6.3 Atopy, Anaphylaxis and the Immunology of Respiratory Disease Flashcards
Define Atopy
Genetic tendency to make allergic immune responses to common airborne allergens, and to develop allergic disease
Define “Allergy”
Adverse reaction to foreign substance (allergen) that is excessive/inappropriate and directed towards specific substances
Does an allergy require a previous encounter with the antigen?
Yes
Define sensitisation
Production of IgE antibodies in response to specific allergens
Is “allergy” the same as “sensitisation”?
No
At what point in someone’s life does atopy usually begin?
Infancy: dermatitis or eczema
List some environmental factors that are thought to have increased prevalence of allergic disease
- Tobacco smoke
- Air pollutants
- Diet
Th1 vs Th2 immune responses
Th1: Important for cellular immune response to pathogens
Th2: Important for immunity against helminths, implicated in pathogenesis of allergic disease
Explain how Th2 skewing can predispose to allergic disease. How does this fit in with the hygiene hypothesis?
- Th2 environment is skewed during gestation to promote tolerance of pregnancy
- In atopic individuals, this Th2 skewing persists after birth
- The hygiene hypothesis states that, due to increased sanitation, the environment remains Th2 skewed for longer, leading to more allergies
Cutaneous vs oral allergen exposure; which is more likely to cause allergy?
- Oral exposure is more likely to promote tolerance
- Cutaneous exposure is more likely to promote allergy
How early should allergens be introduced into food to prevent allergies?
Introduce allergenic foods by the age of 1
List some modern dietary changes that increase prevalence of allergic disease
- Lower fibre
- More omega 6 fats and less omega 3 fats
- Less fresh foods
- Higher saturated fats
Patient A takes folate during pregnancy to prevent neural tube defect. How can she make sure this is not likely to cause asthma and eczema in her unborn child?
Don’t take is in late pregnancy; only in early pregnancy
List three ways in which an infants microbiome can be influenced during pregnancy/birth
- Use of antibiotics during pregnancy
- Vaginal vs caesarian birth
- Mother’s microbiome during pregnancy
What is the predicted impact of prebiotics on unborn child microbiome
- Promotes growth of immunomodulatory microbiota
- Effects last in infants and adults
A child has asthma, and his mother is pregnant. How much more likely is the next child to have asthma?
3-4x more likely than usual.
Is allergic predisposition monogenic?
Not usually; it is mostly influenced by multiple genes, and is quite complex. There are rare monogenic causes
Is allergic disease high or low in prevalence in australia? Is it increasing or decreasing?
It is high, and it’s getting higher.
List three common causes of anaphylaxis
- Foods
- Medications
- Insects
List some uncommon causes of anaphylaxis
- Latex
- Cold temperature
- Immunisations
- Idiopathic
What substances are released during mast cell degranulation during an allergic reaction?
- Histamine
- Tryptase
- Prostaglandins
- Leukotrienes
- Cytokines
- Chemokines
List some consequences of an allergic reaction (i.e., what happens after mast cell degranulation?)
- Vasodilation
- Increased vascular permeability
- Inflammatory cell recruitment
- Mucus production
- Bronchoconstriction
Skin-based symptoms of anaphylaxis
- Hives
- Swelling
GI symptoms of anaphylaxis
- Vomiting
- Abdo pain
Respiratory symptoms of anaphylaxis
- Difficult/noisy breathing
- Swelling of tongue
- Swelling tightness in throat
- Difficulty talking and/or hoarse voice
- Wheeze or persistent cough
Cardiovascular symptoms of anaphylaxis
- Low blood pressure
- Persistent dizziness or collapse
- Pale and floppy (in young children)
Mild to moderate symptoms of allergic reactions
- Swelling of lips, face, eyes
- Hives or welts
- Tingling mouth
- Abdominal pain, vomiting
Under what circumstances do vomiting and abdominal pain become severe symptoms of anaphylaxis?
When they are brought about by an insect sting
Severe symptoms of anaphylaxis:
- Swelling of tongue
- Difficult/noisy breathing
- Persistent cough or wheeze
- Difficulty talking/hoarse voice
- Presyncope/syncope
What is urticaria?
Hives
Do skin complications have to occur during anaphylaxis?
No
In what age group do food-related anaphylaxis deaths almost always occur?
8-35 yrs
What is the most common cause of anaphylaxis deaths (i.e. what triggers the reactions)?
- Drugs (or probable drugs)
What is systemic mastocytosis?
Increased number of mast cells
List some risk factors for fatal anaphylaxis
- No adrenaline administration
- Upright posture during/after
- Asthma
- People with food allergy eating away from home/at restaurant
- Initial misdiagnosis
- Heart disease
- Systemic mastocytosis
Two most common causes of anaphylaxis (in order)
- Peanuts
- Treenuts
Are hypersensitivity reactions just for allergic responses?
- No
- They apply to a diverse range of immune responses
- They can be considered a framework to understand broader immune reactions
What type of hypersensitivity reaction is anaphylaxis?
Type 1
Describe type 1 hypersensitivity
- Initial exposure, Th2 cell prompts plasma cell to produce IgE antibodies, which bind to mast cell
- Upon secondary exposure, antigen cross links antibodies, leading to degranulation and hypersensitivity reaction
What type of hypersensitivity reaction is allergic rhinitis?
Type 1
What is cytopenia?
Low levels of RBCs
Describe type 2 hypersensitivity
- Antibodies bind to antigen on self cell (can be extrinsic or intrinsic)
- Activates complement, either causing immune cells to come and kill the self cell, or creating the membrane attack complex and killing the cell that way
Is type 1 hypersensitivity faster or slower than type 2?
Type 1 is faster; type 2 can take 2-7 days
Explain type 3 hypersensitivity reactions
- Antigen binds to antibody, forming immune complexes that are not large enough to trigger phagocytosis
- Deposited in tissues, triggering complement system and leading to inflammation
- Can damage blood vessels, and exacerbate local inflammatory response
How long does type 3 hypersensitivity take?
2-14 days
Describe typ2 4 hypersensitivity reactions
Immune reactions mediated by T cells (can be T helper cells or cytotoxic T cells)
Describe type 5 hypersensitivity, and give an example
- Antibody takes on the role of a messenger molecules
- Example: graves disease, where Thryoid stimulating immunoglobulin does the role of TSH, causing unregulated thyroid hypertrophy
List some atopic diseases
- Eczema
- Food allergy
- Asthma
- Allergic rhinitis
- Eosinophilic oesophagitis
Are all atopic disease driven through IgE mediated allergies?
- No
- For instance, eczema is not, but allergic rhinitis is
- There is a spectrum of IgE mediation
Allergic rhinitis mech
- Classic t1 hypersensitivity
- APC -> Th2 -> plasma cell -> IgE -> mast cell -> secondary exposure -> inflammation
Eczema mech
- Damage to skin
- Release of alarmins
- Dendritic cell activates T cell, which samples antigen from skin surface
- Activates B cell -> mast cell
- And activates eosinophil
-> perpetuates (allergen is bystander, not primary driver)
Name two treatment pathways for eczema. How do each of these work?
- Topical corticosteroids (reduce inflammation)
- Moisturisers (reduce initial damage)
How does immune tolerance induction help with allergies at a cellular level?
- Helps skew immune system back towards Th1 pathways, as well as Treg cell production that prevents overstimulation of the immune system
