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Flashcards in L23 - Allergy COPY Deck (27)
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1

THE EARLY PHASE REACTION

i) what leads to rapid development of symptoms in allergic individuals?

ii) how quickly does this reaction develop after exposure? what does it result from? (which two cells are involved)

iii) define allergen 

iv) name two cells that produce allergen specific IgE antibodies 

v) label diagram 

i) exposure to allergens leads to symptoms

ii) occurs within seconds or minutes after exposure
- results from binding of allergens to pre formed IgE antibodies on the surface of mast cells and basophils 

iii) allergen = substance to which IgE antibodies may be produced 

iv) B cells and plasma cells

v) A - allergen specific IgE antibodies
B - FceR1 high affinity IgE receptor 

2

EVENTS THAT FOLLOW MAST CELL IGE LIGATION

i) what does IgE bind? what does this cause the IgE antibodies to do?

ii) what activates the mast cell? what happens to the intracellular portion of the receptor?

iii) name two things released from the mast cell when it degranulates 

i) IgE binds its specific allergen 
- this causes cross linking of IgE antibodies > clustering of FceR1 receptors

ii) cross linking of antibodies and clustering of Rs activates mast cell > intracell portion of R is phosphorylated

iii) mast cell releases histamine and tryptase 

3

DELAYED MEDIATORS - LEUKOTRIENES

i) what enzyme does inflammation from mast cell activation activate? what molecule does this lead to production of?

ii) which enzyme pathway produces leucotrienes?

iii) what molecule do LT have similar pharma effects to? give an example? what condition is this important in 

i) inflamm activates phospholipase A2 > arachadonic acid

ii) 5 lipoxygenase pathway > LTs

iii) LTs have a similar pharm effect to histamine eg smooth muscle contraction in asthma 

4

PHARMA EFFECTS OF MAST CELL MEDIATORS AND LTS

i) what effect do they have on the GI tract/airway/blood vessels? what does each lead to?

ii) what type of clinical test can be used to monitor this?

iii) what type of reaction is produced in the skin?

iv) what is seen in the nose and eyes?

v) what is seen in the lungs? how does peak flow change on antigen challenge? does this resolve quick or slow 

i) GI tract - increase fluid secretion and peristalsis
- causes expulsion of GI contents eg N+V

airway - bronchoconstriction/inc mucus secretion
- wheeze/cough/swelling and mucus secretion in nose

blood vessel - vasodilation and increased permeability
- increased fluid in tissues (swelling), inc lymph in LNs, increased cell and proteins in tissues

ii) use skin prick test

iii) see wheel and flare reaction in the skin

iv) nose = rhinitis (sneeze/discharge), eyes = conjunctivitis

v) see wheeze in the lungs 
- rapid decrease in peak flow around 30 mins post antigen challenge which quickly resolves 

5

SOURCES OF ALLERGEN 

i) what type of allergens is IgE allergen generally mediated by?

ii) name three allergens that may be involved 

i) innocuous enviro proteins

ii) pollen, house dust mite faeces, stinging insect venom 

6

GENERAL CHARACTERISTICS OF ALLERGENS

i) what type of molecule are they almost always? what is the reason for this

ii) what physical property is favoured in these allergens? why? what is their usual solubility and mw?

iii) how homologous are they with self protein? why is this important?

i) almost always proteins - important as only protein can produce a T and therefore B cell response

ii) proteins that cross mucous membranes because they need to do this to activate immunity
- high solubility and low mw

iii) moderate homology to self protein
- low homology = wouldnt bind MHC
- high homology - would be deleted during neg selection

7

ANAPHYLAXIS

i) what type of reaction is it?

ii) what does systemic release of histamine cause? (2)

iii) name four classic symptoms assoc with skin, gut, mucosa, circulation 

iv) what are the three most common triggers in the UK?

v) how quickly does it occur post exposure? does it improve quick or slowly?

i) generalised allergic reaction

ii) generalised vasodilation and fluid loss from circ > tiss (swelling)

iii) skin - hives and angioedema
gut - vom and diarrhoea
mucosa - histamine release > laryngeal oedema and bconstric
circulation - vasodilat, hypoten and circ collapse

iv) most common triggers are food, drugs and insect venom

v) occ rapidly post exposure and improves quickly 

8

ORAL ALLERGY SYNDROME

i) what is it the most common type of in the UK?

ii) what is IgE directed against? what do these cross react with?

iii) what happens on exposure to raw fruit, nuts and vegetables

iv) what pollen mediates it most commonly in the uk? which fruits?

i) most common type of food allergy in adults

ii) IgE directed against pollen proteins 
- cross reac with homologous proteins in plant derived foods eg fruits

iii) exposure > oral itching

iv) pollen = birch
fruit = rosaecea fruit eg apple 

9

IGE MEDIATED AIRWAY DISEASE

i) give three symptoms of rhinitis

ii) give a symptom of lower airway obstruction

iii) name two seasonal allergens that may cause this? name two episodic causes?

iv) what type of symptoms cant be explained in terms of mast cell degranulation?

i) sneezing, rhinorhoea (runny nose), blockage

ii) wheeze

iii) seasonal - pollen/moulds
episodic - episodic/animal dander 

iv) when symptoms are chronic the inflam becomes established and cant be explained simply by mast cell degran

10

CHRONIC ALLERGIC INFLAMMATION - ASTHMA 

i) what duration of symptoms do these patients have?

ii) what are most patients sensitised to?

iii) what does biopsy of airways show? (2) what is this known as? what is seen in relation to the basement membrane and smooth muscle?

iv) what is found in the middle of the airway? what happens to goblet cells?

i) on going symptoms

ii) sensitised to a variety of airbourne allergens

iii) biopsy shows inflammatory infiltrate and airway changes
- known as remodelling
- see thickened basement membrane and smooth muscle hyperplasia

iv) mucus plug with trapped inflam cells in the middle
- goblet cells undergo metaplasia 

11

LATE PHASE ALLERGIC REACTION

i) what time frame does it occur after the early phase reac?

ii) what does biopsy of this phase principally show? name three specific cells seen 

iii) how is this measured? what happens to PEFR and how is this different to the early phase response?

iv) what main class of T cells are seen?

i) occurs hours after

ii) biopsy shows infiltration with allergy cells
- CD4 T cells, eosinophils and mast cells

iii) measured by giving an asthmatic patient an allergen and checking their peak flow
- late phase see a more gradual decrease in PEFR

iv) T helper 2 cells

12

T CELL SUBSETS AND TH2 HYPOTHESIS

i) name four interleukins that Th2 cells produce

ii) what have Th2 responses consistently been associated with? how has this been shown in vivo and in vitro?

iii) what is IL-4 required for? what do IL-4/13 promote? what is IL-5 req for? what does IL-9 recruit?

i) IL-4,5,9,13

ii) Th2 responses consistently associated with allergic disease
- in vivo - biopsy from allergic inflam are rich in Th2
- in vitro - T cells from allergic patients stimi;ated with allergen in the lab to produce Th2 cytokines

iii) IL-4 req for B cell class switch to IgE
IL-4/13 promote mucus hypersecretion
IL-5 req for eosinophil survival
IL-9 recruits mast cells 

13

CHRONIC ALLERGIC DISEASE - ASTHMA

i) what do inflammatory mediators cause in relation to mucus and smooth muscle? what does this lead to?

ii) name a cell that will be recruited from the circulation

iii) what leads to chronic disease? 

iv) what effect do IL-4,13,5,9 have?

v) what does this model suggest?

i) inflam mediators cause increased mucus secretion and smooth muscle contract > airway obstruc 

ii) recruit Th2 cells from the circ

iii) chronic disease caused by products released from Th2 cells

iv) IL4 - mucus hypersecretion
iL-13 - bronchial hyper-responsiveness
IL-5 - eosino recruit
IL-9 - mast cell recruit

v) model suggests a true role for T cells in chronic inflam rather than just causing IgE production 

14

GENETICS AND ALLERGY

i) what is childhood allergy strongly predicted by? 

ii) what is the main contributor in allergy?

iii) is allergy more common is HIC or LIC?

i) strongly predicted by presence of allergy in parents

ii) environment

iii) more in HIC 

15

HYGIENE HYPOTHESIS

i) what do low hygiene levels, high pathogen load and helminth infection skew immunity to and from? what cells may be induced?

ii) what do high hygiene levels, low pathogen load, absence of helminth infection skew immunity towards? what cells may be reduced?

 

i) low hygiene etc skews immunity from Th2 to Th1
- may induce regulatory T cells

ii) high hygiene levels etc skews immunity towards Th2 
- reduced production of regulatory T cells 

16

DETECTION OF ALLERGEN SPECIFIC IGE IN VIVO

i) what test can be used?

ii) what response is seen if there is a reaction? how long does this take?

iii) what is used as a positive and negative control? 

iv) is this diagnostic? why?

i) skin prick test

ii) see a wheal and flare response after 15 mins if positive

iii) positive = histamine
negative = dilutent

iv) not diagnostic as lots of false positives - needs interpretation in clinical context 

17

DETECTION OF ALLERGEN SPECIFIC IGE IN VITRO

i) what test used to be used? what is used now?

ii) explain the three steps - what happens if the patient is senitised to the allergen?

iii) what allows detection of a positive test?

i) used to use RAST now use ELISA

ii) well coated with purified allergen of interest
- incubate with patient seru,
- if patient is sensitised then IgE antibodies in the serum will bind the allergen 
- immobilised IgE antibod detected with polycolonal anti IgE detection antibody

iii) use of a detection antibody labelled with fluorescence 

18

TREATMENT OF ALLERGY - SYMPTOM RELIVERS

i) what do these act on?

ii) which receptors do nasal decongestants act on? what does this cause? how long should they be used for? give two methods of admin

iii) what receptor does salbutamol act on? what class of drug is it? what does it cause?

iv) what is adrenaline used to treat? what type of effects does it have? name two things it opposes? how is it usually admin?

i) acts on other pathways that oppose the actions of the mediators of the the allergy, not the mediators themselves

ii) nasal decongestants act on a1 adrenoreceptors 
- to cause vasoconstriction 
- only for short term use > topical and systemic admin

iii) salbutamol is an agonist at lung b2 adrenoreceptors 
- causes smooth muscle relaxation

iv) adrenaline is used to treat anaphylaxis 
- has systemic adrenergic effects
- opposes vasodilation and bronchoconstriction 
- give by IM injection 

19

TREATMENT OF ALLERGY - EARLY PHASE MEDIATORS

i) name a drug that works on histamine

ii) name a drug that works on leucotrienes

iii) what type of drug acts on mast cells? name a drug

iv) what do drugs that work on mast cells do? how must they be administered? how often do they need to be given? why?

v) what is the main benefit and disadvantage of these drugs 

i) H1 antihistamines

ii) leucotriene receptor antagonists

iii) mast cell stabilisers work on mast cells
- sodium cromoglycate

iv) mast cell stabilisers reduce mast cell degranulation by an unknown mechanism
- need be be given frequently as they have a short half life

v) main benefit is that they are steroid free but efficacy is very poor 

20

H1 ANTIHISTAMINES

i) what effect do they have at the H1 histamine receptor?

ii) when are they best used?

iii) name a first generation H1 antihist? name two disadvantages

iv) name a second generation anti hist? name two advantages

i) inverse agonists at the H1 histamine receptor

ii) best used before exposure to allergen 

iii) 2st gen = chlorpheniramine 
- sedation and drug interactions 

iv) second gen = loratidine
- no/minimal sedation and given once daily 

21

LEUCOTRIENE RECEPTOR ANTAGONISTS

i) what is the only licensed drug in this class in the UK?

ii) what are they effective in reducing? are they better or worse at this than H1 anti histamines?

iii) which condition are they most beneficial in? which drugs are not so beneficial here?

i) montelukast

ii) effective in reducing early allergic response but inferior to H1 anti histamines

iii) most beneficial in chronic asthma

22

TREATING ALLERGIC DISEASE WITH CORTICOSTEROIDS

i) what are steroid receptors complexed to in the cytoplasm before the binding of a steroid?

ii) what happens when the steroid binds its receptor? (3)

iii) what effect do steroids have on immune activation? how do they do this?

iv) how quickly is their onset of action? how often must they be taken?

i) complexed to heat shock protein hsp90 

ii) binds steroid > Hsp90 is released > steroid receptor complex crosses nuclear membrane to regulate gene expression

iii) steroids reduce immune activation by altering gene expression in different cell types eg T cells and B cells

iv) delayed onset of action and must be taken regularly 

23

CORTICOSTEROIDS

i) what can be used as a preventative inhaler?

ii) what can be used in a nasal spray?

iii) what can be used on the skin?

iv) name a side effect of opthalmic eye drops 

v) are oral preparations commonly used? when may an IV prep be used?

i) brown inhaler - beclamethosome 

ii) beclamathasome can be given in nasal spray

iii) hydrocortisone can be used on the skin

iv) SE of opthalmic eye drops is glaucoma therefore needs monitoring 

v) oral preps are toxic so not often used and IV preps are used in emergency 

24

OMALIZUMAB

i) what is it? what is it directed against?

ii) what is it mainly used for?

iii) what does it bind? and what does this lead to? 

iv) what happens to IgE receptors over time? what does this ultimately cause?

v) how quickly does it work? what type of allergy is it not useful in?

i) monoclonal antibody directed against IgE (binds the non antigen binding part of IgE) 

ii) mainly used for severe/atopic asthma

iii) binds to free IgE to form complexes which leads to less cell bound IgE in the circulation 

iv) over time there is decreased expression of high affinity IgE receptors which means IgE cant bind > less mediator release and allergic inflammation 

v) takes a while to work and not useful in food allergy 

25

ALLERGEN SPECIFIC IMMUNOTHERAPY

i) what is given to the patient? how is it given?

ii) what type of protection can it provide? which two allergies is it mainly used in?

iii) how does it affect regulatory T cells? Th2 responses? allergen specific IgG antibodies? mast cell responses? allergen specific IgE levels?

i) give patient large dose of allergen - subcut or sublingual

ii) can provide long term protection
- used in venom allergy and rhinitis

iii) induce Treg response to allergens
- reduces Th2 responses
- induces allergen specific IgG antibodies 
- reduction in mast cell responsiveness
- reduce allergen specific IgE levels 

26

CONTACT DERMATITIS (TYPE IV) VS TYPE I ALLERGY

i) what are the clinical features of each?

ii) how quickly are there symptoms after exposure in each? 

iii) what is the causative agent in each?

iv) what is the effector mechanism in each?

v) which clinic should assess each one?

vi) what type of management for each

i) type I - mast cell degranulation
type IV - eczematous skin reaction

ii) type I - quickly post exposure then resolves quick
type IV - delayed - due to T cell activation

iii) type I - naturally occuring molecules 
IV - synthetic molecules

iv) I - allergen specific IgE, mast cell degran
IV - antigen specific effector Th1 cells

v) I - allergy clinic
IV - dermatology clinic - patch test 

vi) I - avoidance, pharma, immuno therapy
IV - avoidance only 

27

SKIN PRICK VS PATCH TESTING 

i) what is each used for?

ii) what is the indication for each?

iii) what is the test format for each?

iv) what is seen in a positive test for each?

i) skin prick for IgE and patch for contact dermatitis

ii) skin prick if history is suggestive of IgE mediated allergy
patch - history suggest contact dermatitis

iii) skin prick - allergen drops applied to skin, puncuture, read after 15 mins
patch - tst antigen applied under dressing and read after 48 hrs

iv) pos test skin prick - wheal and flare
patch test - eczematous rash