Hypersensitivity reactions

Question 1

What is Type 1 hypersensitivity reaction?

Answer 1

An ‘allergic’ reaction that immediately follows contact with an antigen that would not normally cause a marked immune response

Question 2

Describe the mechanism of Type 1 hypersensitivity reaction?

Answer 2

• Mast cells bind IgE via their Fc receptors
• On encountering the antigen, the IgE becomes crosslinked
• This leads to degranulation and release of mediators (e.g. histamine, serotonin, platelet activating factors, eosinophil chemotactic factors)
• Histamine acts as a mediator of negative feedback inhibiting mast cell degranulation

Question 3

Give examples of Type1 hypersensitivity reactions

Answer 3

• Seasonal allergic conjunctivitis
• Perennial allergic conjunctivitis

Question 4

What is Type 2 hypersensitivity reaction?

Answer 4

• Antibody dependent cytotoxicity hypersensitivity
• Arises from antibodies directed against antigens expressed on an individuals own cells (can be extrinsic antigens e.g. drugs or intrinsic antigens)

Question 5

Describe the possible mechanisms of Type II hypersensitivity

Answer 5

1. Self antigen recognised by auto-antibody (IgE/igM)
   - Macrophage/NK cell binds to Fc tail of antibody
2. Self antigen recognised by auto-antibody (IgE/igM)
   - Complement binds to Fc tail of antibody
   - Activation of complement cascade to membrane attack complex
   - Binding of neutrophils to C3b component of complement

Question 6

Give examples of Type II hypersensitivity reactions

Answer 6

• Incompatabile blood transfusions
• Hyper acute graft rejections
• Rhesus incompatibility of the newborn
• Myasthenia gravis

Question 7

What is Type III hypersensitivity reaction?

Answer 7

Immune complexes are deposited in the tissue

Question 8

Describe the mechanism of Type III hypersensitivity reactions

Answer 8

• Immune complexes are deposited in tissue
• Complement is activated and polymorphs are attracted to the site of deposition
• This causes acute inflammation

Mechanism is dependent on:
1. Turbulent blood flow, allowing deposition of immune complexes e.g. Kidney
2. Increased vascular permeability due to histamine release
3. Specific antigen-antibody complexes

Question 9

Give examples of Type III hypersensitivity reactions

Answer 9

• Arthus reaction
• RA
• SLE
• Persistent infections e.g. viral hepatitis

Question 10

What is the Arthus reaction?

Answer 10

Occurs after injection of an antigen intradermally in people who have previously been exposed (e.g. immunisation) and therefore have high antibody levels.

The antigen-antibody complex is deposited causing an acute inflammatory reaction lasting 4-10 hours.

Question 11

What is a Type IV hypersensitivity reaction?

Answer 11

T Cell mediated hypersensitivity

Question 12

Describe the mechanism of T cell mediated hypersensitivity

Answer 12

• Antigen sensitised T cells release cytokines following a second contact with the same antigen
• The cytokines induce inflammatory reactions and attract and activate macrophages to release mediators

Question 13

Give examples of Type IV hypersensitivity reactions

Answer 13

• Contact hypersensitivity by an epidermal reaction via Langerhans’ cells (peaks at 48 hours)
• Tuberculin type hypersensitivity caused by subdermal injection of tuberculin producing a reaction in the dermis that peaks at 48-72 hours (mantoux test)
• Cell mediated hypersensitivity results in a granulomatous reaction and is usually caused by persistent antigen in macrophages (TB) - reaction peaks at approx 4 weeks
• Giant papillary conjunctivitis, vernal keratoconjuctivitis, atopic keratoconjuctivitis are all part Type 1 and type IV reactions