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Type 1

Group 5:
Garcia, Vixienne Geia
Natividad, Justine
Nicdao, Jan Kevin
 Type I hypersensitivity
reactions result from the
binding of antigen to
antigen-specific IgE bound
to its Fcreceptor,
principally on mast cells.
This interaction causes the
degranulationof mast cells
and the release of
inflammatory mediators.
Type I reactions are
commonly caused by
inhaled particulate
antigens, of which plant
pollens are good
examples. Type I reactions
have effects on varying
severity, ranging from a
running nose to breathing
difficulties and even death
by asphyxiation.

. Type I hypersensitivity
reactions are also
described as immediate
hypersensitivity because
they occur immediately on
exposure to antigen.

Type 1
Substances that can give
rise to wheal and flare
responses in the skin and
to the symptoms of allergic
disease are derived from
many different sources.
Almost all are protiens
10 000 to 40 000 Daltons
freely soluble in aqueous
Biological functions
(digestive enzymes, carrier
proteins, calycins and
pollen recognition
Classified by:
• Source
• Route of Exposure
• Nature of Specific Protein

Common sources of allergens
Inhaled Materials
Plant pollens
Dander of domesticated animals
Mold spores
Feces of very small animals
e.g., house dust mites

Injected Materials
Insect venoms
Therapeutic proteins

Ingested Materials
Orally administered drugs
Contacted Materials
Plant leaves
Industrial products made from plants
Synthetic chemicals in industrial
 Atopy
• a hereditary
predisposition to the
development of the
reactions against
Immunoglobulin E
The B-cell response leading
to production of IgEoccurs
in 2 stages. In the first
stage, a resting B-cell
switches from IgD/IgM
production to
IgEproduction under the
influence of IL-4. Th2 cells
produce IL-4 and Th1 cells
produce IFN-y, which has
an opposing effect.
Immunoglobulin E
 The ratio of Th1 to Th2 cells
engaged in an immune
response probably
determines the level of
IgEproduced. The second
stage of IgE response
proceeds when an IgE-
producing B cell develops
into a plasma cell. This is
controlled by cell surface
protein called Fc€RII or
CD23. Fc€RII links the B-cells
to dendritic cells and so
prevents their destruction by
Immunoglobulin E
 They are thus free to
differentiate into
plasma cells. Fc€RII
expression is
regulated by the
presence of IL-4,
which stimulates its
production, and by
IgE, which suppress
its production.

Mast Cells
There are two
populations of mast
cells in rodents and
humans: connective
tissue mast cells and
mucosal mast cells.

Mast Cells
Connective tissue mast cells
arise from precursors in
fetal liver and bone

Connective tissue mast cells
contain many uniform
granules and are rich in
histamine and heparin.

Mast Cells
Mucosal mast cells have
abundant chondroitin
sulphate and little
histamine in their

Mucosal mast cell proliferate
in response to IL-3
produced by Tcells.

Peripheral blood
basophilsshould not be
considered simply as
circulating mast cells.
They may, however, be
passively sensitized with
IgE, and they will respond
to antigen in a manner
apparently similar to that
of mast cells.

IgE binding Fc
 The reaginic activity of
IgE depends on its ability
to bind to a receptor
specific for the Fcregion of
the € heavy chain. There
are 2 types of IgE receptor:
high affinity (Fc€RI) and
low affinity (Fc€RII or

IgE binding Fc
High affinity receptor Low affinity receptor
(Fc€RI) (Fc€RII or CD23)
•Mainly found on mast •Found on NK cells,

cells and basophils, where macrophages, dendritic

there are from 10^4 to cells, eosinophils and
10^5 per cell platelets
•Multichain receptor •Is as selectin and is thus

consisting of one alpha the only known Ab

chain (45-65 kDa) that receptor that do not
binds IgE, and beta chain belong to the
(32 kDa), and 2 disulfide immunoglobulin
linked y chains (20 Kda) superfamily
that are required for
signal transduction
IgE Crosslinkage
Initiates Degranulation
 The biochemical events that
mediate degranulation of
mast cells and blood
basophils have many
features in common.
 Although mast cells
degranulation generally is
initiated by allergen
crosslinkage of bound IgE, a
number of other stimuli can
also initiate the process,
including the anaphylatoxins
(C3a, C4a and C5a) and
various drugs.
 IgE-mediated
degranulation begins
when an allergen
crosslinks IgE that is
bound (fixed) to the Fc
receptor on the surface
of a mast cell or
basophil. In itself, the
binding of IgE to
Fc€RIapparently has no
effect on a target cell.
It is only after allergen
crosslinks the fixed IgE-
receptor complex that
The importance of
crosslinkage is
indicated by the
inability of
which cannot cross link
the fixed IgE, to trigger

Pharmacologic Agents
that Mediate Type I
• Most of biologic effects
of histamine in allergic
reactions are mediated
by the binding of
histamine to H1
receptors. This binding
induces contraction of
intestinal and bronchial
smooth muscles,
increased permeability
of venules, and
increased mucus
secretion by goblet
Pharmacologic Agents
that Mediate Type I
• Interaction of histamine
with H2 receptors
dilation and stimulates
exocrine glands.
Binding of histamine to
H2 receptors on mast
cells and basophils
degranulation; thus,
histamine exerts
negative feedback on
Pharmacologic Agents
that Mediate Type I
Leukotrienes and
• As secondary mediators,
they are not formed until
the mast cell undergoes
degranulation and the
enzymatic breakdown of
phospholipids in the
plasma membrane
• An ensuing enzymatic
cascade generates the
prostaglandins and the
leukotrienes. It therefore
takes a longer time for
biological effects of these
mediators to become
Pharmacologic Agents
that Mediate Type I
Leukotrienes and
• Their effects are more
pronounced and longer
lasting, however, than
those of histamines.
• Leukotrienes mediate
increased vascular
permeability, and mucus
• Prostaglandin D2 causes

Pharmacologic Agents
that Mediate Type I
• Human mast cells
secrete IL-4, IL-5, IL-6,
and TNF-a. These
cytokines alter the local
eventually leading to
the recruitment of
inflammatory cells such
as neutrophils and
• IL-4 increases IgE
production by B cells
Pharmacologic Agents
that Mediate Type I
• IL-5 is especially
important in the
recruitment and
activation of
• The high concentration
of TNF-a secreted by
mast cells may
contribute to shock in
systemic anaphylaxis.

Clinical Manifestations Of
Type I Hypersensitivity
Allof the clinical signs of
type I hypersensitivity
relate to the release of
vasoactive molecules from
mast cells and basophils.
The severity of these
clinical signs depends on
the number and location of
the mast cells stimulated,
and this in turn depends
on the amount and route
of antigen administration.
Clinical Manifestations Of
Type I Hypersensitivity
If the rate of release of
vasoactive molecules is
greater than the body’s
ability to respond to rapid
changes to its vascular
system, the patients
suffers from acute
anaphylaxis or
anaphylactic shock and
may die.
Clinical Manifestations Of
Type I Hypersensitivity
If, on the other hand,
antigen is administered
either locally in small
quantities or slowly, then
the clinical signs of
hypersensitivity will be
much less severe, since
the individual will have
time to compensate for the
vascular changes provoked
by the mast-cell-derived

Allergy (Hay
Fever/Allergic rhinitis)
Hay fever or allergic
rhinitis this results from
the reaction of airborne
allergens with sensitized
mast cells in the
conjunctivae and nasal
mucosa to induce the
release of
pharmacologically active
mediators from mast cells;
these mediators then
caused localized
vasodilation and increased
capillary permeability.
Allergy (Hay
Fever/Allergic rhinitis)
The symptoms include
watery exudation from the
mucus membranes of the
upper respiratory tract and
conjunctivae, the natural
consequence of which
include violent and often
protracted sneezing, nasal
discharge, and lacrimation.

Allergy (Asthma)
Asthma. Airborne or blood-
borne allergens, such as
pollens, dust, fumes, insect
products, or viral antigens,
trigger an asthmatic attack
(allergic asthma); in other
cases, an asthmatic attack
can be induced by exercise
or cold, apparently
independently of allergen
stimulation (intrinsic
Allergy (Asthma)
Asthma is triggered by
degranulation of mast cells
with release of mediators,
but instead of occurring in
the nasal mucosa, the
reaction develops in the
lower respiratory tract.
Airways edema, mucus
secretion and
inflammation contribute to
the bronchial constrictions
and to airway obstruction.

Allergy (Food
• Food allergy. The local
reactions to antigens in the
intestine causes smooth
muschleconstriction and
effusion of fluid. This results
in the intense discomfort
and diarrhea. The allergens
may be absorbed and cause
mast cell degranulation
elsewhere in the body.
Allergy (Food
• Thus local reactions in the
skin can cause the
development of edematous
lesions commonly called
hives or urticaria.
Respiratory symptoms such
as asthma may also develop
as a result of food allergies.
Allergy (Atopic
 Atopic dermatitis (allergic
eczema) is an inflammation
disease of skin that is
frequently associated with a
family history of atopy. The
disease is observed most
frequently in young children,
often developing during
infancy. Serum IgElevels are
often elevated. The allergic
individual develops skin
eruptions that are
erythematousand filled with