Immunology 3 - Allergy Flashcards
Which CD4+ T cell subsets can recognise the conserved structures in pathogens? (PAMPS)
Th1 and Th17
How does the immune system recognise and respond to allergens?
Allergens release mediators e.g. proteases which disrupt epithelial barriers which is a functional change that is recognised by the immune system (damaged epithelium secretes TSLP, il-33 ETC) and gives rise to Th2 immune response. TH2 cells release cytokines IL-4,IL-5, IL-13
Activates basophils and eosinophils
Histamine and leukotrienes released
Which other cell types promote the secretion of iL-4,5+13?
ILC-2 and Th9
Which other cell type is activated in the allergen response?
TSLP, iL-33 etc also activate Tfh cells which activate B cells which then produce IgE
Oral vs skin exposure to allergens - what is the difference?
Oral –> immune tolerance IgG + IgA response
Skin –> IgE production due to skin DCs being efficient at priming an Th2 reaction
In Th2 immune memory response, which cell is the sesnor?
Mast cell
Th2 immune memory response
Allergen causes cross linking of IgE on mast cell –> release of histamine, leukotrienes, prostaglandins, they act on endothelium –> increased vascular permeability , smooth muscle contraction and neuronal itch
Response: expel allergen/parasite OR will be responsible for symptoms of asthma/hayfever/eczema
Which interleukin plays a crucial role in the development of Th2 immune response and when is it only induced?
IL-4, it is induced only folllwing peptide-MHC presentation to a naive/memory Th2 cell
CD4 Th2 cells transcription factor
GATA3
il4,il5,il13 functions
iL-4 –> B cells produce IgE
IL-5 –> expands and activates eosinophils
IL-13 –> mucous secretion
Which interleukin is key in the development and expansion of eosinophils?
IL-5
Is there currently a drug target for IL-33?
No
What is the most and least common allergic disease in adults?
Most common: allergic rhinitis
Least common: food allergy
What are the delayed symptoms of allergy caused by?
T2 cell (IL-4,5,13) responses and eosinophil related tissue damage
What are some theories behind increasing prevalence of allergy?
Hygiene hypothesis
Lack of vitamin D
Dietary factors (atleration in diversity of microbiome)
High concentration of dietary advanced glycation end-products and pro-glycating sugars which the immune system mistakenly recognises as causing tissue damage (e.g. fast food and soda)
clinical fx of an allergic response? Refer to 4 different systems
Skin - flush/angioedema/urticaria GI - D+V Resp: SOB, wheeze, cough Vasculature sx: hypotension, impending doom (usually need at least 2)
Relevant Ix for allergic disease
At time of reaction/acute = SERUM TRYPTASE
- Skin prick
- lab measurement of igE to specific allergen
- Component resolved diagnostics
- basophil activation tests
- challenge test
Positive outcome a skin prick test?
Wheal >3mm
What are positive and negative control in skin prick test?
+ve - histamine
-ve - diluent
Disadvantages of skin prick test
stop antihistamines 48hrs before
High false positive
Anaphylaxis risk
Can’t use in extensive eczema or dermatographism
Why is IgE RAST useful (serum specific IgE blood test)?
Can predict, depending on concentration of IgE, whether a child will outgrow allergy and can monitor anti-IgE therapy
Indications for IgE RAST
Cnanot stop antihistamines
Hx of anaphylaxis
Dermatographism/extensive eczema
Borderline/equivocal SPT
Describe component resolved diagnostics (CRD)?
Blood test to detect igE to SINGLE protein component
Heat and proteolysis stable proteins = severe allergy
Gold standard Ix for FOOD AND DRUG ALLERGY?
Food allergen challenge test
