Lecture 25 - Allergy and Hypersensitivity

What is Type I hypersensitivity?

Also called immediate hypersensitivity. It is mediated by IgE and mast cells.
Examples: Hay fever, asthma, anaphylaxis.

What is Type II hypersensitivity?

Antibody-mediated cytotoxicity, involving IgG or IgM attacking cells.
Example: Haemolytic disease of the newborn (Rh incompatibility).

What is Type III hypersensitivity?

Immune complex-mediated. Antigen-antibody complexes trigger inflammation.
Example: Serum sickness, some types of vasculitis.

What is Type IV hypersensitivity?

Delayed-type hypersensitivity, mediated by T cells (not antibodies).
Examples: Tuberculin (Mantoux) test, contact dermatitis (e.g. poison ivy).

What mediates Type I hypersensitivity?

IgE antibodies and mast cells. It occurs within seconds to minutes of exposure.

What are common allergens in Type I reactions?

Respiratory: pollen, dust mites, pet dander
Skin: nickel, hives
Food: peanuts, shellfish
Insects: bee or wasp stings
Drugs: penicillin

What is anaphylaxis?

A severe, life-threatening systemic allergic reaction caused by widespread mast cell degranulation.

How does IgE trigger allergy in Type I reactions?

First exposure: B cells switch to produce IgE
IgE binds Fcε receptors on mast cells
Re-exposure: allergen cross-links IgE → mast cells degranulate
Histamine, prostaglandins, leukotrienes, and cytokines are released

What symptoms are caused by mast cell degranulation?

Sneezing, swelling, itching, wheezing, rash, and in severe cases, shock.

What is an example of a Type II hypersensitivity?

Rhesus (Rh) incompatibility in newborns – haemolytic disease of the fetus/newborn.

How does Rh haemolytic disease occur?

Rh− mother exposed to Rh+ fetal blood → makes IgG antibodies
In later pregnancy, IgG crosses placenta and destroys fetal RBCs

How is Rh disease prevented?

RhoGam injection (anti-Rh IgG) during pregnancy to destroy fetal Rh+ RBCs before mother reacts.

What is an example of Type IV hypersensitivity?

The Mantoux test for tuberculosis.

How does the Mantoux test work?

Inject PPD (TB antigen) into skin
If previously exposed, memory T cells activate
Inflammation peaks after 48–72 hours

What is contact dermatitis?

A Type IV hypersensitivity caused by skin exposure to allergens like poison ivy or nickel.

What is allergic desensitisation (immunotherapy)?

Gradual exposure to allergen to reduce IgE response and increase IgG production.

How does desensitisation therapy work?

IgG acts as a "decoy," binding the allergen before IgE
Prevents mast cell activation
Works in about 50% of patients

What are monoclonal antibodies (mAbs)?

Lab-made antibodies that bind to a single, specific epitope.

How are monoclonal antibodies made?

Mouse is immunised with antigen
Spleen B cells are fused with myeloma cells
Resulting hybridomas make identical antibodies

What are examples of monoclonal antibodies used in medicine?

Infliximab: Blocks TNF-α – for RA, Crohn’s
Pembrolizumab: Blocks PD-1 – for cancer
(Note: all end in "-mab")

What are pros of mAbs?

High specificity, long half-life, can be humanised

What are cons of mAbs?

Expensive, may cause side eff