Immunology 3 - Allergy

Question 1

Which CD4+ T cell subsets can recognise the conserved structures in pathogens? (PAMPS)

Answer 1

Th1 and Th17

Question 2

How does the immune system recognise and respond to allergens?

Answer 2

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

Question 3

Which other cell types promote the secretion of iL-4,5+13?

Answer 3

ILC-2 and Th9

Question 4

Which other cell type is activated in the allergen response?

Answer 4

TSLP, iL-33 etc also activate Tfh cells which activate B cells which then produce IgE

Question 5

Oral vs skin exposure to allergens - what is the difference?

Answer 5

Oral –> immune tolerance IgG + IgA response

Skin –> IgE production due to skin DCs being efficient at priming an Th2 reaction

Question 6

In Th2 immune memory response, which cell is the sesnor?

Answer 6

Mast cell

Question 7

Th2 immune memory response

Answer 7

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

Question 8

Which interleukin plays a crucial role in the development of Th2 immune response and when is it only induced?

Answer 8

IL-4, it is induced only folllwing peptide-MHC presentation to a naive/memory Th2 cell

Question 9

CD4 Th2 cells transcription factor

Answer 9

GATA3

Question 10

il4,il5,il13 functions

Answer 10

iL-4 –> B cells produce IgE
IL-5 –> expands and activates eosinophils
IL-13 –> mucous secretion

Question 11

Which interleukin is key in the development and expansion of eosinophils?

Answer 11

IL-5

Question 12

Is there currently a drug target for IL-33?

Answer 12

No

Question 13

What is the most and least common allergic disease in adults?

Answer 13

Most common: allergic rhinitis

Least common: food allergy

Question 14

What are the delayed symptoms of allergy caused by?

Answer 14

T2 cell (IL-4,5,13) responses and eosinophil related tissue damage

Question 15

What are some theories behind increasing prevalence of allergy?

Answer 15

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)

Question 16

clinical fx of an allergic response? Refer to 4 different systems

Answer 16

Skin - flush/angioedema/urticaria
GI - D+V
Resp: SOB, wheeze, cough
Vasculature sx: hypotension, impending doom 
(usually need at least 2)

Question 17

Relevant Ix for allergic disease

Answer 17

At time of reaction/acute = SERUM TRYPTASE

• Skin prick
• lab measurement of igE to specific allergen
• Component resolved diagnostics
• basophil activation tests
• challenge test

Question 18

Positive outcome a skin prick test?

Answer 18

Wheal >3mm

Question 19

What are positive and negative control in skin prick test?

Answer 19

+ve - histamine

-ve - diluent

Question 20

Disadvantages of skin prick test

Answer 20

stop antihistamines 48hrs before
High false positive
Anaphylaxis risk
Can’t use in extensive eczema or dermatographism

Question 21

Why is IgE RAST useful (serum specific IgE blood test)?

Answer 21

Can predict, depending on concentration of IgE, whether a child will outgrow allergy and can monitor anti-IgE therapy

Question 22

Indications for IgE RAST

Answer 22

Cnanot stop antihistamines
Hx of anaphylaxis
Dermatographism/extensive eczema
Borderline/equivocal SPT

Question 23

Describe component resolved diagnostics (CRD)?

Answer 23

Blood test to detect igE to SINGLE protein component

Heat and proteolysis stable proteins = severe allergy

Question 24

Gold standard Ix for FOOD AND DRUG ALLERGY?

Answer 24

Food allergen challenge test

Question 25

Which Ix should be done at time of allergic episode?

When is it at its peak?

Answer 25

Mast cell tryptase
Peaks at 1-2 hours
backt o baselines @6-12hrs

Question 26

Failure of baseline return of tryptase after 12 hrs?

Answer 26

Systemic mastocytosis

Question 27

What does a positive IgE test demonstrate?

Answer 27

It only demonstrates sENSITISATION, NOT clinical allergy - helpful to make diagnosis but NOT diagnostic

Question 28

Cause of hereditary angioedema

Answer 28

c1 esterase inhibitor deficiency

Question 29

DDx for anaphylaxis

Answer 29

Anxiety, panic
Endo: phaeo/carcinoid
C1 esterase inhibitor deficiency (hereditary angioedema)
ACEi induced angioedema and chronic urticaria
Severe asthma
CVS: MI, PE

Question 30

Diagnosis of anaphylaxis

Answer 30

Serial measurements of mast cell tryptase
Taken at 1, 3 and 24hrs
persistent rise in tryptase 24hrs after reaction = systemic mast celldisease

Question 31

Management of anaphylaxis

Answer 31

Raise legs
100% O2
IM adrenaline (1:1,000) - 500mcg
inhaled bronchodilators
100mg IV hydrocortisone
10mg IV chlorphenamine
IV fluids

Question 32

Adrenaline effect on receptors

Answer 32

A1 - peripheral vasoconstriction
B1 - increases HR, contractility and BP
b2 - Relaxes bronchial SM and reduces the release of inflammatory mediators

Question 33

Which drug +dose is given to prevent late phase response in acute anaphylaxis

Answer 33

IV 100mg hydrocortisone

Question 34

Which drug + dose is given to treat skin rash in anaphylaxis

Answer 34

IV 10mg chlorphenamine

Question 35

Food allergy vs food intolerance

Answer 35

Food allergy = specific immunological response, repeatable on exposure to specific food
Food intolerance = non-immune response e.g. food poisoning, lactose intolerance

Question 36

Describe food-associated, exercise-induced anaphylaxis, and the typical foods which cause it?

Answer 36

Ingestion of certain foods causes anaphylaxis if pt exercises within 4-6 hours of ingestion

Wheat, shellfish, celery

Question 37

Food allergy syndrome which is particularly associated with meat? What is the pathophysiology?

Answer 37

Delayed, food-induced anaphylaxis (meat and gelatin)

IgE against alpha1,3-galactose

aVOID TICK BITES

Question 38

Describe oral allergy syndrome’s pathophysiology

Answer 38

Limited to the oral cavity

Respiratory exposure to pollen –> cross reactivity with food (stone fruits, carrots, nuts)