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Asthma immunopathogenesis Flashcards

1
Q

key component of asthma pathogenesis in children

A

allergic sensitization

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2
Q

Hallmark feature of the asthmatic immune response

A

Eosinophils

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3
Q

Role of Eosinophils in Allergic inflammation

A

INITIATION of events leading to Th2 inflammation
RECRUITMENT of TH2 cells to the lung

Suppression of TH1 mediated immunity

RELEASE of growth factors that contribute to the development of airway remodelling

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4
Q

Released by Th2 cells
Recruits EOSINOPHILS

A

IL-5

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5
Q

Predominant airway inflammatory phenotype
INDEPENDENT of severity and duration

A

Eosinophil

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6
Q

Blocks IL 5 survival
Increases eosinophic apoptosis
Reduction of airway eosinophilia

A

Glucocorticoids

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7
Q

Predominant mast cell mediators

A

HISTAMINE and Cysteine LEUKOTRIENES

HC

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8
Q

Responsible for bronchochonstriction, airway edema, inflammation

A

Degranulation of mast cells
Release of mediator
From binding of allergen specific IgE antibodies to mast cells

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9
Q

“M” odulates function of airway smooth muscle

A

“M”ast cells
Release of TH2 mediaters

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10
Q

Th2 mediator associated with airway hyperresponsiveness

A

IL-13

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11
Q

KEY inflammatory cell CENTRAL to driving asthma

A

Th2 lymphocyte or T helper 2

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12
Q

Th2 release what IL?

A

IL 4,5, 13

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13
Q

IL essnetial for develepment of Ig-E and allergic sensitization

A

IL 4

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14
Q

Secretes IL 17 and ROR-yT

A

Th17 from CD4

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15
Q

2 main types of Tregs in the lung

A

CD4 secreting IL-10 (decreased in SEVERE ASthma)

CD4 CD25 with Transcription factor Fox P3 (reduced in BAL of steroid naive asthmatic patients)

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16
Q

Steroid resistant asthma may be due to poor induction of

A

IL-10 from CD4

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17
Q

Innate cytokines

A

IL 33
IL 25
Thymic stromal lymphopoietic (TSLP)

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18
Q

Group 2 innate lymphoid cells secrete the Th2 cytokines IL4 IL5 IL 13 are induced by

A

IL-33 upon allergen exposure

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19
Q

Mediates severe therapy resistant asthma
Promotes airway remodelling
Steroid resistant

A

IL 33

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20
Q

Cells increasing during exacerbations

A

Neutrophils

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21
Q

Structural airway changes in children with asthma
*school age

A

INCREASE
Size, quantity of SMC
Number of vessels (angiogenesis)
Thickness of SUB epithelial RBM

22
Q

Switch in inflammatory phenotype may be due to

A

Acute respi infection
Eosinophilic to neutrophilic

23
Q

Non invasive biomarkers of eosinophlic inflammation
Closely related to PERIPHERAL blood eosinophils
Not used to monitor disease
May be associated with atopic dermatitis

A

SERUM EOS
CATIONIC PROTEIN

24
Q

Non invasive biomarker, Steroid sensitive
Associated with difficult asthma
Better marker
Adherence to steroids

Support diagnosis of asthma in steroid naive
Elevated in atopic NON asthmatic
Moderate diagnostic accuracy
Significant number of false positive, false negative

25
Recurrent infection with rhinovirus during preschool years associated with gene
SNPs in ORMDL3 gene (chromosome 17q)
26
Genes in epithelium associated with high risk of asthma
IL-33 ProtoCADHERIN CDHR3
27
One of the BEST PREDICTOR of DEVELOPMENT OF ASTHMA from PRE school wheeze
Early alterations in smooth muscle function
28
Viral vs multiple trigger wheeze
Viral wheeze, wheezing in discrete episodes, no symptoms in between Multiple trigger wheeze, w/ symptoms during and in between
29
Preschool vs school age in systemic steroids
No evidence of efficacy
30
LRTA in preschool
Little benefit
31
Also called INFECTION ASSOCIATED WHEEZE
Episodic viral wheeze
32
Bronchoscopy studies of episodic wheezers during stable
Similar to nonwheezing Predominantly NEUTROPHILIC Associated with BACTERIAL cultures despite no symptoms
33
Increased expression of IL-____ in submucosa has been reported in pre school MULTIPLE TRIGGER WHEEZERS
IL-4
34
Only pathological abnormality predicting future asthma is
Airway smooth muscle
35
Airway eosinophils (induced sputum) maybe used in adjusting the dose of inhaled ics
Preschool
36
ICS on preschool
Improved exerbations Less certain on lung function
37
In children, NO relationship between airway hyperresponsiveness and ____
FeNO
38
Mechanism on critical time window early life resulting in exaggerated eos
Lack of T regs in the 1st 2 weeks of life
39
Growing up on a farm
Microbial and endotoxin impact epithelial innate immune system Type 2 immnunity—> T reg cells
40
MC pathogen during exacerbation *defect in interferon with exaggerated Th2 response during viral induced asthma exacerbations
RHINOVIRUS
41
Inflammatory infiltrate during exacerbation
Eos and neutrophils
42
Prolonged duration of inflammation associated with
VIRAL LOAD
43
In exacerbation, targeting airway eosinophil with ___
Systemic steroids
44
Severe therapy resistant asthma pathologic profile:
Paucity of Th2 cytokines(high dose steroids no effect) Marke sensitization to MULTIPLE ALLERGENS Airway eosinipholia but NO INCREASE in tissue mast cells or neutrophils
45
This cells are increased in STRA patients
Innate type 2 lymhoid cells *fungal allergens — highest IL-33
46
In STRA, it predicts increased severity
Early age onset Allergen sensitization
47
A specific feature that defines relative steroid resistance and more severe allergic disease
Fungal sensitization *very high IgE Need increased dose of steroids
48
Improves steroid sensitivity Inhibit IL 33 by enhancing the production of Receptor IL 33, soluble ST2
Vitamin D
49
Vitamin d deficiency associated with
Increased eosinophlia Inc Th2 cells fewer CD4 IL 10 T regs
50
How many % of children had severe asthma at school age with posssible airflow limitation by adulthood
50%

Kendigs (24 decks)

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