question 53

Overall in asthma what do inflam mediators do to smooth muscle?

Answer 53

contract | growth

Question 54

Overall in asthma what do inflam mediators do to leukocytes

Answer 54

chemotaxis | activation

Question 55

Overall in asthma what do inflam mediators do to epithelium

Answer 55

damage | scarring

Question 56

Overall in asthma what do inflam mediators do to bronchieal venules

Answer 56

increased permeability blood flow leukocyte adhesion