Hypersensitivity reactions

Occur on 2nd or subsequent exposure to an antigen
Abnormal reactions involving different immune mechanisms
4 types

Type 1 (immediate)
IgE mediated
IgE synthesised by B lymphocytes on 1
st exposure and binds to mast cells (numerous in bronci, gut, capillaries)
On 2
nd exposure mast cells degranulate releasing vasoactive substances (histamine, serotonin, heparin, leukotrienes, PLT activating factor)

Type 2 (cytotoxic)
IgE and M with complement cause cytotoxic cell lysis
Haemolysis, thrombocytopenia
Drug induced

Type 3 (immune complex)
Antibody and antigen react producing an immune complex which deposits in small vessels (lungs, glomeruli, joints)
Underlies many autoimmune diseases

Type 4 (delayed)
T-cells and macrophages attack foreign material
Occurs without complement or antibodies
Contact dermatitis
Granuloma formation

Clinically indistinguishable from anaphylactic reactions
Direct release of vasoactive substances from mast cells
Not mediated via an antigen-antibody response
Dose related (why give drugs slowly)

Investigation of hypersensitivity reactions

An enzyme released from degranulating mast cells which activates complement cascade
Investigate reactions by serum for tryptase immediately, 1h and 6-24h
Higher values more likely to be IgE mediated

Radioallergosorbent tests (RAST) now superseded by CAP (antigen coated capsule exposed to patients serum)
Penicillin, sux and latex only – low sensitivity so need skin prick tests too

Skin prick
(or intradermal) testing
4-6/52 post event to allow regeneration IgE
Drop applied to forearm and lancet stabbed through it to break skin
-ve control with saline
+ve control with histamine
Undiluted drug – if reaction then repeated with 1 in 10 dilution