Mechanisms of Hypersensitivity

Question 1

What is hypersensitivity?

Answer 1

An inappropriate immune response to non-infectious antigens that results in tissue damage and disease

Question 2

What are the four types of hypersensitivity?

Answer 2

• Type 1 = Immediate Hypersensitivity
• Type 2 = Cytotoxic Hypersensitivity (Antibody mediated diseases)
• Type 3 = Serum Sickness and Arthus reaction (Immune complex mediated diseases)
• Type 4 = Delayed-type hypersensitivity

Question 3

Describe type I hypersensitivity

Answer 3

1. Results from being exposed to allergens in the environment
2. Th2 activation and IL-4 secreting Tfh (T-follicular helper cells) which will stimulate the production of IgE antibodies
3. IgE will attach to the FcεRI on mast cells
4. Subsequent exposure of antigen leads to cross-linking of the bound IgE by the antigen
5. Activation of mast cells and degranulation of contents = inflammation

Question 4

What are examples of type I hypersensitivity reactions?

Answer 4

• Eczema
• Asthma
• Allergic rhinitis
• Anaphylaxis
  
  • Far more exaggerated response to an allergen, increase in oedematous tissue, airway restriction, tongue swelling, low blood pressure

Question 5

How will you induce an immediate hypersensitivity reaction?

Answer 5

1. We can induce an immediate hypersensitivity reaction by injecting/ or scratching an allergen into the skin
2. If we have mast cells that are carrying a specific IgE to that allergen, then the IgE will be cross-linked and the mast cells will become activated
3. Mast cells will release inflammatory mediators causing
4. Leakage of plasma fluid and protein into tissues = bump on surface of the skin (wheal)
5. Vasodilation = results in a flare response
   
   • We get a typical weal and flare response

Question 6

Describe Type 2 Hypersensitivity (Cytotoxic Hypersensitivity)

Answer 6

• This is an immune response generated by altered components of the human cells
  
  • IgM and IgG antibodies will be produced against cell surface or extracellular matrix antigens
    
    • For example penicillin can attach modify proteins on RBC cell surface creating foreign epitopes recognised by the immune system
    • They will create an IgG response against that allergen
    • This will bind and activate macrophages through FcyR binding and complement activation

Question 7

What are some examples of cytotoxic hypersensitivity?

Answer 7

• Penicillin
  
  • Myasthenia Gravis
  • Graves’ disease
    
    • For these an IgG antibodies will be directed at cell surface receptors
      
      • These antibodies will disrupt the normal functions of the receptor through uncontrollable activation or blocking of receptor function
• Haemolytic Disease of Newborn

Question 8

What is myasthenia gravis?

Answer 8

• Autoimmune disorder = Antibodies can block and destroy the nAchR on the post-synaptic junction causing nerve transmission to be blocked and paralysis
• Normally Ach will be released which will stimulate nAchR at neuromuscular junction causing muscle contraction and neuromuscular junction

Question 9

What is Graves Disease/Thyrotoxicosis?

Answer 9

Normally the pituitary will release TSH which will activate the thyroid to produce thyroxine which will then cause a negative feedback on thyroid gland

However, autoantibodies can be generated against the TSH receptor which leads to uncontrollable activation and unregulated production of thyroid hormones

Question 10

Describe Haemolytic Disease of the Newborn

Answer 10

• During pregnancy if the mother is RhD -ve and the foetus is RhD +ve
• The embryonic chorion will normally separate the mothers and the foetuses blood supply
• During delivery there will be disruption of the embryonic chorion and release of foetal RBCs in the maternal circulation
• The mother will make an IR against the RhD +ve antigens
• If the mother is pregnant with a second child, the antibodies which were produced against the antigens from the RhD +ve foetus during delivery can cross the placenta
  
  • These can attack the developing foetuses’ RBCs and cause haemolytic anaemia and death
    *

Question 11

Describe type 3 hypersensitivity (serum sickness + arthus reaction)

Answer 11

This occurs when there is a presence of a soluble antigen