H Y P ER S EN S ITIV ITY

NUR FADZLINA BINTI ZABRI

082013100006
SERIAL NO 4

Introduction

A state of altered reactivity in which the

body reacts with an exaggerated
immune response to a foreign agent

Five types of hypersensitivity raections :

Type I (Anaphylactic) Reactions
Type II (Cytotoxic) Reactions
Type III (Immune Complex) Reactions
Type IV(Cell-Mediated) Reactions
Type V (Stimulatory Type)

Type III/Im m une Com plex D isease

Antigen and antibodies form complex and

escape phagocytosis.
The immune complexes deposited on
basement membrane of blood vessel.
Activate complements and induce
inflammation.
Eg : Systemic Lupus Erythematosus (SLE),
Rheumatoid Arthritis (RA)

Type IV /CellM ediated Reaction or D elayed

H ypersensitivity
Mediated by macrophages that are activated

by T Cells
Allergens are taken up by APCs and
presented to T cell.
Proliferation of T cell, some migrate to the
allergen entry into the body.
Secreted cytokines that activate
macrophages, induce inflammatory reactions.
Eg : skin test for tuberculosis.

Type V /Stim ulatory type

A modification of Type II

hypersensitivity reaction
Antibodies interact with antigens on
cell surface
Cell proliferation and differentiation

TYPE III/IM M U N E CO M PLEX REACTIO N

Deposition of antigen-antibody complex in
tissues ( vascular endothelial surfaces)
Activation of complement and infiltration
of polymorphonuclear leucocytes
Tissue damage

Immune complex reaction

Arthus
reactio
n
Serum
sickne
ss

Localized
Due to
antibody
excess
Generalized
Due to antigen
excess

i) Arthus reaction
With injection , intense local edema and
hemorrhagic necrosis develop
Tissue damage due to antigen-antibody
complex formed at equivalence or slight
antibody excess
These complex activates complement
Attract neutrophils at the local site

Arthur reaction
can be passively
transferred with
sera containing
high titre of
antibodies (IgG,
IgM)

Leucocyte-platelet thrombi formed which reduce

blood supply. Tissue necrosis occur

 Mechanism(pictures)

 Clinical types;
Hypersensitivity pneumonitis

a)

Inhalation of exogenous antigen may lead

to allergic alveolitis such as farmers lung
Caused by inhalation of spores of
thermophilic actinomycetes
Bagassosis due to allergy of sugar cane
producers to the product
Cheese-washers disease by inhaling of
penicillium casei spores

b) Hypersensitivity due to internal antigens

Living filarial worms are harmless but the
dead one may cause filariasis
By initiating inflammatory reaction
Dapsone therapy in leprematous leprosy
may also release bacterial antibody
Leads to high level of antibody production

ii) Serum sickness

Single injection of high concentration of foreign
serum
Antibodies to foreign serum reach high enough
but still excess antigen remains in the circulating
blood
Immune complexes get deposited on the
endothelial lining of blood vessel

Massive complement activation leads to fall in

complement concentration

 Characterized by :

Fever
Urticaria
Arthralgia
Lymphadenopathy
Splenomegaly
Immune complex disease :

Poststreptococcal glomerulonephritis
Endocarditis
Hepatitits B
Dengue hemorrhagic fever
Malaria
Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis (RA)

TYPE IV /D ELAYED O R CELL M ED IATED

REACTIO N
Reaction is mediated by sensitized T-

lymphocytes which on contact with

specific antigen
Delayed hypersensitivity occurs within
48-72 hours of antigen challenge
It is not antibody mediated, hence it
cannot be passively transferred by
serum
Can be transferred by lymphocytes or
transfer factor

 Types :
Tuberculin infection type
Contact dermatitis type
Granulomatous type

i) Tuberculin infection type

Small dose of tuberculin is injected

intradermally in a person sensitized to

tuberculoprotein
An erythema and induration occurs at the
site of injection
Injection site is infiltrated by large numbers
of lymphocytes and 10-20% macrophages
Purified protein derivative (PPD), an active
material of tubercle bacilli is used in
tuberculin test

 Useful indicator for delayed hypersensitivity

to bacillus
Develops in many infections with bacteria,
fungi and parasite
Various skin test are done to detect delayed
type of hypersensitivity , examples :
Lepromin test positive in tuberculoid leprosy
Frei test positive in lymphogranuloma venereum
(LPV)
Mantoux test for Tuberculosis
Histoplasmin test Positive in histoplasmosis
Patch test poison ivy

ii) Contact derm atitis type

Skin intact with a range of sensitizing
materials

Nickel,
chromium,
picryl chloride,
cosmetics,
soaps,
antibiotics

These substance acts as hapten

Cell mediated is induced in skin when
chemical is applied on an inflammed area.
Langerhans cells carry these antigens to
regional lymph node
T-lymphocytes are sensitized

Sensitized lymphocytes release

lymphokines
Cause superficial inflammation of the
skin
Characterized by redness, induration,
vesiculation within 24-48 hours
The dermis is infiltrated predominantly
by lymphocytes and few macrophages

H apten + tissue protein =

com plete antigen sensitized T lym phocytes

 Detection by patch test

Suspected allergen is applied on a small

area of skin under the adherent dressing

Sensitised individual develops itching in 4-5
hours

ii) G ranulom atous type

Results from persistence of

microorganisms or other particles

within the macrophages, which cell is
unable to destroy
Shows granuloma containing
epitheloid cells, giant cells and
macrophages
Eg : Mitsuda reaction to leprosy
antigens
Other example : Crohns disease,

DTH type

Reaction
time

Contact

48-78
hours

Tuberculin

48-72
hours

Granuloma 4 weeks
tous

Clinical
appearan
ce
Eczema

Antigen

Epidermal,
eg : nickel,
rubber,
poison ivy
Local
Intraderma
hardening l, used
and
diagnostica
swelling
lly
Hardening Persistent
, eg: in skin Ag or Agor lung
Ab
complexes

TYPE V /STIM U LATO RY TYPE

Modification of Type ll hypersensitivity

reaction
Antibodies interact with antigens on
cell surface
Lead to cell proliferation and
differentiation
Antigen-antibody reaction enhances
the activity of affected cell

 Example :

Graves disease
thyroid hormone are produced in excess
Long acting thyroid stimulating (LATS)
antibody is an autoantibody to thyroid
membrane antigen
LATS + TSH receptor on thyroid cell
surface and produce the same effect as
TSH
Hence, excessive secretion of thyroid
hormone

SH W ARTZM AN REACTIO N
Not an immune response
It has superficial resemblance of

hypersensitivity reaction
ls a rare reaction of a body to
particular types of toxins, called
endotoxins, which causethrombosis
in the affectedtissue.

1. S. typhi is
injected
intradermally
Hemorrhagic
necrotic lesion is
developed
Initial intradermal
(preparatory)
injection cause
accumulation of
leucocyte
Release of
lysosomal enzyme
damage capillary
wall

2. Same filtrate
is injected
intravenously
after 24 hours
Intravenous
(provocative)
injection, there
occurs intravascular
clotting
The thrombi
leading to necrosis
of vessel walls and
hemorrhage

Both preparatory and

provocative doses are given
intravenously

Animal dies within 12-24

hours

Due to bilateral cortical

necrosis of the kidney and
patchy hemorrhagic necrosis
in other organs

Reaction known as SanarelliShwartzman raection

Contact with large

quantities of
lipopolysaccharide
endotoxin

Excessive release
of cytokine (TNF
and IL1-6)
Massive activation
of complement by
the alternative
pathway

Release of
thromboxane A2 and
prostaglandins from
platelets

Disseminated
intravascular
coagulation

 This mechanism operate in certain

clinical conditions such as,

Fulminating meningococcal septicemia
Acute hemorrhagic adrenal necrosis

found in overwhelming infections

(Waterhouse-Friederichsen Syndrome)
Neisseria meningitidis endotoxin

REFEREN CES
Textbook of Microbiology 8th Edition

by Ananthanarayan and Panikers

Textbook of Microbiology by Prof. CP
Baveja
Immunology, International Edition 7th
Edition by David Male, Jonathan
Brostoff
Text Book of Microbiology by P.
Chakraborty
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