Hypersensitivity

The airways are also prone to being affected by hypersensitivity reactions – these are abnormal immune responses to normal stimuli. These are categorised into 4 different types.

Type 1

This is a rapid allergic reaction due to pre-formed IgE antibody to an exposed antigen.

– It eventually leads to a large increase in histamine which can lead to anaphylactic shock.

Histamine is stored in mast cells and is released by calcium-dependent exocytosis:

– IgE binds IgE receptor –> increases intracellular IP3 –> increases Calcium

– Intracellular cAMP is an antagonist and works to block release of histamine

Histamine binds to 2 main types of Histamine receptors:

H₁ (G_q coupled) –> increases IP3 + DAG

– Causes smooth muscle contraction in ilium, uterus and bronchi

– Causes blood vessel dilation by activating nitric oxide synthase

– Causes itching

H₂ (G_s coupled) –> Increase in cAMP + PKA

– Increases gastric acid secretion + heart rate

Type 2

This results from antibodies IgM/IgG binding to cell/tissue antigens

– It causes clearance of the antigen by tissue macrophages in the spleen, or by complement lysis

e.g. Blood groups – RBCs have a H antigen which can be modified in two ways (A/B antigen)

– We have pre-existing antibody for the other antigen.

O – contains unmodified H antigen –> produces anti-A and anti-B antigens

A – has H antigen + A modification –> produces anti-B antibodies

B – has H antigen + B modification –> produces anti-A antibodies

AB – has H antigen + both modifications –> no antibodies 

If the wrong blood group is given, this results in an antibody mediated hypersensitivity reaction. 

Type 4

This is delayed type hypersensitivity mediated by specific CD4 Th1 cells.

– Takes days to develop and needs 1000x more antigen

– When the antigen is re-encountered, Th1 cells recruit macrophages and inflammatory cytokines to cause inflammation.