L24-25: Allergies

Question 1

Type I hypersensitivity reaction

Answer 1

Immediate hypersensitivity (IgE-mediated):
First exposure to allergen:
Th2 cell, previously driven down the Th2 pathway by recognition of Ag on a DC.
The same Th2 cell now recognises the same Ag in the context of MHC-II presented by B cell, releasing Th2 type cytokines driving class switching towards IgE.
IgE binds to its high affinity FcεR on mast cells.
Subsequent exposure to allergen:
Allergen-specific IgE bound to high affinity FcεR on mast cells cross-links IgE/FcεR, leading to activation of mast cell and release of inflammatory lipid mediators.
Production of IL-10 by TH2 inhibits the differentiation of T cells down the Th1 pathway

Question 2

Type II hypersensitivity reaction

Answer 2

Antibody-mediated (directed against cell surface or matrix Ags)

Question 3

Type III hypersensitivity reaction

Answer 3

Immune complex-mediated (directed against soluble Ag)

Question 4

Type IV hypersensitivity reaction

Answer 4

Delayed-type hypersensitivity (T cell mediated)

Question 5

FcεR constitutively expressed on

Answer 5

mast cells, basophils; induced by IL-5 in eosinophils as they are only recruited when needed

Question 6

Histamine mode of action

Answer 6

Histamine binding to H1 receptors cause vasodilation, plasma leakage, broncho-constriction of smooth muscle, intestinal hypermotility

Question 7

Mast cell released Lipid mediator mode of action

Answer 7

Exacerbate vascular leakage - cells leaking out of vasculature causing inflammation in tissues, prolonged smooth muscle constriction
Leukotrienes bind to different smooth muscle receptors than prostaglandins to cause long, rather than short term broncho-constriction

Question 8

Cytokines released by mast cells

Answer 8

IL-4: propagates Th2 response
TNF: activates endothelium promotes infiltration by leukocytes
IL-5: matures and activates eosinophils

Question 9

Immediate vs. late phase responses in allergy

Answer 9

Immediate reaction (seconds to minutes):
Due to preformed mediators such as histamine
Vascular permeability
Late-phase reaction (peaks at 8-12 hours):
Induced mediators, involve cell infiltrates and sustained oedema

Question 10

Eosinophils and allergic responses

Answer 10

Produce highly toxic granule-derived basic proteins and free radicals - responsible for tissue damage and remodelling
Produce chemical mediators leading to activation of epithelium.
IL-5 produced by Th2 leads to increased production of eosinophils. The production of CC chemokines further allows attraction and infiltration of eosinophils into tissues

Question 11

Role of basophils

Answer 11

Promote Th2 responses and IgE class switching
Basophils directly activated by protease Ag (allergens0 secrete IL-4 and IL-13
During naive CD4 T cell activation by APCs, IL-4 and 13 drive Th2 differentiation
CD40L on basophils binds to CD40 on allergen-stimulated B cells and along with Th2, further drives IgE class switching