IMMUNO: Allergy Flashcards
What is the difference in triggers of Th1/Th17 and Th2 immune responses?
Th1/17 is the immune reponse to bacteria/fungi/viruses
Th2 is to parasites, venoms and allergens.
Name the signalling an effector cytokines in Th2 immune memory responses. What are the sensors and effectors in this reaction?
Give an overview of the Th2 immune responses.
- Stressed or damaged epithelium will release signalling cytokines (e.g. TSLP / Thymic Stromal Lymphopoietin)
- Cytokines act on Th2, Th9 and ILC2 (Innate Lymphoid Cells T2) à promote the section of IL4, IL5 and IL13
- IL-4 acts on both pathways
- IL-4 stimulates B-cells to produce IgE and IgG4
- These then act on eosinophils and basophils which plays a role in the expulsion of parasites and allergens but can also contribute to tissue injury
- The TSLP and other cytokines released by the damaged epithelium can also activate follicular Th2 cells which then releases IL4 (n.b. cDC2 = Classical Dendritic Cell 2)
Why have allergic disorders risen over the past 150 years?
Many theories:
Hygiene hypothesis: lack of childhood exposure to infectious agents increases susceptibility to allergic diseases by supressing natural development of immune system.
Increase in epithelial-damaging agents linked to industrialisation, urbanisation and modern lifestyle.
Loss of symbiotic relationship with bacteria with reduction in biodiversity and alteration in composition of composition of gut skin and respiratory bacteria
Other factors:
- Shift to indoor lifestyle and increased exposure and sensitisation to perennial indoor allergen (asthma)
- Change in food processing and preparation
- Delayed introduction of peanuts in children with egg allergy and atopic dermatitis
What is throught to be the cause behind allergic rhinitis?
Link with pollen made in 1870 however still a rare disease although by 1900 well recognized in higher income groups and epidemic in New York in 1940.
Clean water, improved food hygiene, eradication of helminths, limited exposure to farm animals and soil bacteria smaller family size, (all components of hygiene) were achieved by 1920’s in major urban centres
Changes in farming practices late 19th century: increased dairy herds, introduction of rye grass ( generate more pollen) important for rise in grass pollen rhinitis
Give a piece of evidence that microbial environment can protect against asthma.
Comparing Amish and Hutterite communities
- They share similar genetic background yet have different lifestyles
- Prevalence of asthma and sensitisation much lower in Amish than in Hutterites
- Increase in LPS in dust samples collected from Amish than Hutterites
- Increased secretion of innate immune cytokine by PBMC exposed to LPS in Amish than Hutterites
- Dust samples from Amish suppress allergic inflammation in a murine asthma model
When did food allergy rise? What is the difference in reaction to roast and boiled peanuts?
1990 onwards: Significant increase in number of cases of peanut allergy attending allergy clinics in the UK and the USA
Early oral exposure will protect against development of peanut allergy
Sensitisation to peanut and wheat can occur from exposure through the skin
Differences in preparation of peanuts (roast promotes IgE whereas boiled IgG)
Epidemic of delayed food allergy to red meat observed in SE USA for last 10 years: increasing case in France, Germany, Australia but not in UK to date)
How is allergic disease diagnosed?
History is the key to diagnosis
Examination
Allergen specific IgE (Sensitisation) Tests - (1) Skin prick and intradermal test (2) IgE blood tests
Functional allergen tests
In vitro tests
- Basophil activation
- Serial mast cell tryptase
Ex vitro tests
- Open or blinded allergen challenge
What is the difference in allergy types with age?
Infants
- Atopic dermatitis
- Food allergy (milk, egg, nuts)
Childhood
- Asthma (HDM, pets)
- Allergic rhinitis (HDM, grass, tree pollens)
Adults
- Drug allergy
- Bee allergy
- Oral allergy syndrome
- Occupational allergy
What are the clinical features of IgE allergic responses?
Occurs within minutes or up to 3-4 hours after exposure to allergen
SYMPTOMS
- Skin: angioedema (swelling of lips, tongues, eyelids) , urticaria ( wheals or ‘hives’), flushing and itch
- Respiratory tract: cough, SOB wheeze, sneezing, nasal congestion and clear discharge, red itch watery eyes
- Gastrointestinal tract: nausea, vomiting and diarrhoea
- Blood vessels and Brain: symptoms of hypotension (faint, dizzy, blackout) and a sense of impending doom
What other cofactors can help induce anaphylaxis?
nexercise, alcohol, NSAID and in children viral infection
Where can link between exposure and onset of symptoms not be obvious?
- House dust mite
- Fungal and Staph skin colonisation
- Red meat ingestion
What is a clinical feature of allergy upon rexposure?
- At least 2 organ systems are usually involved.
- Reproducible: occurs after every exposure
Is IgE presence necessary for diagnosing allergic disease? What marker in addition is better for diagnosing allergic disease?
Necessary but not suffifient for its diagnosis
IgE is best considered a risk factor for allergic disease as it is most commonly associated with sensitisation which is generally more common
In the context of an appropriate history larger skin wheals and higher specific blood IgE values are more likely to be associated with allergic disorder
Do results of skin prick or IgE in serum predict severity of reaction?
No