Hypersensitivity

 Hypersenitivitystate is the
undesirable effects of the specific IR
following re-exposure to an antigen in
a genetically susceptible individual.
Classification

 Gell and Coombs described 4 types

of hypersensitivity
reactions(typeI,II,III and IV).
 The first 3 types are antibody-
mediated and the fourth is mediated
primarily by T cells and
macrophages.
Anaphylactic Reaction

 When a hypersensitive person is

exposed to an antigen(allergen) a
cytophilic antibody IgE is formed in
excess and can bind toFc receptors
on mast cells and basophils
(sensitized cells).
 Thesensitized cell appears to
present a number of IgE Fab
fragments,and to initiate a response,
antigen must bind to two
independent fragments forming IgE-
antigen-IgEbridge.
 Withinminutes, this binding causes
the mast cells to degranulate,
releasing certain preformed
mediators stored in mast cell
granules specially histamine, as well
as bradykinin and slow reacting
substances of
anaphylaxis,subsequently the
degranulated cell begins to
synthesize and release additional
 The result is two phase response;
 1-An initial phase which has an
immediate effect on blood vessels,
smooth muscles and glandular
secretion, this phase is characterized
grossly by erythema, localized
edema and pruritis.
 2-Thesecond phase is followed few
hours later by cellular infiltration
(eosinophils and neutrophils) of the
involved site.
 Inman there are two types of
anaphylactic reaction, systemic and
local which are related to the mode
of entry in the body of the shocking
dose of antigen.
 If the antigen is injected parentrally,
as in case of foreign serum (e.g.
horse anti-tetanic serum), a drug
such as penicillin, or by insect bite,
the systemic form of anaphylaxis is
likely to develop.
 Thesymptoms include dyspnea with
bronchospasm and peribronchial and
laryngeal oedema, sometimes skin
rashes, a fall in blood pressure and
occasionally death.
 If,on the other hand, the antigen
comes in contact with respiratory
mucous membrane, in a sensitized
individual (atopic patient), the local
form of anaphylaxis will
develop,i.e.hay fever or asthma.
 Ifthe appropriate antigen (e.g.
nuts,egg,chocolate,fish or
strawberries), comes in contact with
the intestinal mucous membrane of a
susceptible individual, a mixed form
of reaction may develop;
vomiting,diarrhoea and skin
rashes(urticaria).
Prevention of Anaphylaxis
(Desensitization)
 Consideration of the mechanism of
systemic anaphylaxis makes it seems
likely that if the parenterally injected
antigen could be prevented from
reaching the tissue-fixed IgE,then
anaphylaxis would not develop.
 Thiscan be achieved by injecting
frequent small doses of the antigen
to which the patient is sensitized; this
induces the formation of increased
levels of IgG antibody which by
circulating in the blood and tissue
fluids,mops up the injected antigen
so that it does not reach the tissue
fixed IgE.
 The IgG antibody has been termed
blocking antibody and its induction is
the basis of desensitization treatment
of allergic individuals.
 Treatment of
Anaphylactic
Reactions
 This is designed to counteract the
effect of released chemical mediators
or to block their action.
 In systemic anaphylaxis, the main
efforts are directed at maintaining
ventilation and cardiac function,
epinephrine is given subcutaneously.
 Corticosteroids may be administered.
 Hypersensitivity Test

 The following test should be done for

persons that need treatment with a
foreign protein as horse serum, or a
drug such as penicillin to detect if the
person is sensitive or not to this
allergen.
Skin test

 0.1 ml of the diluted antigen is

injected intradermally in the flexor
surface of the arm.
 A reaction in the form of oedema
surrounded by a zone of erythema
about 2-10 cm appears in a few
minutes and disappears in 20-60
minutes.
Cytolytic or Cytotoxic
reaction
 Reactions of this type are initiated by
an antigenic component that is
either:
 1-Part of a tissue cell(e.g.:antigens of
the ABO group and Rh antigen) or
 2-A foreign antigen closely
associated with a cell(e.g.: drug
attached to the cell wall).
 The antibodies (IgM or IgG) directed
against such a cell associated
 Mechanisms of action

 A-Complement mediated lysis

Antibody directed at cell surface
antigens activates complement to
damage the cells.
The antibody (IgG or IgM) attaches to
the antigen via Fab region and so
complement will attach to the Fc
portion of the antibody causing cytolytic
effect on the cells, as occurs in
haemolytic aneamias, incompatible
blood transfusion and Rhesus (Rh)
B-Phagocytosis

 The antibody (opsonin) bound to the

cell antigen leading to opsonization
which will enhance phagocytosis.
C-Antibody dependent
cellular
cytotoxicity (ADCC)
 This is a process different from
phagocytosis and independent of
complement.
 The antibody coated cells can be
killed by several numbers of cells as
natural killer cells which possess Fc
receptor for IgG and therefore can
interact and cause cytotoxic damage
to target cells.
 This cytotoxic activity occurs on
Type 2 hypersensitivity
 Toxic Complex
Syndrome
(Type III-
 These reactions are due to
combination of antigen with
circulating antibody (Ig G) leading to
formation of microprecipitates in and
around small blood vessels with
consequent inflammation and
sometimes mechanical blockage of
the vessels, causing interference with
blood supply to surrounding tissues.
 There are two types of reaction that
fall into this category;

A systemic form or serum sickness.

A local form or Arthus reaction.

 Serum sickness, develops in
individuals given injections of large
amounts of foreign serum or drugs as
penicillin which is eliminated from
the circulation over a period of few
weeks.
 The symptoms are dependent on
deposition of immune complexes
( antigen+ IgG antibody)
in blood vessels which activate
complement and cause inflammatory
changes.
 Typical serum sickness results in
fever, urticaria, arthralgia,
lymphadenopathy, splenomegaly and
eosinophilia a few days to 2 weeks
after injection of foreign serum or
drug.
 The symptoms disappear whenever
all the foreign antigen is eliminated.
 Arthus reaction, like serum sickness,
is brought about by formation of
complexes but in this case the
phenomenon is a localone at the site
of injection of antigen.
 Arthus reaction occurs in walls of
small blood vessels in the presence
of large quantities of IgG antibody
which form microprecipitates with
antigen.
 Vasculitis develops a few hours after
injection
and persists for 12 to 24 hours.

Liberation of vasoactive amines

such as histamine causes an increase
in vascular permeability and
consequent oedema.
 These reactions may occur in
diabetics who have received many
intradermal injections of insulin and
have developed high levels of IgG
antibody to antigenic constituents in
insulin preparation.
Delayed
Hypersensitivity(Type IV or
cell mediated
 These reactions are characteristically
induced by intracellularinfectious
agents including salmonella,
brucella, mycobacteria, pathogenic
fungi, and a wide range of viruses.
 This
form of hypersensitivity reaction
may be defined as a specifically
provoked, slowly evolving (48 hours),
mixed cellular reaction particularly
lymphocytes and macrophages.
The classical example of this type of
reaction is the tuberculin response
which occurs when an individual
previously infected with tubercle
bacilli is given an intradermal
injection of 0.1 ml of protein extract
of tubercle bacilli ( purified protein
derivative or PPD), 48 hours later an
indurated inflammatory reaction of
variable size can be seen in the skin.
 Thereaction is initiated by activation
of antigen specific Th-cells, which
then release lymphokines. These
compounds together with bioactive
substances released by antigen
presenting cells serve to attract
additional inflammatory cells from
the circulation.
 Some of the lymphokines promote
differentiation and activation of
macrophages and so enhance the
phagocytic, and bactericidal function
of these cells.
 Delayed hypersensitivity reactions
sometimes develop after
sensitization to a variety of metals
such as nickel and chromium.
 Skin sensitization to penicillin is not
uncommon after the topical
application of antibiotic in ointments
or creams.
 These substances are not themselves
antigenic and only become so on
combination by covalent bonds with
proteins in the skin.
 The clinical signs induced in these
contact hypersensitivity reactions
( contact dermatitis) include redness,
swelling, vesicles, scaling and
exudation of fluid.
Type IV hypersensitivity
Delayed hypersensitivity