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Infect & Immune 2 MW, NJH & AB > MW L2 Asthma & allergy > Flashcards

MW L2 Asthma & allergy Flashcards

1
Q

Allergy is what type of hypersentivity

A

Type 1

IgE mediated

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2
Q

What is allergy?

A

A change in reactivity

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3
Q

Not all asthmatics are allergic but what is similar?

A

Inflammation - mediators and cell content

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4
Q

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

A

atopic
young
less severe

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5
Q

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

A

Th2 cells

Th2 cytokines

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6
Q

Allergic people are often born…

A

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

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7
Q

Strongest link for developing allergy?

A

Genetic - parents with allergy

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8
Q

Th1 cells produce….

A

IFN gamma
OR
IL12

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9
Q

Th2 cells produce….

A 
IL2 and IL13 (similar/ overlap receptors)
OR
IL5
OR
IL9
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10
Q

What suppressed Th2 production?

A 
Th1 cytokines (and vice versa). 
Allergy is associated with imbalance of this
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11
Q

What cells become Th1 or Th2 cells?

A

Th0 - non-polarised cells

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12
Q

How does sensitisation to allergen occur?

A

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

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13
Q

Factors factoring the Th1 phenotype: (4)

A

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

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14
Q

Factors favouring Th2 phenotype: (5)

A 
Antibiotics
Western lifestyle
Urban
Diet
Dust mites and cockroaches
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15
Q

What makes IgE antibody?

A

Activated B cells

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16
Q

How does B cell become activated?

A

Th2 produces IL4 and IL13 which activate B cell.

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17
Q

What happens to IgE?

A

Binds to mast cells and waits like a detonator.

A second antigen exposure sets off reaction later.

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18
Q

Is IgE rare/common

A

Rare

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19
Q

What does E in IgE stand for?

A

‘Erythematous’

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20
Q

What region of IgE binds to what cells?

A

Fc region binds to FceR1

on mast cells and basophils

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21
Q

What causes degranulation of mast cells?

A

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

Binding arms it and cross linking produces degranulation.

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22
Q

Time course: initial sensitisation may take…

A

years

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23
Q

What does mast cells release when degranulated? (5)

A 
A whole host of crap.
Histamine
TNF & other cytokines
Proteases
Heparins
Membrane-derived lipid mediators of inflammation
24
Q

Histamine causes…. (3)

A

INFLAMMATION
vasodilation
oedema
formation of INF in tissues

25
Q

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

A

Cytokines

26
Q

Proteases causes…

A

tissue remodelling

27
Q

Heparins causes…

A

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

28
Q

TNF & other cytokines released by mast cell degranulation cause

A

inflammation and tissue growth

29
Q

Do antihistamines work for asthma?

A

No.

30
Q

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

A

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

31
Q

Membrane-derived lipid mediators of inflammation include (3)

A

Leukotrienes
Prostaglandins
PAF (platelet aggregating factor).

32
Q

How is arachidonic acid produced?

A

membrane phospholipid + PLA2

33
Q

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

A

Prostaglandins (via COX)

Leukotrienes (via 5-lipoxygenase)

34
Q

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

A

LTB4, LTC4, LTD4

35
Q

What does LTB4 do?

A

Chemotactic to leukocytes

no direct bronchoconstriction

36
Q

What does LTC4 do?

A

potent constriction of airway smooth muscle

increase vascular permeability

37
Q

What does LTD4 do?

A

potent constriction of airway smooth muscle

increase vascular permeability

38
Q

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

A

PGE2 and PGD2

39
Q

What does PGD2 do?

A

chemotactic and bronchoconstrictor

40
Q

What does PGE2 do?

A

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

41
Q

3 overall effects of inflammation in asthma?

A

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

42
Q

Numbers of what cells increase 50 fold in asthma?

A

eosinophils

also increase 5 fold in atopic non-asthma

43
Q

What 3 groups stimulate eosinophils?

A

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

44
Q

Products of eosinophils (4)

A

Lipid mediators - bronchoconstrict & inflammatory
ROS
Cationic products
Cytokines

45
Q

What is the effect of having ROS

A

damage to epithelium

46
Q

What is the effect of cationic proteins?

A

Damage to endothelium
and
M2 receptor antagonist

47
Q

e.g. of cationic proteins

A

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

48
Q

Which cationic protein antagonises M2?

A

Major basic protein (MBP)

49
Q

Do non allergic asthmatics reactic to the skin test?

A

No

50
Q

Atopic is extrinsic or intrinsic?

A

Extrinsic - i.e. allergic

51
Q

How does the innate immune system cause production of IL13

A

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

52
Q

Action of IL 13

A

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

53
Q

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

A

contract

growth

54
Q

Overall in asthma what do inflam mediators do to leukocytes

A

chemotaxis

activation

55
Q

Overall in asthma what do inflam mediators do to epithelium

A

damage

scarring

56
Q

Overall in asthma what do inflam mediators do to bronchieal venules

A

increased permeability
blood flow
leukocyte adhesion

Infect & Immune 2 MW, NJH & AB (12 decks)

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