HYPERSENSITIVITY

A damage to host mediated by

preexisting immunity to self or
foreign antigen

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 Impact
Impact of
of allergic
allergic diseases
diseases
allergic condition estimated number
affected (million)
Allergic rhinitis 19.6
Chronic sinusitis 32.5
Contact dermatitis & eczema 5.8
Skin rashes 12
Asthma 9-12
Anaphylaxis 1-2

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 Types
Types of
of hypersensitivity
hypersensitivity
reactions
reactions

Type
Type I:I: anaphylactic
anaphylactic or
or immediate
immediate
Type
Type II:
II: cytotoxic
cytotoxic
Type
Type III:
III: Immune
Immune complex
complex
Type
Type IV:
IV: cell
cell mediated
mediated or
or delayed
delayed

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Type-I
Type-I hypersensitivity
hypersensitivity

The common allergy

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Anaphylaxis
Anaphylaxis can
can be
be fatal
fatal

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Many
Many organ
organ are
are be
be affected
affected by
by
“allergy”
“allergy”

The nasohprynx

Rhinorrhea

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Many
Many organ
organ are
are be
be affected
affected by
by
“allergy”
“allergy”

The nasohprynx

Nasal polyps

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Many
Many organ
organ are
are be
be affected
affected by
by
“allergy”
“allergy”

The nasohprynx

Tonsillitis

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Many
Many organ
organ are
are be
be affected
affected by
by
“allergy”
“allergy”

The skin

Urticaria
(hives)

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Many
Many organ
organ are
are be
be affected
affected by
by
“allergy”
“allergy”

The skin

eczema

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 Many
Many organ
organ are
are be
be affected
affected by
by
“allergy”
“allergy”

The eye

conjunctivitis

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Many
Many organ
organ are
are be
be affected
affected by
by
“allergy”
“allergy”

The lungs

asthma

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Many
Many organ
organ are
are be
be affected
affected by
by
“allergy”
“allergy”

The GI tract

Vomiting and diarrhea

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Sensitization
Sensitization against
against allergens
allergens

pollen

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Mast
Mast cell
cell activation
activation products
products

Preformed mediators

 Histamine:
Histamine: bronchoconstriction,
bronchoconstriction, mucus
mucus
secretion,
secretion, vascular
vascular permeability,
permeability, vasodilatation
vasodilatation

 Tryptase:
Tryptase: proteolysis
proteolysis

 Kininogenase:
Kininogenase: kinins
kinins--vascular
vascular permeability,
permeability,
vasodilatation,
vasodilatation, edema
edema
 ECFA:
ECFA: attract
attract neutrophils
neutrophilsand
andbasophils
basophils

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 Mast
Mast cell
cell activation
activation products
products
Newly formed mediators

➣ Leukotriene
➣
Leukotriene B4:
B4:
attract
attractneutrophils
neutrophilsand
andbasophils
basophils
➣ Leukotriene
➣
Leukotriene C4
C4&&D4:
D4:
same
sameas
asheparin
heparin
➣ Prostaglandin
➣
Prostaglandin D2:
D2:
kinins
kinins--vascular
vascularpermeability,
permeability,vasodilatation,
vasodilatation,edema
edema
➣ PAF:
➣
PAF:
platelet
plateletaggregation,
aggregation,microthrombi
microthrombiformation,
formation,heparin
heparinrelease
release

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The
The activators
activators of
of mast
mast cells
cells

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 Allergy
Allergy symptoms
symptoms and
and cAMP
cAMP

cAMP
-agonist -agonists
(epinephrine, isoproterenol) phenyl epinephrine, nor-
-blocker epinephrine
(phenoxybenzamine) -blocker
Phosphodiasterase (propanolol)
inhibitor
(theophylline)

Relief from symptoms Worsening of symptoms

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Skin
Skin test
test for
for allergy
allergy

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Skin
Skin test
test for
for allergy
allergy

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 Laboratory
Laboratory tests
tests for
for allergy
allergy

Total IgE:
Competitive solid phase EIA
Or allergen specific IgE
Using wells coated with
the allergen

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 IgE
IgE levels
levels in
in immediate
immediate
hypersensitivity
hypersensitivity
Atopic diseases Helminthic
allergic asthma
allergic eczema
(worm)
hay fever infections

IgE

Immunodeficiency Miscellaneous diseases

 hyper-IgE syndrome  Bronchopulmonary

 Wiscott-Aldrich  aspergillosis
syndrome  IgE myeloma

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 Treatments
Treatments for
for allergy
allergy

➣ Symptomatic
➣ Symptomatic
Receptor
Receptorblockers
blockers
histamines
histamines
Leukotriene
Leukotriene
Bronchodialators
Bronchodialators

-agonists
-agonists
➣ Prevent
➣ Prevent mast
mast cell
cell degranulation
degranulation
Ca
Cainflux
influxinhibitor
inhibitor (chromolyn
(chromolyn sodium)
sodium)
Phosphodiesterase
Phosphodiesterase(theophylline)
(theophylline)
➣ Immunotherapy
➣ Immunotherapy (hyposensitization)
(hyposensitization)

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Hyposensitization
Hyposensitization

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Principles
Principles of
of immunotherapy
immunotherapy

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Type
Type IIII hypersensitivity
hypersensitivity
mechanism
mechanism

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Type
Type IIII hypersensitivity
hypersensitivity
role
role ofof neutrophils
neutrophils

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 Examples
Examples of
of type
type IIII
hypersensitivity
hypersensitivity

Most autoimmune
diseases with
autoantibody
involvement

Immunofluorescent staining
of desmosomes in pemphigus
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Type
Type IIII hypersensitivity
hypersensitivity induced
induced
by
by exogenous
exogenous agents
agents

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Examples
Examples of of drug-induced
drug-induced
type
type IIII hypersensitivity
hypersensitivity
➣ Red
➣ Red cells:
cells:
Penicillin,
Penicillin, chloropromazine,
chloropromazine, phenacetin
phenacetin

➣ Granulocytes:
➣ Granulocytes:
Quinidine,
Quinidine, amidopyridine
amidopyridine

➣ Platelets:
➣ Platelets:
sulphonamides,
sulphonamides, thiazides
thiazides

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 Pattern
Pattern of of staining
staining in
in
type
type IIII hypersensitivity
hypersensitivity

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 Type
Type III
III hypersensitivity
hypersensitivity

Serum
sickness
mediated
by immune
complexes

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 Types
Types of
of immune
immune complex
complex
disease
disease

cause antigen site of deposition

persistent bacterial, viral, infected organ,
infection parasitic, etc. kidney

inhaled antigens mold, plant or lung

animal antigen

injected material serum kidney, skin, arteries, joint

autoimmunity self antigen kidney, joint, arteries, skin

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Serum
Serum sickness
sickness

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Systemic
Systemic lupus
lupus erythematosus
erythematosus

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 Arthus
Arthus reaction
reaction

Arthus reaction Weal & flare reaction

Type-II Type-I

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Type
Type III
III hypersensitivity
hypersensitivity
mechanism
mechanism

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 Type
Type III
III hypersensitivity
hypersensitivity
the
the role
role of
of immune
immune complex
complex size
size

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Detection
Detection of
of immune
immune complexes
complexes
in
in tissue
tissue

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Detection
Detection of
of immune
immune complexes
complexes
in
in serum
serum

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Detection
Detection of
of immune
immune complexes
complexes
in
in serum
serum

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Type
Type IV
IV hypersensitivity
hypersensitivity

➣
➣ Delayed
Delayed reaction
reaction
➣
➣ 36
36 to
to48
48hours
hours
➣
➣ Characterized
Characterizedby byinduration
induration
and
anderythema
erythema
➣
➣ Also
Also known
known asas cell
cell
mediated
mediated hypersensitivity
hypersensitivity
➣ Tuberculin
➣ Tuberculin test
test is
is the
the most
most
common
common example
example

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Tuberculin
Tuberculin test
test

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Contact
Contact dermatitis
dermatitis vs
vs tuberculin
tuberculin
reaction
reaction

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Poison
Poison ivy
ivy // poison
poison oak
oak reaction
reaction

active hapten molecule

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Contact
Contact dermatitis
dermatitis reaction
reaction to
to
leather
leather

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Contact
Contact dermatitis
dermatitis reaction
reaction to
to
mango
mango sap
sap

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Old
Old Milwaukee
Milwaukee helps?
helps?

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No!
No! but
but itit makes
makes them
them feel
feel better
better

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Granuloma
Granuloma in
in aa leprosy
leprosy patient
patient

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 Delayed
Delayed hypersensitivity
hypersensitivity
reactions
reactions
type time of clinical histology antigen and site
reaction appearance

contact 48-72 eczema T cells, later epidermal: heavy

dermatitis hours macrophages metals, poison
ivy, rubber, latex

tuberculin 48-72 local lymphocytes, intradermal:

hours induration monocytes tuberculin,
lepromin, etc.
granuloma 21-28 hardening M, giant cells, persistent antigen
days epitheloid cells, stimulus, chronic
fibroblasts infection

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Mechanism
Mechanism of
of damage
damage inin contact
contact
hypersensitivity
hypersensitivity

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Type
Type IV
IV hypersensitivity
hypersensitivity
the
the three
three forms
forms

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 Comparison
Comparison of
of hypersensitivity
hypersensitivity
reactions
reactions
characteristic Type-I Type-II Type-III Type-IV
antibody IgE IgG, IgM IgG, IgM none
antigen Exogenous cell surface soluble cellular
response 15-30 min. Min.-hrs 3-8 hours 48-72 hours
time or longer
appearance Weal & flare Lysis & Erythema Erythema &
necrosis & edema induration

histology baso- and Ab and PMN and Monocytes &

eosinophils complement complement lymphocytes
transfer with antibody antibody antibody T-cells
hay fever, pemphigus, farmers’ TB test, poison
examples asthma Goodpasture lung, SLE ivy, granuloma

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