HYPERSENSITIVITY

•Foreign Ag induces localized, specific, protective

inflammation

•Hypersensitivity is an undesirable, exaggerated

immune response (HMI or CMI) of detriment to the
host

•Hypersensitivity reactions can be divided into

sensitization and effector phases
 Types of Hypersensitivity

Immediate (Types I-III)

mediated by Ab or Ag-Ab
develops within min-hrs
Delayed (Type IV)
mediated by CMI (defence against
intracellular pathogens)
develops in days
Hypersensitivity Clinical
Reaction Mediator manifestation
I IgE Asthma, Urticaria,
II IgM, IgG Hemolytic anemia
III IgM, IgG Serum sickness
IV TDTH Contact dermatitis
Type I Hypersensitivity (Allergy)

Sensitization phase occurs when exposure to

an antigen (Allergen) induces IgE production

Common antigens associated with allergy
Proteins
foreign serum
vaccines
Plant pollens
Rye grass
Ragweed
Drugs
Penicillin
Sulfonamides
Foods
Nuts
Eggs
Seafood
Insect venom
Bee
Ant
Molds
Animal hair and dander
Isotype switching by IL-4
Target cells for IgE
1. Cells with high affinity Fc receptor

I. Mast cells (connective tissue around

blood vessels, skin, mucous
memb. of GIT & RT)
ii.Basophils (0.5-1% of WBC in
blood)

2. Cells with low affinity Fc receptor e.g.

B cells, MQ, eosinophils
•Degranulation: follows 2nd exposure to allergen
& cross-linkage of IgE, it leads to release of
phamacologically active mediators
•Mediators: act locally or systemically
•Biological effects of mediators:
Smooth muscle contraction
Vascular permeability
Vasodilatation
Act on eosinophils, MQ, neutrophils, etc.
(causing amplification of reaction &
clinical manifestation)
Types of mediators:

1o or preformed-stored (e.g. Histamine &

Chemotactic factors)

2o or newly synthesized (e.g. Cytokines-

IL-1, TNF etc)
 Principal mediators involved in allergy

Mediator Effects
Primary
Histamine Increased vascular permeability
smooth muscle contraction
Neutrophil chemotactic factor neutrophil chemotaxis
Serotonin Increased vascular permeability
smooth muscle contraction

Secondary
Platelet-activating factor (PAF) platelet aggregation & degranulation,
Cytokines (IL-1 & TNF) systemic anaphylaxis
Cytokines (IL-2, IL-3, IL-4, etc.) various effects
Genetic predisposition
Linked to MHC & non-MHC
component

e.g. one parent allergic 30% child is allergic

both " " 50% child is allergic
Factors involved in the production of
Allergy

• Genetic predisposition
• Nature & dose of Ag
• Sensitizing route (inhalation, ingestion)
• The extent of mediators released determine the
production of a localised or a systemic reaction
Localised Anaphylaxis

Local reaction, at site of allergen entry

The clinical manifestation (e.g. eczema, rhinitis,

asthma) is known as Atopy

Systemic Anaphylaxis

Shock-like state affecting both the cardiovascular

and respiratory systems, often fatal, onset within
minutes
Eczema, erythematous skin eruptions full of pus
Tests for Allergy
• The classical test for atopy is the Wheal &
Flare Reaction :
Injection of allergen into the skin

Degranulation of pre-sensitized,
IgE bearing local mast cell

Localized edema and erythema reactions

in allergic person in 30 min.
Advantages-inexpensive, allows screening of large
no. of allergens
2. Radioallergosorbent Test (RAST)
measures the allergen-specific IgE antibodies
present in the serum
 TREATMENT
Treatment of type I hypersensitivity is by:

3. Removal of house dust, pets etc. or avoidance

of the offending food.

2. Anti-histamine drugs that block the binding of

histamine to receptors and thus bringing about
symptomatic relief.

3. Drugs that block the degranulation of mast cells

such as adrenaline & cortisone.
4. Allergen immunotherapy
(Hyposensitization, desensitization)

is a kind of immunotherapy which involves the

injection of increasing doses of the allergen.
This is designed to stimulate the differentiation of
CD4+T cells to Th1 phenotype
This is thought to result in the induction of IgG
antibodies (instead of IgE) and
the induction of T suppressor cells.
It is believed that IgG neutralizes and eliminates
the allergen thus preventing the binding of the
allergen to mast cells.

T suppressor cells may also suppress the IgE

response.