MW L2 Asthma & allergy Flashcards
Allergy is what type of hypersentivity
Type 1
IgE mediated
What is allergy?
A change in reactivity
Not all asthmatics are allergic but what is similar?
Inflammation - mediators and cell content
Extrinsic is associated with atopic/non-atopic?
Young/middle onset?
More severe airflow limitation?
atopic
young
less severe
Allergy is driven by …. cells and their products ……..
Th2 cells
Th2 cytokines
Allergic people are often born…
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
Strongest link for developing allergy?
Genetic - parents with allergy
Th1 cells produce….
IFN gamma
OR
IL12
Th2 cells produce….
IL2 and IL13 (similar/ overlap receptors) OR IL5 OR IL9
What suppressed Th2 production?
Th1 cytokines (and vice versa). Allergy is associated with imbalance of this
What cells become Th1 or Th2 cells?
Th0 - non-polarised cells
How does sensitisation to allergen occur?
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
Factors factoring the Th1 phenotype: (4)
Older siblings
Early exposure to daycare
TB, measles, hep A
Rural
Factors favouring Th2 phenotype: (5)
Antibiotics Western lifestyle Urban Diet Dust mites and cockroaches
What makes IgE antibody?
Activated B cells
How does B cell become activated?
Th2 produces IL4 and IL13 which activate B cell.
What happens to IgE?
Binds to mast cells and waits like a detonator.
A second antigen exposure sets off reaction later.
Is IgE rare/common
Rare
What does E in IgE stand for?
‘Erythematous’
What region of IgE binds to what cells?
Fc region binds to FceR1
on mast cells and basophils
What causes degranulation of mast cells?
Cross linking of FceR1 - bound IgE on mast cell surface.
Binding arms it and cross linking produces degranulation.
Time course: initial sensitisation may take…
years
What does mast cells release when degranulated? (5)
A whole host of crap. Histamine TNF & other cytokines Proteases Heparins Membrane-derived lipid mediators of inflammation
Histamine causes…. (3)
INFLAMMATION
vasodilation
oedema
formation of INF in tissues
What is usually produced on demand but mast cells store them for jokes?
Cytokines
Proteases causes…
tissue remodelling
Heparins causes…
we don’t know, but we think they might have a protective role
TNF & other cytokines released by mast cell degranulation cause
inflammation and tissue growth
Do antihistamines work for asthma?
No.
What is the difference between lung mast cells and skin/connective tissue mast cells?
Both contain….
In the lungs there is little histamine.
In the skin/connective tissue there is more histamine, heparin, chymotryptase.
Both contain tryptase.
Membrane-derived lipid mediators of inflammation include (3)
Leukotrienes
Prostaglandins
PAF (platelet aggregating factor).
How is arachidonic acid produced?
membrane phospholipid + PLA2
What does arachidonic acid get metabolised into (2) … via…. (2)
Prostaglandins (via COX)
Leukotrienes (via 5-lipoxygenase)
What leukotrienes are produced in mast cells? (is asthma)
LTB4, LTC4, LTD4
What does LTB4 do?
Chemotactic to leukocytes
no direct bronchoconstriction
What does LTC4 do?
potent constriction of airway smooth muscle
increase vascular permeability
What does LTD4 do?
potent constriction of airway smooth muscle
increase vascular permeability
What prostaglandins are produced by mast cells? (in asthma)
PGE2 and PGD2
What does PGD2 do?
chemotactic and bronchoconstrictor
What does PGE2 do?
relaxes airway smooth muscle
may decrease leukocyte activation
sensitised irritant receptors - cough
3 overall effects of inflammation in asthma?
Oedema - increased secretion causing occlution of airways
Dilation of bronchial vessels - reddening
Leukocyte infiltrations (eosinophils and T-lyphoctes)
Numbers of what cells increase 50 fold in asthma?
eosinophils
also increase 5 fold in atopic non-asthma
What 3 groups stimulate eosinophils?
Cytokines
Lipid mediators (LTB4, PAF)
Chemokines (eotaxin)
Products of eosinophils (4)
Lipid mediators - bronchoconstrict & inflammatory
ROS
Cationic products
Cytokines
What is the effect of having ROS
damage to epithelium
What is the effect of cationic proteins?
Damage to endothelium
and
M2 receptor antagonist
e.g. of cationic proteins
Major basic protein (MBP)
Eosinophil cationic peptide (ECP)
Eosinophil peroxidase (EPO)
Eosinophil derived neurotoxin (EDN)
Which cationic protein antagonises M2?
Major basic protein (MBP)
Do non allergic asthmatics reactic to the skin test?
No
Atopic is extrinsic or intrinsic?
Extrinsic - i.e. allergic
How does the innate immune system cause production of IL13
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
Action of IL 13
Increased eosinophil adhesion and migration
Tissue remodeling
Increases airway contractility
Increases mucus secretion
(In allergic disease: Th2 skewing & switches B cells to produce IgE)
Overall in asthma what do inflam mediators do to smooth muscle?
contract
growth
Overall in asthma what do inflam mediators do to leukocytes
chemotaxis
activation
Overall in asthma what do inflam mediators do to epithelium
damage
scarring
Overall in asthma what do inflam mediators do to bronchieal venules
increased permeability
blood flow
leukocyte adhesion
