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Question 1

what is skin prick testing

Answer 1

Detection of allergen-specific IgE in vivo:

Allergen extract applied as drops

Top layers of epidermis punctured with lancet

A wheal with flare response after 15 minutes is positive

Result needs interpretation in clinical context

Question 2

how to detect for an allergen-specific IGE in vitro using an elisa

Answer 2

• Plastics coated with purified allergen of interest. Incubate with patient serum
• IgE antibodies in sera of sensitised patient bind to allergens
• Immobilised IgE antibodies detected with polyclonal anti-IgE detection antibody

Question 3

what is the action of Nasal decongestants

eg oxymetazoline

Answer 3

Act on α1 adrenoreceptors to cause vasoconstriction
Only for short-term use
Topical and systemic

Question 4

what is the action of B2 agonists

Eg salbutamol

Answer 4

Act on lung B2 adrenoreceptors, cause smooth muscle relaxation

Question 5

what is the action of Epinephrine

Answer 5

Systemic adrenergic effects oppose vasodilatation and bronchoconstriction

Question 6

give 2 classes of drug that treats early-phase mediators

Answer 6

1-H1 Antihistamines

2-Leukotriene receptor antagonists

Question 7

give the name action and characteristics of a mast cell stabiliser

Answer 7

sodium cromoglycate
Reduce mast cell degranulation by unknown mechanism
Not orally absorbed – topical use only
Short half-life requires frequent dosing
Main benefit is steroid-free, but efficacy very poor

Question 8

what is a first and 2nd generation H1 antihistamine

Answer 8

1st generation eg chlorpheniramine
Considerable sedation, drug interactions

2nd generation eg cerizine, loratidine, desloratidine, fexofenadine
No/ minimal sedation, once-daily

Question 9

give an example of a leukotriene receptor antagonist

Answer 9

Only UK drug is Montelukast

Effective in reducing early allergic responses, but inferior to H1 antihistamines

Unlike anti-histamines, beneficial in chronic asthma, which is the main indication for their use

Question 10

what types of cells do corticosteroids work on

Answer 10

Steroids reduce immune activation by altering gene expression in numerous cell types, including T cells, B cells and cells of the innate immune system. Their onset of action is delayed and they must be taken regularly

Question 11

what is in the brown asthma inhaler

Answer 11

Inhaled

Eg beclamathosome, fluticasone

Question 12

what can be used to treat seasonal rhinitis

Answer 12

Nasal

Eg beclamathasone, mometasone, fluticasone

Question 13

what are the side effects of corticosteroids used orally, via nose, and topically

Answer 13

oral candida

nose bleeds

local skin thinning

Question 14

what is omalizumab

Answer 14

is a monoclonal antibody directed against IgE, used for atopic asthma (amongst other things)

it binds to free IGE decreasing cell-bound IGE (binds to Fc region)

decreses the expression of high-affinity receptors

decreases mediator release

decreases allergic inflammation & prevents excacerbation of asthma and reduces symptoms

Question 15

what is allergen specific immunotherapy

Answer 15

Allergen doses administered by subcutaneous injection or sublingually

Provide long-term protection

Mainly venom allergy and rhinitis

Multiple immunological effects:

Induce regulatory T cell responses to allergens

Reduce Th2 responses

Induce allergen-specific IgG antibodies

Reduction in mast cell responsiveness

Reduce allergen-specific IgE levels

Question 16

what is contact dermatitis

Answer 16

Sensitising agents are typically highly reactive small molecules which can penetrate skin

These react with self proteins to create protein-hapten* complexes that are picked up by Langerhans cells, which migrate to regional lymph nodes

The Langerhans cells process and present the antigen together with MHCII

In some susceptible individuals, the complexes are recognised as foreign

The activated T cells then migrate to the dermis

Question 17

what is haptenisation

Answer 17

*Hapten=small molecule which cannot produce an immune response by itself, but can bind to a protein to alter its immunogenicity

Question 18

what is the elicitation process of contact dermatitis

Answer 18

Chemokines recruit macrophages

Th1 cells secrete IFN gamma: increases expression of vascular adhesion molecules, activates macrophages

TNF alpha/ beta: local inflammation

Question 19

what is the hallmarker of Th1 T cells

Answer 19

TNF-gamma

Question 20

how does poison ivy irritate the skin

Answer 20

Pentadecacatechol is a poison ivy lipid that may cross the skin and modify intracellular proteins

These proteins are processed and presented with MHC1 to CD8 T cells which then cause contact dermatitis

Again, not everybody is susceptible

Historical reports suggest that native Americans would feed their babies poison ivy to generate tolerance

Question 21

what is patch testing

Answer 21

Antigen-impregnated patch placed on back

Nickel, chrome, cobalt, epoxy resin, lanolin etc

Results read after 2 days

Question 22

what is the difference between contact dermatitis and type 1 allergy

Answer 22

Clinical features-
Various features consistent with mast cell degranulation-
Eczematous skin reaction

Temporal aspects-
Closely follows exposure then improves fairly rapidly-
Delay between exposure and symptoms

Causative agent-
Almost always naturally-occurring protein or closely related to one-
Various, often synthetic molecules

Effector mechanism-
Allergen-specific IgE, mast cell degranulation-
Antigen-specific effector
Th1 cells

Assessment-
Allergy clinic – history, skin prick testing, serology for allergen-specific IgE-
Dermatology clinic (UK) or Allergy clinic (Europe), history and patch testing

Management-
Avoidance if possible, pharmacotherapy, immunotherapy-
Avoidance only

Question 23

what is the difference between skin prick testing and patch testing

Answer 23

Indication-
History suggestive of IgE-mediated allergy-
History suggestive of contact dermatitis

Test format-
Allergen extract drops applied to skin, skin punctured, read after 15 minutes-
Test antigen applied under occlusive dressing, read after 48 hours

Positive-
Wheal and flare response-
Eczematous reaction

Question 24

describe the Tuberculin skint test (TST) and what type of allergy is it

Answer 24

type 4
Used to determine EXPOSURE to TB
Chemoprophylaxis may be indicated to reduce risk of reactivation

Tuberculin injected intradermally (tuberculin=complex mixture of antigens derived from MTB)

Local inflammatory response evolves over 24-72 hours if previously exposed

Fairly poor test for active TB

Question 25

what is the mechanism of TST

Answer 25

• antigen is injected into subcutaneous tissue and processed by local antigen-presenting cells
• TH1 effector cell recognizes antigen and releases cytokines which act on vascular endothelium
• recruitment of phagocytes and plasms to site of antigen injection causes visible lesion

Question 26

how can you detect TB-specific Th1 cells in vitro

Answer 26

interferon gamma release assay (IGRA)

Question 27

what is the interferon gamma release assay (IGRA)

Answer 27

• MTB peptides added to blood in laboratory
• Antigen presenting cell presents peptides with MHC2 and secretes IL-12

then we can detect interferon gamma by 2 methods, ELISA:

-Negative control: no interferon gamma
Positive control: high interferon gamma
TB antigen: high interferon gamma

ELISPOT method: slide 62

Question 28

what happens to someone with previous TB exposure in the IGRA

Answer 28

Effector memory Th1 cells recognise antigen. Because this is a secondary immune response, they are ‘primed’ and release cytokines within this short timeframe

• with no previous TB exposure -No primed effector memory T cells specific for MTB. No interferon gamma produced in such a short timeframe