Type I hypersensitivity, also known as immediate hypersensitivity or allergy, is an IgE-mediated immune response. Upon re-exposure to an allergen, IgE antibodies bound to mast cells and basophils are cross-linked, causing the release of inflammatory mediators like histamine. This leads to symptoms of allergy such as sneezing, itching, and difficulty breathing. Allergies can be localized to specific organs like the skin or lungs, or can cause systemic anaphylaxis with a dangerous drop in blood pressure.

1. Hypersensitivity
Dr. Dalia Wehedi

2. Type I
IgE Mediated
ClassicAllergy
Type II Type III Type IV
IgG/IgM
Mediated
IgG Mediated T cell
rbc lysis
Immune
complex
Disease
Delayed
Type
Hypersensitivity
Gel and Coombs classification of hypersensitivities.

3. TYPE I Hypersensitivity
Classic allergy
•Mediated by IgE attached to Mast
cells.
• The symptoms resulting from allergic responses are known as
anaphylaxis.
• Includes: Hay fever, asthma, eczema, bee stings, food allergies.

4. TYPE I Hypersensitivity
Classic allergy
• The course of events in a type I hypersensitivity reaction,
also known as immediate-type or anaphylactic reaction
• Repeated encounter with an antigen can lead to
sensitization, in this case the activation of B cells and
class switching to IgE.
• On the following encounter with the allergen, IgE bound to
Fcε receptors on mast cells are crosslinked by the
allergen, leading to mast cell degranulation with secretion
of histamine and chemoattractant.

5. TYPE I Hypersensitivity
Classic allergy
• The resulting inflammation is initially characterized by
histamine-induced hyperemia and edema (redness and
swelling), later by a cellular infiltrate accentuated by
eosinophils.
• Mast cells are localized mainly below epithelia that are
entry barriers for parasites, such as skin and the mucosa
of respiratory and gastrointestinal tracts.

7. Genetic Predisposition
Type I hypersensitivity
• Candidate polymorphic genes include:
• IL-4 Receptor.
• IL-4 cytokine (promoter region).
• FcRI. High affinity IgE receptor.
• Class II MHC
(present peptides promoting Th2 response).
• Inflammation genes.

8. Allergens
• Allergens are nonparasite antigens that can stimulate a
type I hypersensitivity response.
• Allergens bind to IgE and trigger degranulation of
chemical mediators.

9. Allergens
fever!

10. Characteristics of allergens
• Small 15-40,000 MW proteins.
• Specific protein components
• Often enzymes.
• Low dose of allergen
• Mucosal exposure.
• Most allergens promote a Th2 immune.

11. Allergens
Dermatophagoides pteronyssinus
(common dust mite)
gen

12. junctions
which

14. Common components
• Allergens ○ Atopy – hereditary predisposition to development
of immediate hypersensitivity reactions to common antigens
- Allows nonparasitic antigens to induce IgE response
• IgE
- Normally lowest of all antibody classes in serum
- Half-life is 2 -3 days but once bound to mast cells or
basophils, can last for weeks
• Mast cells and basophils
• IgE binding receptors
- High affinity FcεRI(mast cell, basophil, eosinophil, monocytes,
platelets)
- Low affinity. FcεRII CD 23(activated B-cell & various cell type)
Soluble, Atopic & membrane from individuals have higher
amount of soluble IgE receptor that has been shown to increase
IgE production by B cells

15. • Mast cells, basophils, and eosinophils that are
stimulated by FcεRI cross-linking release their granular
contents (including histamine and proteases) in a process
called degranulation) they also generate and secrete
inflammatory cytokines and lipid inflammatory molecules
(leukotrienes and prostaglandins)
• Mediators Derived from Mast Cells (primary & secondary
mediators)
• Primary mediators: Biogenic Amines and proteolytic
enzymes
- Histamine acts by binding to target cell receptors (e. g. , H
1, H 2, H 3)
- The actions of histamine are contraction of the endothelial
cells, leading to increased inter endothelial spaces,
increased vascular permeability, and leakage of plasma into
the tissues and other effect cause vasodilation also causes
contraction of intestinal and bronchial smooth muscle.
proteolytic enzymes : tryptase - tissue damage

16. Mechanisms of allergic response
Sensitization
Repeated exposure to allergens initiates immune response
that generates IgE isotype.
Th2 cells required to provide the IL-4 required to get
isotype switching to IgE.
IL-4, IL-4R, CD40 and IgE
switch.

17. Mechanisms of allergic response
Sensitization (FcR)
• The IgE can attach to Mast cells by Fc receptor, which
increases the life span of the IgE.
• Half-life of IgE in serum is days whereas attached to
FcR it is increased to months.
FcR1
• high affinity IgE receptor found on
• mast cells/basophils/activated eosinophils.
• Allergen binding to IgE attached to FcR1 triggers
release of granules from cell.

18. Mechanisms of allergic response
FcRI
finity
AM

19. Mechanisms of allergic response
Effector Stage of Hypersensitivity
Secondary exposure to allergen
• Mast cells are primed with IgE on surface.
• Allergen binds IgE and cross-links to activate signal with
tyrosine phosphorylation, Ca++ influx, degranulation and
release of mediators.

20. FcRI Triggers Release of Mediators
Early mediators
cause immediate symptoms
e.g. histamine (preformed in granules)
leukotriene C4 and prostaglandin D2
are quickly made 2' mediators

23. Mediators of Type I Hypersensitivity
Immediate effects
• Histamine
• Constriction of smooth muscles. Bronchiole constriction =
wheezing. Constriction of intestine = cramps-diarrhea.
• Vasodilation with increased fluid into tissues causing
increased swelling or fluid in mucosa.
• Activates enzymes for tissue breakdown.
• Leukotrienes
• Prostaglandins

24. Continuation of sensitization
Mast cells control the immediate response.
• Eosinophils and neutrophils drive late or chronic response.
• More IgE production further driven by activated Mast cells,
basophils, eosinophils.

25. Continuation of sensitization cycle
Eosinophils
• Eosinophils play key role in late phase reaction.
• Eosinophils make
• enzymes,
• cytokines (IL-3, IL-5, GM-CSF),
• Lipid mediators (LTC4, LTD4, PAF)
• Eosinophils can provide CD40L and IL-4 for B cell
activation.

26. Localized anaphylaxis
• Digestive tract contact results in vomiting, cramping, diarrhea.
• Skin sensitivity usually reddened inflamed area resulting in
itching.
• Airway sensitivity results in sneezing and rhinitis OR wheezing
and asthma.

27. Systemic anaphylaxis
• Systemic Anaphylaxis is a systemic immediate hypersensitivity reaction characterized by
edema in many tissues and a decrease in blood pressure, secondary to vasodilation.
• These effects usually result from the systemic presence of antigen introduced by injection,
an insect sting, or absorption across an epithelial surface such as gut mucosa.
• The allergen activates mast cells in many tissues, resulting in the release of mediators
that gain access to vascular beds throughout the body.
• The decrease in vascular tone and leakage of plasma caused by mast cell mediators can
lead to a significant decrease in blood pressure or shock, called anaphylactic shock,
which is often fatal.
• The cardiovascular effects are accompanied by constriction of the upper and lower
airways, laryngeal edema treatment is systemic epinephrine, which can be lifesaving by
reversing the bronchoconstrictive and vasodilatory effects of mast cell mediators.

28. • Clinical aspects of hypersensitivity reactions:
1- Allergic rhinitis:
• Commonly termed as hay-fever.
• Caused by airborne allergen include plant pollens, dust and
animal dander etc....
• Allergen usually reacts with IgE bound to Mast cells located in
respiratory passage and conjunctiva of eyes, causing activation
and degranulation for these cells.
• Typical symptoms of allergic rhinitis include: sneezing, coughing,
nasal congestion, red eyes, itchy eyes, runny nose.
HYPERSENSITIVITY TYPE I

29. • Clinical aspects of hypersensitivity reactions:
2- Asthma:
• Common localized anaphylaxis. Chronic disease to the lower
respiratory system passages. Main and most important clinical
symptoms include airflow limitation (difficulty in breathing).
• An inflammatory disease caused by repeated immediate-type
hypersensitivity and late-phase allergic reactions in the lung
leading to the clinic-pathologic triad of intermittent and
reversible airway obstruction, chronic bronchial
inflammation with eosinophils, and bronchial smooth muscle
cell hypertrophy and hyperreactivity to bronchoconstrictors
HYPERSENSITIVITY TYPE I

30. 2- Asthma:
• The pathophysiologic sequence in atopic asthma is probably initiated
by mast cell activation in response to allergen binding to IgE as well as
by TH 2 cells reacting to allergens.
• The lipid mediators and cytokines produced by the mast cells and T
cells lead to the recruitment of eosinophils, basophils, and more TH 2
cells.
• The chronic inflammation in this disease may continue without mast
cell activation. Smooth muscle cell hypertrophy and hyperreactivity are
thought to result from leukocyte-derived mediators and cytokines.
• Mast cells, basophils, and eosinophils all produce mediators that
constrict airway smooth muscle.
• The most important of the bronchoconstricting mediators are LTC 4,
LTD 4, and LTE 4.
• Increased mucus secretion results from the action of cytokines, on
bronchial epithelial cells. Corticosteroids may also be given
systemically, especially once an attack is under way, to reduce
inflammation and bronchial smooth muscle cell relaxants
HYPERSENSITIVITY TYPE I

32. Hypersensitivity Pneumonitis (HP)
Also referred to as extrinsic allergic alveolitis.
The disease that exists in acute, subacute and chronic
forms.
It is an allergic disease in which the allergen is inhaled
in the form of an organic dust of bacterial, fungal,
vegetable, or avian origin.
Phases of the disease (sensitization and elicitation) of
the disease state generally require high-dose exposure,
prolonged exposure.
HP is rare, and most cases have been reported in
certain occupations, such as farming, painting workers.

33. Hypersensitivity Pneumonitis (HP)
The immunopathogenesis of the disease is believed to
be cell-mediated (delayed) hypersensitivity and also in
some conditions is hypersensitivity type III.
Alveolar macrophages and TH1 of CD4 cells play an
important role in the progression of the disease in early
stages. The response mostly shifts into TH2 later.
Persistence of the allergen (Ag) play a role in the
mechanism of the acute phase of the disease. HP results
in acute episodes of non-infectious, immunologically
mediated interstitial pneumonitis (ie, alveolitis), which
might eventually produce restrictive irreversible lung
disease.

34. Hypersensitivity Pneumonitis (HP)
In type III the pathology is characterized by a
bronchiolocentric interstitial mononuclear cell
infiltration, small non-necrotizing epithelioid cell
granulomas poorly formed, diffuse cellular pneumonitis
and variable degrees of pulmonary fibrosis.
Precipitins against causative antigen, IgG and
complement were found in vessel walls.
In acute HP, pulmonary parenchyma inflammation
appears to be mainly mediated by a type 3 response, as
suggested by the presence of high titers of antigen-
specific precipitating IgG in the serum, and an increase
in lung neutrophils.

35. Hypersensitivity Pneumonitis (HP)
T-lymphocytes mediated hypersensitivity response is
the most important type 4 immune reaction in the
pathogenesis of HP.
Th1-cytokine network plays a key role in the
development of HP.
Later in the chronic form develops a Th2-like immune
response.
As a result gradual increase in CD4+ T cells and in the
CD4+/CD8+ ratio, a modification toward TH2 T cell
differentiation and cytokine profile as well as a decline
of CD8+ T cells.