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

1. Organ specific autoimmune diseases: e.g. Myasthenia gravis (Anti-acetylcholine R Ab)
Glomerulonephritis (Anti-glomerular basement membrane Ab)
Pernicious anaemia (anti-parietal cells Ab)

2. 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 macrophage, CTLs and fibroblasts
Activated macrophages produce TNF-alpha, which is responsible for much of the tissue damage

Question 8

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

Answer 8

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

Question 9

What is atopy?

Answer 9

Atopy means genetic susceptibility to allergic reactions

Question 10

How common is atopy?

Answer 10

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

Question 11

List some genetic risk factors of atopy.

Answer 11

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 12

Among which age group is atopy most common?

Answer 12

Teens

Question 13

Describe the gender difference in asthma

Answer 13

Males – asthma in childhood is more common

Females – asthma in adulthood is more common

Question 14

What other environmental factors affect atopy?

Answer 14

Family size, infections, animals, diet

Question 15

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

Answer 15

Type 1 hypersensitivity

Question 16

What type of hypersensitivity is responsible for chronic urticaria?

Answer 16

Type 2 hypersensitivity

Question 17

What type of hypersensitivity is responsible for asthma, rhinitis and eczema?

Answer 17

Mixed- Type 1 and type 4 hypersensitivity

Question 18

Describe sensitisation in atopic airway disease.

Answer 18

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 19

Describe what happens in second exposure to the allergen.

Answer 19

In second exposure, the allergens are presented by APCs to memory Th2 cells, which then release IL-5, which causes eosinophil degranulation to release inflammatory mediators.

Inflammatory mediators are also released from Mast cells after binding of allergen to the IgE on mast cell surface + cross linking

Th2 cells also release IL-4 and IL-13, which stimulate MORE production of IgE by plasma cells too.

Question 20

What percentage of blood leukocytes are eosinophils?

Answer 20

2-5%

Question 21

Describe the appearance of the nucleus of eosinophils.

Answer 21

Bilobed

Question 22

What receptors do mast cells have on their cell surface?

Answer 22

IgE receptors

Question 23

What mediators are released by mast cells?

Answer 23

Preformed: histamines, cytokines, toxic proteins

Newly synthesised: leukotrienes, prostaglandins

Question 24

What percentage of blood leukocytes are neutrophils?

Answer 24

55-60%

Question 25

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

Answer 25

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

Question 26

Describe the changes seen in a patient with chronic asthma.

Answer 26

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 27

State some important clinical features of asthma.

Answer 27

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

Question 28

What can allergic eczema lead to sensitisation of?

Answer 28

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

Question 29

What type of hypersensitivity is food allergy?

Answer 29

Type 1 hypersensitivity (IgE)

Question 30

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

Answer 30

Itchy lips and mouth Angioedema Urticaria

Question 31

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

Answer 31

Nausea Abdominal pain Diarrhoea Anaphylaxis

Question 32

What is anaphylaxis?

Answer 32

Severe generalised allergic reaction

Question 33

What is anaphylaxis caused by?

Answer 33

Generalised degranulation of IgE sensitised mast cells

Question 34

State some symptoms of anaphylaxis.

Answer 34

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

Question 35

How can you test for allergies?

Answer 35

Skin prick test

Question 36

What is the emergency treatment of anaphylaxis?

Answer 36

Adrenaline

Question 37

Describe the step-by-step treatment of asthma.

Answer 37

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 38

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

Answer 38

``` Subcutaneous immunotherapy (SCIT) Sublingual immunotherapy (SLIT) ```