Hypersensitivity reactions (asthma and allergy)

Question 1

How is hypersensitivity classified

Answer 1

• Type 1: Immediate hypersensitivity
• Type 2: Cytotoxic hypersensitivity
• Type 3: Serum sickness and Arthus reaction
• Type 4: Delayed-type hypersensitivity, contact dermatitis

Question 2

Describe how type 1: Allergy mechanism works

Answer 2

• Mediated by IgE
• There is an interaction between mast cells, IgE and the allergens
• causes degranulation and releases cytokines for an allergic response
• Consequences are allergic rhinitis, Asthma and anaphylaxis

Question 3

Describe what happens with systemic anaphylaxis

Answer 3

• Severe localised oedema
• Vey progressive reaction
• Occlusion of airways and causes asphyxia
• Treated with adrenaline (Epi-pen)

Question 4

Describe how type 2 hypersensitivity mechanism works

Answer 4

• Mediated by IgG (anti-drug antibodies)
• Drug binds red blood cells or platelets and antibodies bind to the drug
• Antibody-bound cells are cleared by macrophages and form complements
• Leads to inflammation and disease

Question 5

Explain how graves disease is an example of Type 2 hypersensitivity

Answer 5

• IgG antibodies are made against the TSH receptor
• IgG blocks receptor binding which results in the inhibition of the negative feedback cycle
• Excess thyroid hormone is produced

Question 6

Give some other examples of type 2 hypersensitivity

Answer 6

• Myasthenia gravis
• Newborn haemolytic disease

Question 7

Describe how type 3 hypersensitivity mechanism works

Answer 7

• Mediated by IgG
• A soluble antigen comes in contact with antibodies
• IgG and antigen form immune complexes
• Immune complexes cleared by phagocytes

Question 8

Describe how serum sickness is type 3

Answer 8

• 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.
• Iissue damage is caused
  by complement activation
  and the subsequent
  inflammatory responses

Question 9

Describe how farmers lungs is an example of type 3

Answer 9

• Hay or grain dust is inhaled into farmers lungs
• Causes a type 3 hypersensitivity reaction
• Inflamed lungs

Question 10

Describe how type 4 hypersensitivity mechanism works

Answer 10

• T-cell mediated response to antigens
• T cell gets activated and activates macrophages which release chemokine, cytokine and cytotoxins

Question 11

Explain the time-delayed nature of type 4 hypersensitivity

Answer 11

• Takes time for T cell activation to happen and differentiate into effector cells to carry out the response

Question 12

List some examples of type 4 hyper sensitivity reactions

Answer 12

• Mantoux test
• Tuberculoid leprosy
• Contact dermatitis
• Poison ivy

Question 13

Describe the characteristic of the IgG antibody

Answer 13

• First line of defence against worms
• Binds FcεR1 receptor on mast cells
• Pre-arms mast cells to react when in the
  presence of antigen

Question 14

Describe the allergen-specific IgE production model

Answer 14

• There is initial exposure to pollen
• IL-4 drives B cells to produce IgE in response to pollen antigens
• Pollen specific IgE binds to mast cells

Question 15

What factors determine allergen sensitivity

Answer 15

• Nature of allergen
• Dosage of Allergen
• Timing
• Location of priming
• Role of pro-allergic dendritic cells and cytokines
• genetic predisposition to allergy

Question 16

What are some characteristics of common allergens

Answer 16

• Examples include: dust mites, pollens and cockroaches
• Named after the source organism and the order of discovery
• Allergens have common functionalities such as proteases
• Normally received in small doses
• High-dose exposure may lead to tolerance

Question 17

What are filaggrin and atopic dermatitis

Answer 17

• Filaggrin links skin integrity
  and allergy
• When it is defective atopic dermatitis is greater
• This is due to the access for allergens

Question 18

What makes dendritic cell pro-allergic

Answer 18

Not Known but One Candidate Protein is TSLP This may switch DC to a ‘pro- allergic’ state

Question 19

What happens to mast cells when activated by allergens

Answer 19

• Resting mast cell contains granules containing histamine and other inflammatory mediators
• Multivalent antigen cross-links bound IgE antibody causes release of granule contents

Question 20

What causes early and late phase allergic response

Answer 20

• Early phase is immediate and mediated by mast cells
• The late phase is delayed and is mediated by T cells

Question 21

What effector mediators are produced by mast cells in the early phase

Answer 21

• Histamine - Increases vascular permeability and cause smooth muscle contraction
• Leukotrienes - increase vascular permeability, smooth muscle contraction and stimulate mucus secretion
• Prostaglandins - chemoattractant for T cells, eosinophils and basophils

Question 22

What effector mediators are produced by mast cells in the late phase

Answer 22

Cytokines:

• IL-4 and IL-13 - promotes Th2 and IgE
• TNF-a - promotes tissue inflammation

Question 23

what are the effects of mast cell activation the GI tract

Answer 23

• Increased fluid secretion
• Increased peristalsis
• Causes expulsion of GI tract contents

Question 24

What are the effects of mast cell activation on the airways

Answer 24

• Decreased diameter
• Increased mucus secretion
• Congestion and blockage of airways
• Swelling and mucus secretion in nasal passages

Question 25

What are the effects of mast cell activation on blood vessels

Answer 25

- Increased blood flow - Increased permeability - Increased fluid in tissues causing increased flow of lymph to lymph nodes - Increased cells and protein in tissue - Increased effector response in tissues

Question 26

what are the effector function of eosinophils

Answer 26

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

Question 27

Describe the late phase of the IgE mediated allergic response

Answer 27

- Late-phase reaction is dependent on allergen dose - Continued synthesis and release of inflammatory mediators - Chronic allergic inflammation caused by Th2 cells i.e. a type IV hypersensitivity reaction

Question 28

what is Asthma

Answer 28

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

Question 29

List some characteristics of asthma

Answer 29

- 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 30

Describe the acute response to allergic asthma

Answer 30

- 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 31

Describe the chronic response to allergic asthma

Answer 31

- 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 32

how can we treat asthma

Answer 32

- 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)