Hypersensitivity reactions (asthma and allergy)

Question 1

What is hypersensitivity and what are the 4 types?

Answer 1

An inappropriate immune response to non-infectious antigens that results in tissue damage and disease - Type 1: immediate hypersensitivity Type 2: cytotoxic hypersensitivity Type 3: serum sickness and Arthus reaction Type 4: delayed-type hypersensitivity, contact dermatitis

Question 2

What is the arthus reaction and what occurs as a result?

Answer 2

The Arthus reaction is a rare adverse reaction that usually occurs after vaccination with large and more severe local reactions, belonging to type Ⅲ hypersensitivity reaction Antigen injected into the arm, excess of antigen as a result. This results in the formation of immune complexes. Immune complexes activate complement which in turn activates mast cells. inflammatory cells invade the site, and blood vessel permeability and blood flow are increased. Platelets also accumulate, leading to occlusion of the small blood vessels, haemorrhage, and the appearance of purpura.

Question 3

What is the serum sickness?

Answer 3

caused by large intravenous doses of soluble antigens (e.g. drugs) IgG antibodies produced form small immune complexes with the antigen in excess. immune complexes deposited in tissues e.g. blood vessel walls. tissue damage is caused by complement activation and the subsequent inflammatory responses

Question 4

Summary photo of the 4 types of hypersensitivity

Answer 4

see photo and also see Nicolas sheet of summary page

Question 5

What 2 phases does an allergic respose have and what mediates each phase?

Answer 5

• Allergic responses have an early and late phase
• Early is mediated by mast cells
• Late is mediated by T cells

Question 6

What effector mediators are produced by mast cells and what effect do they have?

Answer 6

Early phase:

Histamine-

increase vascular permeability

cause smooth muscle contraction

Leukotrienes-

increase vascular permeability

cause smooth muscle contraction

stimulates mucus secretion

Prostaglandins-

chemoattractants for T cells,

eosinophils and basophils

Late phase:

Cytokines:

IL-4 promotes Th2

IL-23 promotes IgE

TNF-alpha promotes tissue inflammation

Question 7

What are some properties of eosinophils and what effector functions do they have?

Answer 7

Eosinophils:

located in the tissues

recruited to the sites of allergic reactions

express FceRI upon activation

The two effector functions of eosinophils:

1. Release highly toxic granule proteins and free radicals upon activation to kill microorganisms/parasites and cause tissue damage in allergic reactions.
2. Synthesise and release prostaglandins, leukotrienes and cytokines in order to amplify the inflammatory response by activating epithelial cells and recruiting leukocytes.

Question 8

A summary of how an allergy develops

Answer 8

• There is a key difference between sensitisation to allergen and reaction to allergen.
• Individuals must be sensitised to an allergen before they can react.
• Sensitisation requires presentation of allergen to T cells by Dendritic Cells and the priming of Cognate B cells 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 9

What is asthma?

Answer 9

•“A State of reversible bronchial hyper-reactivity resulting from a persistent inflammatory process in response to a number of stimuli in a genetically susceptible individual”.

•

•Atopic and Non-Atopic

–Non Atopic includes

• Occupational
• Exercise induced
• Nocturnal Asthma
• Post-bronchiolitic Wheeze

Non-allergic asthma, or non-atopic asthma, is a type of asthma that isn’t related to an allergy trigger like pollen or dust, and is less common than allergic asthma. The causes are not well understood, but it often develops later in life, and can be more severe.

Question 10

What is allergic asthma?

Answer 10

•“A State of reversible bronchial hyper-reactivity resulting from a persistent inflammatory process in response to a number of stimuli in a genetically susceptible individual”.

•

•Atopic and Non-Atopic

–Non Atopic includes

• Occupational
• Exercise induced
• Nocturnal Asthma
• Post-bronchiolitic Wheeze

Question 11

How is allergic asthma characterised?

Answer 11

Characteristics:

episodes of wheezy breathing

narrowing of the airways

rapid changes in airway

obstruction

severity varies

• slight wheeziness to asthma

attack

common allergens causing

asthma include

pollen

HDM

plants

some foods

Question 12

What is the acute response to allergic asthma?

Answer 12

Acute response:

occurs within seconds of allergen exposure

results in airway obstruction and breathing difficulties

caused by allergen-induced mast cell degranulation in the

submucosa of the airways

Question 13

What is the chronic response in allergy asthma?

Answer 13

Chronic response:

chronic inflammation of the airways 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

Question 14

What are some treatments of allergy?

Answer 14

Blockage of effector pathways:

inhibit effects of mediators on specific receptors:

anti-histamine (block the histamine H1 receptor)

inhibit mast cell degranulation:

mast cell stabilizer (e.g. chromoglycate)

inhibit synthesis of specific mediators:

lipoxygenase inhibitors (e.g montelukast)

BUT MOSTLY we use:

Steroids – Act directly on DNA to increase transcription of anti-inflammatory mediators (e.g. IL-10) and decrease transcription of pro-inflammatory mediators (e.g prednisolone)

Bronchodilators – Reverse acute effect of allergy on airways (e.g B2 agonist salbutamol)

Immunotherapy – Reverses the sensitisation to allergen by means of tolerising exposure