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• Sensitization phase
Mechanism of type I hypersensitivity • Allergen

• stimulates B lymphocyte with

• Three phases: production of IgE
(requires the assistance
of Th2 cell
– Sensitization phase
– Activation phase
– Effector phase • binds firmly by its Fc portion to
Fc receptor of mast cells &
Basophlis

• Arming of mast cell

• Activation phase • Effector phase

• Reexposure to the same
antigen Triggering of mast cell

• Multivalent antigen binds to

more than one IgE Mast cell Newly
& cross linking of adjacent degranulation synthesis
IgE

• It activates signals Release of

transduction pathways and primary Release of
leads to triggering of mast mediators secondary
cell mediators

Important mediator-
Primary mediators Secondary mediators Action of mediators
(Preformed mediators) (Newly synthesized)

¤Histamin, ¤ slow-reacting substance of • Vasodilatation

¤ serotonin, anaphylaxis (SRS-A), • Increased capillary permeability
¤ prostaglandin
• Bronchial smooth muscle contraction
¤ Eosinophil chemotactic factor of
• Increase mucous secretion
anaphylaxis (ECF) ¤ Bradikinine
• platelet activation
¤ Neutrophlil chemotactic factor of ¤ Platelet activating factor
• Acts as anticoagulant
anaphylaxis (ECF) • Cytokines-IL-4, IL-5, IL-13, IL-9

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• Systemic or anaphylactic reactions usually follows-

– Injection which may lead to shock &
– Is sometimes fatal
– Examples are-Penicilin, foods like peanut and shellfish, Bee
TYPE I venom
HYPERSENSITIVITY
• Local reactions depends upon the portal of entry of the
allergen-
Examples are-
SYSTEMIC LOCAL – Skin allergy
– Allergic rhinitis & conjuntivitis
ANAPHYLAXIS ATOPY
– Bronchial asthma

• Prevention of Type I hypersensitivity Anaphylactoid Reaction

• Avoidance contact with known allergens • A reaction clinically & pathologically identical to anaphylaxis can
occur without the participation of an IgE antibody & corresponding
• Immunotherapy: allergen. This phenomenon is called anaphylactoid reaction.
- Hyposensitization- Long term repeated subcutaneous
injection of allergen some time reduce the severity of Type • Causes of anaphylactoid reaction:
I hypersensitivity or even eliminate completely. • Exercise
• Emotions
• Overheating
-Humanized monoclonal anti-IgE • Exessive cold
• Adminstration γ globulin
• Radiographic iodinated contrast media
• Polymixin B
• Drugs - NSAID
Opiates

Atopy SERUM SICKNESS

Atopic disorder such as hay fever, asthma, eczema and
urticaria, are immediate- hypersensitivity reactions with
both an environmental trigger and a strong familial
predisposition .
Atopy is associated with elevated IgE level and target
tissue often contain large numbers of Th-2 cell, which
play a major role in the pathogenesis of atopic reaction.
• Acute serum sickness is a systemic immune complex
mediated disease due to presence of immune complexes
deposited in many areas of the body.
• Eg: penicillin, diptheria antitoxin,ATS
• Results from deposition of soluble immune complexes
formed in antigen excess.
Three phases:
Formation of Ag-Ab complexes with slight Ag excess.

Deposition of Immune complex in various tissues.

Mutation in the gene encoding the alpha chain of IL4
receptor strongly predispose to atopy. These mutation
enhance the effectiveness of IL4,resulting in an increase Initiation of inflammatory reaction in dispersed sites
throught out the body.
amount of IgE by synthesis by B cell.

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• ARTHUS REACTION

Symptoms are • When antigen is injected intrdermally in a sensitized person it

diffuses towards blood vessels which contain circulating
antibody.
• Fever
• Urticaria In a condition of excess Ab insoluble immune complexes are
formed & deposit in or near vessel wall.
• Arthalgia
Activation of classical pathway of complement.
• Lymphadenopathy
• Spenomegaly Chemotactic complement factors attracts neutrophil which
together with platelet causes vascular occlusion.

End result is the rupture of vessel wall &

hamorrhage accompanied by necrosis.

• EXAMPLE- Farmer’s lung.

Type IV
or
Cell mediated hypersensitivity
or • DTH is mediated by - Macrophage &
Delayed type Hypersensitivity - CD4 cells - particularly by Th 1 subsets.
Type IV is called Delayed type Hypersensitivity because the - CD8 cell-in some casescells occasionally
response is delayed. It starts hours or days after primary
contact with antigen and often lasts for days. • EXAMPLES:
Tuberculin test/Tuberculosis
• The hallmark of Type IV hypersensitivity- Lepromin reaction in tuberculoid leprosy.
– delay of onset Contact dermatitis
– recruitment of macrophage Granulomatous inflammation
– Erythema Multiforme

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Initial sensitization phase:
• After primary contact with antigen macrophage ingest the
antigen and IL 12 is produced. IL12 induces naive Th0 cell to
becomeTH1 cells.
• TH cells are activated & clonally expanded and memory cells to
the Ag are formed.
• IL-2 leads to proliferation of Th1 cell and activation of
cytotoxic T cell.
• TNF activates endothelial cells.
• These leads to increased vascular permeability and
the recruitment and activation of CD4 Th1 cells,
macrophages and cytotoxic T cells.
• IFN Ύ activates macrophages. The net effect of the
activation of MQ is to release of lytic enzymes
that cause localized tissue damage.
• Tissue injury occurs by T cell derived cytokines and
activated macrophages.
TYPE V HYPERSENSITIVITY
(STIMULATORY HYPERSENSITIVITY)
EXAMPLE: Autoimmune thyroiditis
(GRAVE’S DISEASE)
The production of thyroid hormones is regulated by When
thyroid stimulating hormone (TSH) of pitutary origin, which
binds to thyroid cell receptor stimulate the thyroid cell to
produce thyroid hormones.
Effector phase:
– Subsequent exposure to the same Ag CD4TH 1 secrete a variety of
cytokines like IL2,TNF,INFɣ that recruit & activate macrophage &
other nonspecific inflammatory cells.
• Granuloma formation-
• It results from persistence of microorganisms
within the macrophage, which the cell is
unable to destroy.
• In case of certain persistent or undegradable
antigen,e.g-Mycobacterium Tuberculosis
colonizing lungs or other tissue, the initial
perivascular lymphocytic infiltrate become
replaced by macrophage over a period of 14
to 21 days.
-In graves disease Autoantibody
directed against TSH receptor (LATS)
is produced.
-Binding of these autoantibody to the
receptor produces an effect similar
to TSH,resulting in production of
thyroid hormones.
-Unlike TSH, autoantibody are not
regulated and consequently they
overstimulate the thyroid and excess
production and secretion if thyroid
hormone occur, which is responsible
for GRAVE’S DISEASE