Allergy Flashcards
What is an allergic disorder?
Immunological process resulting in immediate and reproducible symptoms after antigen exposure
What is an allergen?
A harmless substance that triggers an IgE mediated immune response and causes clinical symptoms
What is sensitisation?
Detection of specific IgE by testing (skin prick/in vitro blood test)
What does sensitisation show?
RISK of allergic disease
does NOT define allergic disease
So NECESSARY but NOT sufficient to cause allergy
What do allergens/venoms/helminths activate?
Cytokines:
- IL-1alpha
- IL25
- IL33
- TSLP
What do allergen cytokines activate?
Th2 cells (MAINLY)
Th9
ILC2
What are the Th2 effector cytokines?
What do they activate?
IL4
IL5
IL9
IL13
They activate eosinophils and basophils
Explain the tfh2 cell pathway
allergen > signalling cytokines > Tfh2 > IL4, IL21 > B cells >IgE, IgG4 > IgE cross links mast cell > histamine, leukotriene, prostaglandin release
What do histamines, leukotrienes, prostaglandins act ion?
Endothelium > increase permeability
Smooth muscles > smooth muscle contraction
Neurons>itching
What is a risk factor for IgE antibody development / sensitisation ?
Skin defect e.g. atopic dermatitis
as it allows allergen entry
Skin dendritic. cells promote Th2 cytokine secretion much more efficiently than other dendritic subtypes
What kind of exposure induces immune tolerance?
oral exposure
How does oral/Gi exposure promote immune tolerance?
Because Tregs from the GI mucosa inhibits IgE synthesis
What is the function of eosinophil?
Host defence against parasites, bacteria, viruses
What is the key cytokine for eosinophil development and expansion?
IL-5
What is normal IgE function?
To protect against helminth and parasitic infection
What is an unwanted effect of IgE function?
mast and basophil degranulation, associated to immediate hypersensitivity reaction
What are the 2 subtypes of mass cells in humans?
MC tryptase T in skin
MC chemotryptase CT in airway
What is mast cell degranulation triggered by?
IgE/IgG receptors
G protein coupled receptors
Explain mast cell/basophil degranulation
Cross linking of bound IgE > histamine, leukotriene, prostaglandin release
mast cell degranulation leads to:
- recruitment of soluble proteins and inflammatory cells to site of infection
- increase in rate of lymphatic flow back to regional lymph nodes
- smooth muscle contraction in lungs, gut
Factors that promote IgE production
Antigen dose
length of exposure
physical properties of antigen (source, water solubility, carbohydrates, resistance to heat/digestive enzymes)
route of exposure
What is the order of age of onset for allergic diseases?
Infants: atopic dermatitis, food allerggy
Childhood: asthma, allergic rhinitis
Adults: drug allergy, bee allergy
what are the theories for increased prevalence of allergic disorders?
Hygiene hypothesis Increased childhood vaccination, exposure to antibiotics, lack of vitamin D in infancy Dietary factors Alteration in intestinal microbiome High concentration of dietary sugars
What are clinical features of IgE mediated response?
MIN 2 ORGANS INVOLVED
SYMPTOMS MUST BE REPRODUCIBLE
SKIN: angioedema, urticaria flushing, itching
RESP: cough, SOB, nasal congestion, wheeze, red watery eye
GI: nausea, diahrroea, vomiting, hypotension
What is evidence that the microbiomial environment can protect against asthma?
Amish vs Hutterite communities
Amish have lower asthma prevalence as there is higher LPS prevalence in dust samples in Amish homes
What co-factors can trigger allergic symptoms?
Exercise
Alcohol
NSAID
Viral infection
What allergen specific IgE (sensitisation) tests can you do?
Skin prick test (SPT)
Intradermal test
IgE blood test
What does a skin prick test do?
Exposes pt to allergen extract solution through skin prick on arm
Looks for cross linking of IgE on skin mast cells > degranulation > release of histamine and other inflammatory mediators
What controls do you use for a skin prick test?
POSITIVE control (histamine) NEGATIVE control (dilutent)
How do you identify a positive result in a skin prick test?
wheal >3mm greater than positive control
What should you discontinue before SPT?
antihistamines /antidepressants containing antihistamine
for 48h prior
how do intradermal test work?
same principle as skinprick
allergen is now injected into intradermal layer
When are intradermal tests indicated?
To follow up negative venom or drug allergy test
If SPT is negative but story is convincing
What is the benefit of SPT?
Excellent negative predictive value (no false neg)
What is the benefit of intradermal test?
Excellent positive predictive value (no false positive)
What are indications for IgE blood test?
No access to SPT/IDT Patient can't stop antihistamine Patient has dermatographism (skin can't be scratched) Patient has excessive eczema Hx of anaphylaxis Borderline SPT results
What is increased serum tryptase a marker for?
systemic degranulation of mast cells during anaphylaxis
When is it good to get a serum tryptase?
if anaphylaxis dx is uncertain e.g. during anasthesia pt becomes hypotensive with rash
What is a food allergy?
An adverse health effect arising from specific immune response that occurs reproducibly on exposure to a given food
What is a food intolerance?
non-immune reaction that includes metabolic, pharmacological, unknown mechanism
What is an important risk factor for food allergy in children?
Atopic dermatitis
Which investigation is best to CONFIRM anaphylaxis is occurring
Tryptase
how do tryptase levels in anaphylaxis change over time
peaks at 1-2h
back to baseline in 6-12h
what are allergy tests you can do as elective?
SKin prick Intradermal Allergen specific IgE Basophil activation test Challenge test
What are allergy tests you should do during acute episode?
Mast cell tryptase
Blood/urine histamine
– looks for evidence of mast cell degranulation –
