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Respiratory System > Lung Immunology and allergic airway disease > Flashcards

Lung Immunology and allergic airway disease Flashcards

1
Q

List 3 allergic airway diseases

A

Divided into upper and lower airways:

Upper airways: allergic rhinitis
Bronchi: asthma
Alveoli: allergic alveolitis

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2
Q

What are the two different types of hypersensitivity reactions

A

Immunological
(“Allergy”)

Non-immunological

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3
Q

Describe immunological hypersensitivity reactions

A 
IgE-mediated
 atopic diseases
hayfever
eczema 
asthma

Non-IgE-mediated
allergic diseases
(e.g. Farmers lung

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4
Q

Describe non-immunological hypersensitivity reactions

A

Intolerance
(e.g.food)

Enzyme deficiency
(e.g.lactase DH def

Pharmacological
e.g. Aspirin hypersensitivity

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5
Q

What is allergy

A

Allergy is an exaggerated immunological response to a foreign substance (allergen) which is either inhaled, swallowed, injected, or comes in contact with the skin or eye.

Allergy is a mechanism (not a disease). Allergic mechanisms play an important role in some diseases all the time, and in others for some of the time.

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6
Q

Define allergy

A

An exaggerated sensitivity resulting from a heightened or altered reactivity of the immune system in response to external substances

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7
Q

Define hypersensitivity

A

Hypersensitivity-An umbrella term to describe an exaggerated sensitivity to any agent irrespective of the mechanism.

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8
Q

Describe the biphasic response to allergies

A

Type of response is important
Early- sneezing, eyes watering
later- nasal congestion

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9
Q

Describe type 1 immunity of mammals

A

Mammals protect themselves against viruses, bacteria, fungi and protozoa by mounting a type 1 immune response. This involves the recruitment of T helper type 1 (Th1) and Th17 cells, cytotoxic T cells, IgM, IgA and IgG subclasses.

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10
Q

Describe type 2 immunity of mammals

A

Type 2 immunity, on the other hand, protects against helminths (“worms”) and ectoparasites (“ticks”) and is mediated by Th2 cells, IgE and IgG1 antibodies as well as components of the innate immune system including epithelial barriers, innate lymphoid cells, eosinophils, mast cells, basophils and activated macrophages.

Cross-reactivity of IgE can cause allergies- dysregulation of IgE response

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11
Q

Outline the pathophysiology behind seasonal allergic rhinitis

A

1st step is sensitisation- allergen leaks through damages nasal mucosa/epithelia - already disrupted
Captured by a dendritic cell
Migrates to draining lymph nodes
Go to innate cells- such as ILC-2s
Help DC maturation and can help prime T cell into TfH or Th2
TfH can then prime B cells- proliferation and differentiation into plasma cells which express IgE
IgE bids to FceR receptors on mast cells and basophils
When the allergen crosslinks- degranulation- histamine release

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12
Q

What are the pro-allergic cytokines released by Th2 cells

A

IL-5,4 AND 13

There will also be lots of eosinophils (IL-5 is a survival factor for eosinophils)

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13
Q

What can we do in patients with allergic airway disease

A

Lung cell biopsy

Immunohistochemistry to challenged individuals- if allergic- lots of IL-4,5 + Th2 cells

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14
Q

Define atopy

A

Atopy – An hereditary predisposition to produce specific IgE antibodies to common aeroallergens

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15
Q

Describe atopy

A

Atopy is the hereditary predisposition to produce IgE
antibodies against common environmental allergens

The atopic diseases are allergic rhinitis, asthma and atopic eczema

Allergic tissue reactions (in atopic subjects) are characterised by infiltration of Th2 cells and eosinophils

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16
Q

Why do atopic conditions arise

A

Atopic (IgE-mediated) allergic conditions arise when individuals produce increased amounts of immunoglobulin E (IgE), a class of antibody which binds strongly to specific receptors (termed FcεR1 and FcεR2) found on mast cells (specialised cells found in connective tissue and airways), blood basophils and dendritic cells.

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17
Q

How does atopy differ to allergy

A

Sensitised but not allergic- they have the IgE antibodies in peripheral blood or skin-prick test (flare will be produced if allergic)
But exhibit no symptoms when exposed to the allergen

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18
Q

Describe ILC-2 cells

A

Like lymphocytes but have no TCR

Release IL-4 and IL-5

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19
Q

Describe the allergic march

A

Allergic march: food allergies from birth but need chronic (several seasons) exposure to develop allergic rhinitis
Idea: The ’allergic march‘ is the term describing the common progression of atopic diseases from atopic dermatitis to allergic asthma
hay fever can progress to asthma

20
Q

Describe the roles of different cytokines

A

o IL-4 à IgE synthesis.
o IL-5 à Eosinophil development.
o IL-9 à Mast cell development.
o IL-13 à IgE synthesis and airway hyperresponsiveness.

21
Q

Describe the epidemiology of allergic rhino-conjunctivitis

A

Allergic rhino-conjunctivitis
(Seasonal and perennial)
Up to 25% of the population

22
Q

Describe seasonal allergic rhino-conjunctivitis

A
  • Effects 12-15% children, 11-17% adults
  • UK prevalence highest in Europe
  • Effect on school exams, time off school
  • General effect on Q of L

THIS IS HAYFEVER.
§ Allergens vary from grass pollens, tree pollens, weed pollens and fungal pollens (the levels of which vary from season to season).

23
Q

What are the common causes of allergic perennial rhino-conjunctivitis and asthma

A 
o House dust mite. 
o Cats and dogs. 
o Alternaria (a form of fungus). 
o Cockroaches. 
o Horses.
Perennial means that it doesn't subside throughout the year
24
Q

What is special nowadays

A

Patients can be polysensitised and poly-allergic to different pollens and allergens from around the world- different patterns

25
Q

Describe the epidemiology of asthma

A

Asthma

Effects 8-12% of the population

26
Q

Summarise how we can categorise asthma based on its severity

A

§ Asthma is a very heterogeneous disease (many phenotypes):
o Intermittent, mild, allergy frequently important.
o Persistent, manageable, allergy often important.
o Chronic/severe, infection (not allergy) important.
§ Symptoms of asthma include cough, dyspnoea, wheezing, chest tightness and secretions (due to bronchoconstriction).

27
Q

Describe the different endotypes of asthma

A 
Early-onset allergic asthma (Th2-based)
Late-onset eosinophilic (IL-5 dominant. Allergy less pronounced)
Exercise induced (has a Th2 background)
Obesity-related (no biomarkers)
Neutrophilic (Th17/IL-8-related)

An “endotype” is proposed to be a subtype of a condition defined by a distinct pathophysiological mechanism.

28
Q

Describe the epidemiology of extrinsic allergic alveolitis

A

Extrinsic Allergic alveolitis

Effects 0.1% of the population

29
Q

Describe the mechanism of asthma

A 
Allergy is the usual trigger of an attack in early-onset asthmatics, and this is most commonly due to sensitivity to house dust mites or pollen. However, even in patients who suffer from allergic asthma, there are usually other triggers such as viral infections, exercise, exposure to fumes and other irritants such as tobacco smoke, and certain drugs (especially aspirin and related compounds). Food allergens and additives are rarely responsible but can also occasionally be implicated in triggering asthmatic symptoms. In a few cases, the role of allergy in asthma is obvious, such as in patients who wheeze when the pollen count is high but not at other times of the year. But in many cases it is difficult to determine the exact role of allergy in asthma.
Many asthmatics (about 25 per cent) have an eosinophilic phenotype but the role of allergy is often obscure. Their disorder often starts in later life and can be more severe than those who have asthma which begins in childhood.
30
Q

Describe the mechanism behind extrinsic allergic alveolitis

A

exposure to small allergenic particles that penetrate distal airways, captured by antibodies in the interstitium causing immunological cascades, complement and neutrophils/macrophages

  1. Small allergen particles enter the alveolus and pass into the interstitium.
  2. Allergic responses occur when antibodies bind to the allergens and stimulate a DTH response.
Antigen/antibody complexes
Complement
Chemotactic  factors
Neutrophils
Macrophages
Fibroblasts
31
Q

List some examples of extrinsic allergic alveolitis and their causative agents

A

Farmer’s Lung Mouldy Hay
Bird Fancier’s lung Bird Droppings
Air Conditioner lung Air conditioner moulds
Mushroom workers lung Mushroom compost
Malt workers lung Mouldy malt or barley
Coffee workers lung unroasted coffee beans
Millers lung infested flour
Hot tub lung Bacterial contamination

32
Q

Summarise the principles of treatment of allergic diseases

A

Allergen Avoidance
Anti-allergic medication
Immunotherapy (desensitisation/hyposensitisation

20% don’t respond to anti-histamines
can then take topical steroids
If these then don’t work- immunotherapy against specific allergen- need to have it for 3-5 years for it to work effectively

33
Q

Describe the symptoms of seasonal allergic rhinitis

A

runny nose, sneezing, congestion, leading to decreased productivity

34
Q

Describe the different categories of seasonal allergic rhinitis

A

mild intermittent
moderate, severe intermittent
mild persistent
moderate, severe persistent

35
Q

Describe allergen immunotherapy

A

The mode of action of specific immunotherapy is complex. IgG “blocking antibodies” that compete with IgE for allergen may prevent aggregation of FcεRI IgE complexes on mast cells through steric hindrance and as well as interfering with antigen trapping by IgE bound to antigen-presenting cells. Several studies have shown that specific immunotherapy inhibits the release of pharmacological mediators from mast cells and basophils, prevents infiltration of allergic lesions by inflammatory cells and decreases the number of tissue mast cells.
Central to these effects is the influence of specific immunotherapy on T lymphocyte function. There is evidence that specific immunotherapy induces a shift from a Th2 to a Th1 cytokine profile: production of IL-4 and IL5 decreases and the output of IFN-γ and IL-12 increases. These changes can explain the marked inhibition of the late-phase allergic reaction caused by immunotherapy. After several months or years of treatment the early, immediate weal and flare reaction and total serum IgE concentration are also reduced.

36
Q

Describe the other mode of action of immunotherapy

A

The induction of IL-10 secreting T regulatory cells also appears to be critical. IL-10 has a wide range of inhibitory effects on allergy, including the induction of long-term anergy in allergenspecific CD4+ cells, decreases the number of mast cells and inhibition of eosinophilopoiesis. It has been proposed that specific immunotherapy, as with other forms of immune modulation, may involve situations in which non-responsiveness induced (e.g. by IL-10) to one epitope of a molecule confers tolerance either to (i) the whole molecule (linked suppression), (ii) other molecules being presented by the same, or adjacent, antigen-presenting cells (bystander tolerance) or (iii) is passed to the next generation of naive T cells (infectious tolerance).

37
Q

Describe the difference between subcutaneous and sublingual immunotherapy

A

Subcutaneous- need to be monitored in clinic to protect against fatal anaphylactic reactions
Sublingual- totally safe to take at home - but not as effective as subcutaneous IT

38
Q

Describe the advantages and disadvantages of immunotherapy

A

Advantages
Effective
Produces long lasting immunity

Disadvantages
Occasional severe allergic reaction
Time consuming
Standardisation problems

39
Q

Summarise the immunotherapy mechanism

A

subcutaneous/sublingual exposure to traces of the allergen leads to desensitisation because TH cells become Tregs that inhibit TfH cells, stopping the producting of IgE antibodies; they can also cause B-cells to become Bregs that inhibit B-cells or become plasma cells that produce IgG/A antibodies that compete for allergen binding with IgE, reducing the hypersensitivity response

40
Q

Describe IL-35 in immunotherapy

A

Anti-inflammatory

Increased in Th1 response

41
Q

Describe the roles of Treg IL-35

A

Inhibits every step seen in how patients become allergic (earlier flashcard)

42
Q

Describe the functions of Bregs

A 
Suppression of Th1 cell differentiation 
Induce the differentiation of Foxp3+ Treg cells
Tr1 cell induction
Production of IgG4 Suppression of IgE
Suppression of TNF-α producing 
Suppression of Th2 immune response
43
Q

What is IgE binding dependant on

A

Nasal inhibitory activity for IgE-facilitated allergen Binding to B cells is IgG-dependent
With IgG4 cells- due to immunotherapy- less IgE binding- positive

44
Q

Why may allergens be on the rise

A

§ Factors could be microbial:
o Water sanitation (less oro-faecal infections).
o Food quality (lack of fermenting bacteria).
o Poverty (high asthma rates in urban).
o Medical intervention.
§ Factors could be non-microbial:
o Pollution (air, water, food).
o Diet and nutrition (lack of Vit-D, fish oil etc.).
o Obesity.
o Stress.
o Bad genes

45
Q

Describe the theories explaining why the prevalence of allergies may be increasing

A

§ The “hygiene hypothesis” – because the western environment is relatively clean, antibiotics are given out and due to vaccination, the immune system is deprived of the microbial antigens that stimulate TReg cells and and Th1 cells.
§ Gut flora may also have contributed to protection from atopic disease by releasing IL-10 which dampens the allergic response but with less gut flora, this may change.
§ IL-4, IL-5 and INF-gamma may all contribute to atopic responses.

46
Q

Define intolerance

A

Intolerance – The presence of symptoms following environmental exposure and/or food ingestion where an immunological mechanism cannot be established.

47
Q

Give an example of intolerance

A

Although many patients complain of abnormal reactions to food, few are caused by true IgE-mediated food allergy. When an allergic cause has been excluded by a careful clinical history and laboratory tests the condition is termed “food intolerance”. Examples of these are asthmatics who wheeze after exposure to food additives such as sulphites and nitrites. Here the mechanism is pharmacological/irritant rather than immunologica

Respiratory System (23 decks)

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