Immunology: allergic disease and hypersensitivity

Question 1

What is the definition of a hypersensitivity reaction?

Answer 1

Immune response that results in bystander damage to the self

Question 2

What is type 1 hypersensitivity?

Answer 2

Immediate hypersensitivity i.e. allergy

Question 3

What is type 2 hypersensitivity?

Answer 3

Antibody mediated hypersensitivity

Direct cell killing

Question 4

What is type 3 hypersensitivity?

Answer 4

Immune complex mediated (i.e. antibody-antigen complex) hypersensitivity

Question 5

What is type 4 hypersensitivity?

Answer 5

Delayed type hypersensitivity i.e. T cell mediated

Question 6

What is the definition of allergy?

Answer 6

IgE-mediated antibody response to external antigen

Question 7

What are some of the environmental risk factors for developing allergy?

Answer 7

Westernised culture
Low exposure to bacteria - “hygiene hypothesis”
High antibiotic use

Question 8

What are the immune cells involved in the allergic response and what do they do?

Answer 8

B lymphocytes: recognise antigen and produce antigen-specific IgE antibody
T lymphocytes: provide help for B lymphocytes to make IgE antibody
Mast cells: release vasoactive substances

Question 9

What do B cells do in response to allergen?

Answer 9

Produce antigen specific IgE antibodies to clear antigen

Excess IgE antibodies bind to Fc receptors on mast cells

Question 10

What happens to mast cells after re-encounter with allergen?

Answer 10

Allergen binds to IgE-coated mast cells and causes degranulation, releasing vasoactive mediators, histamine, tryptase and increases transcription of leukotrienes and cytokines

Question 11

What is extrinsic asthma?

Answer 11

IgE mediated response to external allergen e.g. dust mite, pollen etc

Question 12

What is intrinsic asthma?

Answer 12

“Non-allergic” asthma i.e. genetic

Question 13

What effect does release of histamines from mast cells have on the lungs?

Answer 13

Bronchospasm
Inflammatory cell infiltration
Mucosal inflammation

Question 14

What is urticaria?

Answer 14

Hives

Question 15

What are some non-allergic i.e. non-IgE mediated causes of mast cell degranulation?

Answer 15

Urticaria in response to pressure or heat
Morphine and other opiates
Aspirin and non-steroidal anti-inflammatories
Thyroid disease
Idiopathic

Question 16

What is aspirin asthma?

Answer 16

Onset of wheeze 0.5-3 hours after ingestion of aspirin or other classical NSAIDS (particularly diclofenac, ibuprofen

Question 17

What is Samter’s triad?

Answer 17

Asthma, nasal polyps and salicylate sensitivity

This is on the severe end of the scale of asthma sensitivity

Question 18

What are some of the advantages of skin prick testing?

Answer 18

Cheap
Quick (15 minutes)
Unrivalled sensitivity for the majority of allergens, particularly aeroallergens

Question 19

What is an IgE specific/RAST test used for?

Answer 19

To measure amount of IgE in serum directed against specific allergen
Sensitivity and specificity about 70 to 75% compared with skin prick tests

Question 20

How can complement increase vascular permeability?

Answer 20

Fragments of complement proteins - anaphylotoxins - released after activation increase permeability of blood vessels
This is to increase traffic of cells to inflammation

Question 21

Give a clinical example of type 2 hypersensitivity.

Answer 21

Blood transfusion reactions

Question 22

What happens in blood transfusion/ABO reactions?

Answer 22

Anti-blood group antibodies bind to surface of circulating donor erythrocytes and form antigen-antibody complexes
This activates complement which stimulates phagocytosis

Question 23

What is the clinical presentation of Immediate Haemolytic Transfusion Reaction?

Answer 23

Overwhelming systemic inflammatory response:
Pyrexia and rigors
Tachycardia/tachypnoea 
Hypotension/dizziness
Headaches/chest or lumbar pain
May be fatal

Question 24

What are the two main forms of management of type 2 hypersensitivity reactions?

Answer 24

Immunosuppression

Plasmapheresis

Question 25

What is plasmapheresis?

Answer 25

Patient blood removed via cell separator
Cellular constituents replaced
Plasma replaced by plasma from someone else (FFP) or pooled immunoglobulin - approx. 50% plasma removed each time

Question 26

What is acute hypersensitivity pneumonitis?

Answer 26

Immune complexes deposited in the walls of alveoli and bronchioles in a type 3 hypersensitivity reaction e.g. bird fanciers lung

Question 27

Give an example of a systemic type 3 hypersensitivity reaction?

Answer 27

Systemic lupus erythematosus (SLE)

Antibodies produced against contents of cell nuclei

Question 28

What are some of the immune suppressant effects of corticosteroids?

Answer 28

Decreased release of proteolytic enzymes
Decreased traffic of phagocytes to inflamed tissue
Decreased phagocytosis
Decrease number of circulating lymphocytes
Inhibit antigen-induced Tcell proliferation
Decreased antibody production by plasma cells