Hypersensitivity

Question 1

Summarise the 4 types of hypersensitivity.

Answer 1

I: IgE mediated hypersensitivity
II: IgM and IgG mediated hypersensitivity
III: immune complex mediated hypersensitivity
IV: T-cell mediated hypersensitivity

Question 2

Explain how type I hypersensitivity leads to mast cell degranulation.

Answer 2

• first exposure to allergen activates Th2 T-cells, stimulating IgE production
• IgE uses Fc receptor to bind to FC€R1 on mast cells, sensitising mast cells
• when mast cell that is sensitised by IgE is exposed to allergen again, allergens bind to antigen binding site on multiple IgE, causing Fc region on bound IgE to crosslink with each other
• this triggers signalling cascades that activate and degranulate mast cells

Question 3

Identify the molecules involved in early phase reaction of type I hypersensitivity.

Answer 3

• molecules are the contents of granules after mast cell degranulation
• histamine: vasodilation, increase in vascular permeability, intestinal and bronchial smooth muscle contraction
• proteases: cause damage to local tissues
• lipid mediator prostaglandin: vasodilation, chemotaxis of neutrophils to the site
• lipid mediator leukotrienes: bind and cause prolonged smooth muscle contraction
• lipid mediator platelet activating factors: bind to smooth muscle cells and cause bronchoconstriction
• cytokines: IL-4 and IL-13 for Th2 response, IL-5 activates eosinophils, TNF-alpha causes leukocyte adhesion to endothelial cells

Question 4

What are the clinical features associated with early phase type I hypersensitivity?

Answer 4

• increased GI fluid secretion and peristalsis causes expulsion of GI contents via diarrhoea and vomiting
• bronchoconstriction of airways and increased mucous secretion leads to asthma
• increased blood flow and permeability can lead to lymphoedema, circulatory collapse and systemic anaphylaxis
• allergic rhinitis
• acute urticaria

Question 5

What is the late phase reaction in type I hypersensitivity?

Answer 5

Release of inflammatory mediators by mast cells leads to recruitment of leukocytes and inflammation

Question 6

What are the treatments for type I hypersensitivity?

Answer 6

• anaphylaxis: epinephrine
• bronchial asthma: corticosteroids, leukotrienes antagonists, phosphodiesterase inhibitors
• general: antihistamines, anti- IgE antibodies, cromolyn to prevent mast cell degranulation

Question 7

Describe the process of type II hypersensitivity.

Answer 7

• damage to tissues mediated by IgG and IgM
• anti-tissue antibody deposits into tissues, resulting in antibody responses
• complement system activation causes inflammation at the site
• opsonization and phagocytosis for host cells

Question 8

What is myasthenia gravis?

Answer 8

• a type II hypersensitivity reaction
• antibodies attack nicotinic acetylcholine receptors at NMJ
• leads to reduced neurotransmission and muscle weakness
• characteristic ptosis (eyelid drooping)

Question 9

What is Graves disease?

Answer 9

• a type II hypersensitivity reaction
• production of antibody against TSH receptor
• stimulation of receptor without hormone
• leads to hyperthyroidism

Question 10

What is Haemolytic disease of the Newborn?

Answer 10

• type II hypersensitivity reaction
• antibodies attack Rh antigens in newborn when the mother lacks Rh in her own RBCs

Question 11

Describe the process of type III hypersensitivity.

Answer 11

• damage to blood vessels (vasculitis) mediated by immune complexes
• immune complexes deposit in blood vessels, resulting in inflammation
• antibody responses include complement system activation, opsonization and phagocytosis of the host cells

Question 12

What is systemic lupus erythematosus?

Answer 12

• type III hypersensitivity response
• antibodies attack self-antigens on cells and form immune complexes
• immune complexes can deposit at different areas, causing widespread inflammation and erythema

Question 13

What is Arthus disease?

Answer 13

• type III hypersensitivity response
• local antigen bound to IgM or IgG causes immune complex formation and agglutination
• this causes local vasculitis, increased fluid and protein release and blood vessel occlusion (bc of agglutination)

Question 14

What are the treatments for type II and type III hypersensitivity?

Answer 14

• corticosteroids to reduce inflammation
• anti CD40 and anti CD40-L to inhibit antibody production
• anti-CD20 to deplete B-cells
• plasmapheresis to reduce levels of antibodies or immune complexes

Question 15

Where is type IV hypersensitivity seen?

Answer 15

• autoimmunity reactions
• environmental antigens binding to self proteins, making them appear foreign

Question 16

What is the mechanism of type IV hypersensitivity?

Answer 16

• CD4 Th1 releases cytokines
• cytokines cause inflammation and tissue damage by activating M1 macrophages, IgE production + mast cell degranulation, and Th2 eosinophil activation
• CD8 Tc-cells directly kill target host cells, causing tissue damage

Question 17

What is contact dermatitis?

Answer 17

• type IV hypersensitivity reaction
• contact sensitising agent penetrates the skin and binds to self proteins
• Langerhans cells (epithelial DCs) phagocytose agent and present antigens to Th1 cells
• Th1 cells release IFN-gamma to activate macrophages, attacking self-proteins and causing inflammation

Question 18

What are the treatments for type IV hypersensitivity reaction?

Answer 18

• corticosteroids to reduce inflammation
• anti-B7, or antagonists to cytokine receptors to inhibit T-cell function