Lecture 30 - Hypersensitivity, Allergy

Question 1

Type I hypersensitivity
1)
2)

Answer 1

1) Immediate hypersensitivity

2) IgE, mast cell, lipid mediators

Question 2

Type II hypersensitivity
1)
2)

Answer 2

1) Antibody-mediated hypersensitivity

2) IgM and IgG against cell-bound or ECM antigen

Question 3

Type III hypersensitivity
1)
2)

Answer 3

1) Immune complex hypersensitivity

2) IgM and IgG form immune complexes with antigen, complex deposition

Question 4

Type IV hypersensitivity
1)
2)

Answer 4

1) Delayed-type hypersensitivity

2) CD4+ mediated

Question 5

Atopic

Answer 5

1) Genetic predisposition to allergies

2) Enhanced tendency to produce IgE against environmental antigens

Question 6

Allergy
1)
2)

Answer 6

1) Type I hypersensitivity

2) Immune-mediated inflammatory response to otherwise harmless environmental antigens

Question 7

Traits of an atopic individual
1)
2)
3)

Answer 7

1) High levels of IgE (exact level varies with condition)
2) High levels of eosinophils
3) High levels of IL-4-secreting Th2

Question 8

Common features of allergens
1)
2) 
3)
4)
5)
6)

Answer 8

1) Inhaled antigens are highly-soluble proteins carried by small particles
2) Ingested antigens are highly resistant to degradation
3) Very stable
4) High solubility in body fluids
5) Introduced in very low doses
6) Induce Th2 response

Question 9

Most severe type of type I hypersensitivity

Answer 9

Anaphylaxis

Question 10

Phases of type I hypersensitivity
1)
2)

Answer 10

1) Sensitisation

2) Response

Question 11

Types of type I responses
1)
2)

Answer 11

1) Local (allergic rhinitis, bronchoconstriction, conjunctivitis)
2) Systemic (anaphylaxis, this is less common)

Question 12

Example of type I sensitisation and response 
1)
2)
3)
4)
5)
6)
7)

Answer 12

1) Enzyme Der p 1 from dust mites enters body
2) Der p 1 enzymatically degrades occludin in tight junctions between epithelial cells. Enters mucosa
3) Der p 1 is taken up by dendritic cells and presented in the nearest lymph node
4) Th2 is primed by DC presentation
5) Th2 induces B cell to differentiate to plasma cell, isotype switch to IgE (specific to der p 1)
6) Plasma cell travels to mucosa, releases IgE, which sensitise resident mast cells against der p 1 (FceR1)
7) Next time der p 1 is encountered, causes mast cell degranulation

Question 13

Which cytokines do Th2 secrete in response to sensitisation to allergen?

Answer 13

IL-4, IL-13

Question 14

Effects of mast cell stimulation in type I response
1)
2)
3)

Answer 14

1) Secretion of preformed mediators (histamine)
2) Synthesis and secretion of lipid inflammatory mediators (prostaglandin, leukotrienes)
3) Synthesis and secretion of cytokines (IL-3, IL-4, IL-5, IL-13)

Question 15

Effects of mast cell degranulation on GIT
1) 
2) 
3)
4)

Answer 15

1) Increased mucus, fluid secretion
2) Peristalsis
3) Vomiting (more severe)
4) Diarrhoea (more severe)

Question 16

Effects of mast cell degranulation on airways
1) 
2) 
3)
4)
5)

Answer 16

1) Decrease diameter
2) Increase mucus secretion
3) Wheezing
4) Coughing
5) Phlegm

Question 17

Effects of mast cell degranulation on blood vessels
1) 
2) 
3)
4)
5)
6)

Answer 17

1) Systemic effects, anaphylaxis
2) Increase blood flow
3) Increase permeability
4) Increase cells and proteins in tissue
5) Increase fluid in tissue
6) Increase lymph flow, effector response

Question 18

Immediate phase of type I response 
1)
2)
3)
4)
5)

Answer 18

1) Redness (flare)
2) Soft swelling - leakage of plasma from venules (wheal)
3) IgE mediated
4) Caused by release of preformed mediators (histamine)
5) Minutes after exposure to intradermal antigen

Question 19

Late phase of type I response
1)
2)
3)
4)
5)

Answer 19

1) Hard swelling
2) Accumulation of neutrophils, Th2, eosinophils
3) Involves oedema, smooth muscle contraction
4) Caused by induced mediators (chemokines, cytokines, leukotrienes)
5) Hours to days after exposure to intradermal antigen

Question 20

Immediate phase wheal and flare
1)
2)
3)

Answer 20

1) Wheal - localised swelling around site of challenge
2) Flare - Blood vessels around wheal dilate, become more permeable
3) Due to preformed mediators (histamine)

Question 21

Outcomes of type II response
1)
2)

Answer 21

1) Injury due to activation of effector mechanisms

2) Abnormal physiological response to antibody binding to antigen

Question 22

How can antibody binding to an allergen cause injury?
1)
2)
3)

Answer 22

1) C’ activation
2) Recruitment of inflammatory cells
3) Activation via Fc receptor

Question 23

Examples of diseases caused by abnormal physiological response in type II hypersensitivity
1)
2)

Answer 23

1) Grave’s disease

2) Myasthenia gravis

Question 24

Which type of hypersensitivity leads to haemolytic disease of a newborn?

Answer 24

Type II (due to preformed maternal IgG antibodies against newborn Rh+ blood cells)

Question 25

Haemolytic disease of a newborn
1)
2)
3)
4)

Answer 25

1) When a Rh+ baby is delivered from a Rh- mother
2) During delivery, baby’s RBCs enter mother’s bloodstream
3) Mother produces anti-Rh IgG - is now sensitised
4) If the mother has another child who is Rh+, maternal IgG cross the placenta, bind to foetus RBCs, cause C’ removal of them

Question 26

How is haemolytic disease of a newborn treated?
1)
2)

Answer 26

1) During delivery of the first child, administer anti-Rh antibodies to mother within 24 hours of delivery
2) These clear Rh+ RBCs from mother, so mother doesn’t produce anti-Rh antibodies

Question 27

What causes type III hypersensitivity?

Answer 27

Immune complexes formed from antibodies and antigens (self or foreign), that are either overproduced or improperly cleared

Question 28

What determines the pathology of type III hypersensitivities?

Answer 28

Where the immune complexes deposit.

EG: Cationic complexes can deposit on blood vessel walls and the kidney glomeruli

Question 29

Mechanism of type III hypersensitivity
1) 
2) 
3)
4)
5)
6)
7)

Answer 29

1) Immune complexes aren’t cleared (low Ab affinity, excess antigen, inefficient C’ activation)
2) Complexes deposited on blood vessel walls
3) Deposition eventually leads to C’ activation
4) Anaphylatoxins are generated (C3a, C4a, lead to neutrophil, mast cell degranulation)
5) Macrophage cytokine release stimulated
6) Immune complexes directly activate platelets, basophils, mast cells
7) Vasoactive amines lead to increased vascular permeability

Question 30

Immune complex-mediate damage
1) 
2) 
3)
4)

Answer 30

1) Immune complexes deposit on vascular wall, lead to disrupted blood flow, turbulence
2) Vasculitis
3) Glomerulitis (form deposition in kidney basement membrane)
4) Arthritis (deposition in joint synovium, vessels)

Question 31

What can elicit a type IV response?
1)
2)
3)

Answer 31

1) Microbial infection
2) Intradermal injection of protein antigens
3) Contact with chemicals (EG: absorbed through the skin)

Question 32

Stages of delayed-type hypersensitivity reaction
1) 
2) 
3)
4)

Answer 32

1) Antigen enters subcutaneous tissue, is taken up by resident DCs
2) DCs present antigen, tissue-resident Th1 detects antigen, proliferates
3) Cytokines released that act on vascular endothelium
4) Phagocytes, plasma recruited to region

Question 33

How long does a delayed type hypersensitivity response take?

Answer 33

12-72 hours, because Th1 need to be recruited

Question 34

Th1 cytokines in a delayed-type hypersensitivity reaction
1)
2)
3)
4)

Answer 34

1) Chemokines recruit macrophages to site of inflammation
2) IFNg - Induces expression of vascular adhesion molecules, macrophage activation
3) TNFa, LT - Induces expression of vascular adhesion molecules, local tissue destruction
4) IL-3/GM-CSF - stimulates macrophage production in bone marrow

Question 35

Skin-contact delayed type hypersensitivity reaction
1) 
2) 
3)
4)

Answer 35

1) Hapten crosses epithelium, is taken up by Langerhans cell
2) Langerhans cells present haptenated self peptides to resident Th1 (only happens if antigen has been contacted previously)
3) Th1 secrete IFNg, cytokines
4) Keratinocytes secrete chemokines, IL-1, TNFa

Question 36

Examples of pathogens that cause delayed-type hypersensitivity
1)
2)
3)
4)
5)
6)

Answer 36

1) Mycobacteria tuberculosis
2) M leprae
3) Leishmania spp
4) Schistosoma spp
5) Actinomycetes
6) Hepatitis B and C viruses

Question 37

Examples of antigens that cause delayed-type hypersensitivity 
1)
2)
3)
4)

Answer 37

1) Hair dyes
2) Nickel salts
3) Poison ivy (pentadecacatechol)
4) Thiomersol (in eye drops)

Question 38

Diagnostic test that makes use of delayed-type hypersensitivity

Answer 38

Mantoux test for TB

Question 39

Mantoux test

Answer 39

1) Tests for exposure to TB
2) Inject purified protein derivative (tuberculin) intradermally
3) If positive, after 48-72 hours, swelling at injection site, because of migration of lymphocytes

Question 40

How does TB cause type IV inflammation?
1)
2)
3)
4)
5)

Answer 40

1) TB is inhaled, multiplies in alveolar macrophages
2) Macrophage secretes IL-1, IL-12, TNFa. Presents TB antigen on MHCI, II
3) DC, macrophage, take up antigen, migrates to lymph node, presents antigen
4) Activated CD8+, Th1, migrate to lungs, secrete IFNg, further activate macrophages.
5) This process loops, as TB bacteria persist.