Hypersensitivity reactions (asthma and allergy)

Question 1

What is type 1 hypersentitivity reaction?

Answer 1

Allergy

• Immune reactant = IgE
• Antigen = soluble antigen like allergen
• Effector mechanism involves mast cells which activate the process and hole the IgE on the surface
• Response - allergic rhinitis, asthma or anaphylaxis

Question 2

What is the wheel and flare reaction?

Answer 2

If you induce the response in a sensitized individual (injection of antigen)

If the mast cells has specific IgE for the presence of specific allergen = cross-linking of mast cells and activation causing vasodilation

Wheel - swelling and tissue odema

Flare - increased vasodilation

Eg. For a mosquito bite - you will see lump as wheel on skin

Question 3

What is type 2 cytotoxic hypersensitivty?

Answer 3

Caused by when you generate an immune response against a typical molecule which can become sensitized

• For example sticking to red blood cells surface proteins

Immune reactant = IgG (anti-drug antibodies)

• Some are directed at cell-surface receptors which disrupt the normal functions like in Grave’s disease or myasthenia gravis

Antigen = red cell or platelet that becomes coated with the drug

Effector mechanism - activates macrophages and complement resulting in the killing of those cells

Question 4

What is type 3 hypersensitivtity?

Answer 4

Immune reactant = IgG

Binds to soluble antigen

Effector mechanism - and form immune complexes which are cleared by phagocytes

Includes arthus reaction and serum sickness

Question 5

What is arthus reaction?

Answer 5

Typically occurs after a vaccination

Immune complexes activate complement which activates mast cells

Inflammatory cells invade the site and blood flow increases

Platelets also accumulate leading to occlusion of the small blood vessels, haemorrhage and appearance of purpura

Question 6

What is serum sickness?

Answer 6

Caused by large intravenous doses of soluble antigens

IgG antibodies produced form small complexes with the antigen in excess

The complexes are then deposited in tissues like blood vessel walls

Tissue damage is caused by complement activation and the subsequent inflammatory responses

Eg. Following antivenom from snakes

Question 7

What is type 4 hypersensitivty?

Answer 7

Delayed type

Question 8

What does Th1 do in delayed-type hypersnesitivty?

Answer 8

Question 9

What are some examples of type 1 allergy?

Answer 9

Drugs

Pollens

Dust-mite

Nuts

Food

Bites

Animal hair

Question 10

What is IgE?

Answer 10

• First line of defence against parasitic worms (also pollens and dust mite)
• Binds to mast cells high affinity receptor
• IgE allows mast cells to react when in presence of antigen

Question 11

How is IgE produced?

Answer 11

Il-4 tells the B cell to switch from IgG to IgE

Question 12

What causes allergic sensitisation?

Answer 12

Exposure to allergen is critical including:

• Nature of the allergen
• Dosage of the allergen
• Timing
• Location of priming

Role of pro-allergic dendritic cells and cytokines which will induce a Th cell to become Th2 cell, so B cells will produce IgE

Genetic predisposition to allergy

Question 13

What is filaggrin and atopic dermatitis?

Answer 13

Filaggrin links skin integrity and allergy

When it is defective atopic dermatitis is greater

This is due to the access for allergens

Question 14

What makes dendritic cell pro-allergic?

Answer 14

Question 15

What is the early and late phase allergic response?

Answer 15

Early - activation of mast cells by IgE - resulting in localised inflammation, short phase

Late - mediated by T cells, a prolonged phase

• Dependent on allergen dose

Question 16

What is released from the mast cell during the early and late phase?

Answer 16

Question 17

What are eosinophils?

Answer 17

• located in the tissues
• recurited to the sites of allergic reactions

1. Release highly toxic granule proteins and free redicals upon activation to kill microorganisms and cause tissue damage in allergic reactions
2. Synthesise and release prostaglandins and cytokines to amplify the inflammatory response

Question 18

How does allergy develop?

Answer 18

• Individuals must be sensitised to an allergen before they can react
• Sensitisation requires presentation of allergen to T cells by DC to produce IgE
• The reaction to allergen occurs when the individual is re-exposed to allergen and it binds preformed IgE on mast cells

Question 19

What is allergic asthma?

Answer 19

• Common allergens causing this includes: pollen, plants and some food
• Can be wheezing breathing, narrowing of airways, rapid changes in airway

Acute response

• Occurs within seconds
• Results in airway obstruction and breathing difficulties
• Caused by allergen-induced mast cell degranulation in the submucosa of the airways

Chronic response

• Caused by activation of eosinophils, neutrophils, T cells and other leukocytes
• Mediators released by these cells cause airway remodelling, permanent narrowing of the airways and further tissue damage

Treatment

• Anti-histamine
• Steroids
• Bronchodilators