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Kendigs > Asthma immunopathogenesis > Flashcards

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

A

FeNO

25
Q

Recurrent infection with rhinovirus during preschool years associated with gene

A

SNPs in ORMDL3 gene (chromosome 17q)

26
Q

Genes in epithelium associated with high risk of asthma

A

IL-33
ProtoCADHERIN
CDHR3

27
Q

One of the BEST PREDICTOR of DEVELOPMENT OF ASTHMA from PRE school wheeze

A

Early alterations in smooth muscle function

28
Q

Viral vs multiple trigger wheeze

A

Viral wheeze, wheezing in discrete episodes, no symptoms in between
Multiple trigger wheeze, w/ symptoms during and in between

29
Q

Preschool vs school age in systemic steroids

A

No evidence of efficacy

30
Q

LRTA in preschool

A

Little benefit

31
Q

Also called INFECTION ASSOCIATED WHEEZE

A

Episodic viral wheeze

32
Q

Bronchoscopy studies of episodic wheezers during stable

A

Similar to nonwheezing
Predominantly NEUTROPHILIC
Associated with BACTERIAL cultures despite no symptoms

33
Q

Increased expression of IL-____ in submucosa has been reported in pre school MULTIPLE TRIGGER WHEEZERS

A

IL-4

34
Q

Only pathological abnormality predicting future asthma is

A

Airway smooth muscle

35
Q

Airway eosinophils (induced sputum) maybe used in adjusting the dose of inhaled ics

A

Preschool

36
Q

ICS on preschool

A

Improved exerbations
Less certain on lung function

37
Q

In children, NO relationship between airway hyperresponsiveness and ____

A

FeNO

38
Q

Mechanism on critical time window early life resulting in exaggerated eos

A

Lack of T regs in the 1st 2 weeks of life

39
Q

Growing up on a farm

A

Microbial and endotoxin impact epithelial innate immune system
Type 2 immnunity—> T reg cells

40
Q

MC pathogen during exacerbation
*defect in interferon with exaggerated Th2 response during viral induced asthma exacerbations

A

RHINOVIRUS

41
Q

Inflammatory infiltrate during exacerbation

A

Eos and neutrophils

42
Q

Prolonged duration of inflammation associated with

A

VIRAL LOAD

43
Q

In exacerbation, targeting airway eosinophil with ___

A

Systemic steroids

44
Q

Severe therapy resistant asthma pathologic profile:

A

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
Q

This cells are increased in STRA patients

A

Innate type 2 lymhoid cells

*fungal allergens — highest IL-33

46
Q

In STRA, it predicts increased severity

A

Early age onset
Allergen sensitization

47
Q

A specific feature that defines relative steroid resistance and more severe allergic disease

A

Fungal sensitization
*very high IgE
Need increased dose of steroids

48
Q

Improves steroid sensitivity
Inhibit IL 33 by enhancing the production of Receptor IL 33, soluble ST2

A

Vitamin D

49
Q

Vitamin d deficiency associated with

A

Increased eosinophlia
Inc Th2 cells
fewer CD4 IL 10 T regs

50
Q

How many % of children had severe asthma at school age with posssible airflow limitation by adulthood

A

50%

Kendigs (24 decks)

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