Hypersensitivity I

Question 1

Characteristics of hypersensitivity

Answer 1

An exaggerated response of the immune system to foreign antigen causing tissue damage
A characteristic of the individual concerned
Damage is mediated by the same attack mechanisms that mediate normal immune responses to pathogens
Mediated by the adaptive immune system
Cannot be manifested upon first contact with antigen but appears on subsequent exposure- sensitisation step
Allergy and hypersensitivity are use interchangeably

Question 2

Common to all types of hypersensitivity

Answer 2

Adaptive (T and B cell) immune response
Reactions occur only in sensitized individuals- generally at least one prior contact with the offending agent
Sensitization can be long lived in the absence of re-exposure (>10 years) due to immunologic memory
Antigen is a protein or is capable of complexing with protein (hapten)

Question 3

Type I characteristics

Answer 3

Immediate or anaphylaxis
IgE mediated
Target cell: mast cell
Mediators: histamine, leukotrienes etc.
Examples: hayfever, allergic asthma, allergic rhinitis, atopic dermatitis, urticaria, anaphylaxis
The propensity to make an IgE response to environmental antigens varies among individuals
Atopic individuals are those with an inherited predisposition to form IgE responses

Question 4

Sensitization

Answer 4

Antigen contact, typically low dose via mucous membranes (respiratory, GI), primary IgE production

Question 5

Elicitation/ re-exposure and reactions

Answer 5

Pre-formed IgE (allergen-specific) triggers mast cell activation
Mediator release immediate (mast cell degranulation) and then early and late phase synthesis of other inflammatory mediators
Reactions: can occur within seconds to minutes of exposure, severity ranges from irritating to fatal

Question 6

Atopy

Answer 6

A greater tendency in the clinical presentation of type 1 hypersensitivity occurring in subjects with a family history of one or other similar conditions
Atopic individuals may suffer wheal-flare skin reactions to the intra-dermal injection of common environmental allergens
Raised level of serum IgE indicative of the diagnosis of an atopic individual, although a normal IgE serum level does not exclude atopy

Question 7

Cutaneous reaction

Answer 7

Skin prick test- simple diagnostic test for allergy or type 1 hypersensitivity
Allergen introduced into skin intra-dermally leading to mast cell degranulation and a wheal and flare skin reaction

Question 8

Immediate and late phase reactions

Answer 8

Immediate phase reaction: wheal and flare reaction, lasts up to 30 minutes post injection; raised, red and itchy
Late phase reaction develops approximately eight hours later and persists several hours, painful lump

Question 9

Significance of skin prick test for atopy

Answer 9

Patients with a variety of atopic disorders show the classic wheal and flare response demonstrating that IgE is bound to skin mast cells even though allergic reactions may be elsewhere such as the nose or bronchi e.g. pollen exposure in environment is via respiratory tract

Question 10

Genetic factors and allergy

Answer 10

Some HLA link to specific allergens, e.g. 90% of all responders to a low MW (5KDa) allergen from ragweed are HLA-DR2
Higher frequency of HLA-B8 in the general allergic population
Environmental pollutants e.g. sulphur dioxide, diesel exhaust particulates may increase mucosal permeability to allergens

Question 11

Penicillin allergy

Type 1 hypersensitivity

Answer 11

Most important of allergies to drugs, greater than 1% of all ADRs
0.2% of people treated with penicillin will have a reaction upon first administration, 2% will upon second administration
0.01% of those treated experience anaphylaxis, about 1 in 10 will die
Antigenic determinants are degradation products of penicillins that bind to host proteins

Question 12

Symptoms of penicillin allergy- skin, respiratory, heart and vascular

Answer 12

Skin: generalised hives, itchiness, flushing, swelling of the lips, tongue or throat
Respiratory: shortness of breath, wheezes, low oxygen
Heart and vascular: coronary artery spasm, subsequent myocardial infarction or dysrhythmia, drop in blood pressure, loss of consciousness, shock

Question 13

Cephalosporin cross-reactivity

Answer 13

Approximate two fold greater chance of suffering allergic reaction to cephalosporin if individual has penicillin allergy
Incidence rate confounded by:
- non allergic ADRs reported as drug allergy
- penicillins produced by fermentation from a cephalosporin mould
- cross reactivity with penicillin is higher in first and second generation cephalosporin than third
- more cross-reactivity between cephalosporins than between cephalosporin and penicillin

Question 14

Hyposensitisation

Answer 14

Strategy to inject repeatedly small quantities of allergen
Results in an increase in IgG against allergen and corresponding fall in specific IgE against allergen
Used fro grass pollen and bee/ wasp venom

Question 15

Medications

Answer 15

Cromoglicate/ nedocromil- inhalation products, mast cell stabilisers
Leukotriene receptor antagonists
Antihistamines
Steroids