Hypersensitivity and Allergy

Question 1

What are hypersensitivity reactions usually mounted against?

Answer 1

Harmless foreign antigens
Autoantigens
Alloantigens

Question 2

What are the four type of hypersensitivity reaction?

Answer 2

Type 1 – immediate hypersensitivity
Type 2 – antibody-mediated cytotoxicity
Type 3 – immune complex mediated
Type 4 – delayed cell mediated

Question 3

Describe the mechanism of type 1 hypersensitivity?

Answer 3

On 1st exposure you get sensitisation – IgE is produced, which binds to mast cells and basophils
On subsequent exposure, antigen cross-links the IgE on the mast cells causing degranulation and release of inflammatory mediators

Question 4

What types of diseases are examples of type 2 hypersensitivity?

Answer 4

Organ specific autoimmune diseases: e.g. myasthenia gravis, glomerulonephritis, pemphigus vulgaris, pernicious anaemia
Autoimmune cytopenias e.g. autoimmune haemolytic anaemia, thrombocytopenia, neutropenia

Question 5

What are the consequences of immune complex formation in type 3 hypersensitivity?

Answer 5

Immune complexes deposit in tissues and activate complement and cause cell recruitment
This can cause tissue damage

Question 6

Give some examples of diseases caused by delayed type hypersensitivity.

Answer 6

Chronic graft rejections
Graft-versus-host disease
Coeliac disease

Question 7

Describe the mechanism of delayed type hypersensitivity.

Answer 7

The transient/persistent antigen is presented to T cells, which then activate macrophages and CTLs
Activated macrophages produce TNF-alpha, which is responsible for much of the tissue damage

Question 8

What are three important cytokines released by Th2?

Answer 8

IL-4
IL-5
IL-13

Question 9

What is the difference between the antigens involved in type 2 and type 3 hypersensitivity?

Answer 9

Type 2 – insoluble antigens (cell surface or matrix bound antigens)
Type 3 – soluble antigens

Question 10

What is atopy?

Answer 10

A form of allergy in which there is a hereditary or constitutional tendency to develop hypersensitivity reactions in response to allergens

Question 11

How common is atopy?

Answer 11

Very common – about 50% of young adults in the UK

Question 12

List some genetic risk factors of atopy.

Answer 12

About 80% of atopics have a family history

The genetic component is polygenic but genes of the IL-4 cluster and genes on chromosome 11q have been linked to atopy

Question 13

Among which age group is atopy most common?

Answer 13

Teens

Question 14

Describe the gender difference in asthma

Answer 14

Males – asthma in childhood is more common

Females – asthma in adulthood is more common

Question 15

What other environmental factors affect atopy?

Answer 15

Family size, infections, animals, diet

Question 16

What type of hypersensitivity is responsible for anaphylaxis, urticaria and angioedema?

Answer 16

Type 1 hypersensitivity

Question 17

What type of hypersensitivity is responsible for chronic urticaria?

Answer 17

Type 2 hypersensitivity

Question 18

What type of hypersensitivity is responsible for asthma, rhinitisand eczema?

Answer 18

Type 1 and type 4 hypersensitivity

Question 19

Describe sensitisation in atopic airway disease.

Answer 19

T cells are naïve before they have seen their antigen
Once the T cells are exposed to the antigen by APCs, they can become Th1 cells (producing IFN-gamma), T regs or Th2 cells Th2 cells lead to the activation of B cells and the production of IgE antibodies

Question 20

Describe what happens in second exposure to the allergen.

Answer 20

In second exposure, the allergens are presented by APCs to memory Th2 cells, which then release IL-5, which causes eosinophil degranulation
Th2 cells also release IL-4 and IL-13, which stimulate production of IgE by plasma cells
The antigens crosslink the IgE on the surface of mast cells causing degranulation

Question 21

What percentage of blood leukocytes are eosinophils?

Answer 21

2-5%

Question 22

Describe the appearance of the nucleus of eosinophils.

Answer 22

Bilobed

Question 23

What receptors do mast cells have on their cell surface?

Answer 23

IgE receptors

Question 24

What mediators are released by mast cells?

Answer 24

Preformed: histamines, cytokines, toxic proteins

Newly synthesised: leukotrienes, prostaglandins

Question 25

What percentage of blood leukocytes are neutrophils?

Answer 25

55-60%

Question 26

What three processes cause airway narrowing in an acute asthma attack?

Answer 26

Vascular leakage leading to airways wall oedema
Mucus secretion fills up the lumen
Smooth muscle contraction around the bronch

Question 27

Describe the changes seen in a patient with chronic asthma.

Answer 27

The lumen of the airway is narrowed and the airway wall is grossly thickened
There will be cellular infiltration by Th2 lymphocytes and eosinophils
There will be smooth muscle hypertrophy, mucus plugging, epithelial shedding and subepithelial fibrosis

Question 28

State some important clinical features of asthma.

Answer 28

Chronic episodic wheeze 
Bronchial hyperresponsiveness  
Cough 
Mucus production  
Breathlessness  
Reduced and variable peak expiratory flow (PEF)

Question 29

What can allergic eczema lead to sensitisation of?

Answer 29

House dust mites – their proteins can get through dry, cracked skin

Question 30

What type of hypersensitivity is food allergy?

Answer 30

Type 1 hypersensitivity (IgE)

Question 31

What are the symptoms of a mild reaction to a food allergy?

Answer 31

Itchy lips and mouth
Angioedema
Urticaria

Question 32

What are the symptoms of a severe reaction to a food allergy?

Answer 32

Nausea
Abdominal pain
Diarrhoea
Anaphylaxis

Question 33

What is anaphylaxis?

Answer 33

Severe generalised allergic reaction

Question 34

What is anaphylaxis caused by?

Answer 34

Generalised degranulation of IgE sensitised mast cells

Question 35

State some symptoms of anaphylaxis.

Answer 35

Itchiness around mouth, pharynx and lips  
Swelling of the lips and throat  
Wheeze, chest tightness, dyspnoea 
Faintness, collapse  
Diarrhoea and vomiting

Question 36

How can you test for allergies?

Answer 36

Skin prick test

Question 37

What is the emergency treatment of anaphylaxis?

Answer 37

Adrenaline

Question 38

Describe the step-by-step treatment of asthma.

Answer 38

Step 1: short acting beta 2 agonist (e.g. salbutamol)
Step 2: low-moderate dose inhaled steroids (e.g. beclomethasone, budesonide, fluticasone)
Step 3: add long acting beta 2 agonist or a leukotriene receptorantagonist + high dose inhaled corticosteroids
Step 4: add courses of oral steroids

Question 39

What are the two types of immunotherapy that are used to develop tolerance in patients?

Answer 39

Subcutaneous immunotherapy (SCIT) 
Sublingual immunotherapy (SLIT)