3. These reactions may be damaging,
uncomfortable or occasionally fatal
Hypersensitivity reactions require a pre-sensitized
(immune) state of the host
4. IMMUNITY
INNATE ( NATURAL)
Refers to mechanisms that are ready to react to
infections even before they occur
ADAPTIVE
Refers to the mechanisms that are stimulated by
microbes and capable of recognizing microbial and
non-microbial substances
6. CYTOKINES/CHEMOKINES
CYTOKINES
• Are proteins produced by many cells (usually
lymphocytes and macrophages)
• Plays numerous roles in acute and chronic inflammation
and immunity
• TNF, IL-1by macrophages
• Mediate innate (natural) immunity (IL-1, TNF,
Interferons)
7. • Activate inflammatory cells
• Regulate lymphocyte growth (many interleukins, IL-
2,IL-4,IL-5,IL-17 and INFᵞ)
• Stimulate hematopoesis (Colony Stimulating Factors)
CHEMOKINES
• Are small proteins which are attractants for PMNs
8. ADAPTIVE IMMUNITY
➢ It is developed by exposure to pathogens or in a
broader sense antigens not recognized by the MHC
(MHC-Major Histocompatibility Complex)
➢ It’s major job is to make sure all self cells are
recognized and tolerated because the general rule
of the immune system is that all un-recognized will
not be tolerated
9. TYPES OF ADAPTIVE IMMUNITY
CELLULAR – Mediated by T lymphocytes i.e.
direct cellular reactions to antigens
HUMORAL- Mediated by B lymphocytes and their
products i.e. antibodies (immunoglobulin)
10. CELLS OF THE IMMUNE SYSTEM
➢ T Lymphocytes
➢ B Lymphocytes
➢ Plasma Cells (modified B Cells)
➢ Macrophages
➢ Dendritic Cells
➢ NK (natural killer) Cells
11. ➢ APCs (Macrophages, Dendritic Cells)
➢ T-LYMPHOCYTES
• Helper T Lymphocytes(CD4+T CELLS)
• Cytotoxic T Lymphocytes(CD8+T CELLS)
• Regulatory T Lymphocytes
➢ B-Cells→ Plasma Cells→ AB’s
➢ NK Cells
FUNCTIONS OF IMMUNE SYSTEM
13. HYPERSENSITIVITY
GELL’S AND COOMBS CLASSIFICATION
➢ Type I (IgE-mediated)
(anaphylactic or atopic reaction)
➢ Type II (Cytotoxic reaction)
➢ Type III (Immune complex-mediated)
➢ Type IV (Delayed-type hypersensitivity)
(T cell mediated reaction)
14. ANOTHER CLASSIFICATION
1. IMMEDIATE TYPE
➢ Reaction occur immediately (within sec. to minutes)
➢ Mediated largely by humoral antibodies
➢ Include Type-I,II,III.
2. DELAYED TYPE
➢ Slower in onset (within 24-48 hrs)
➢ Mediated largely by cellular response
➢ Include Type-4.
15. Type I Hypersensitivity is defined as a rapidly developing
immunologic reaction occurring within minutes after
the combination of an antigen with IgE antibody bound
to mast cells or basophils in individuals previously
sensitized to the antigens.
TYPE I HYPERSENSITIVITY REACTION
16. • IgE's main function is to
provide immunity against parasites
•IgE also plays an essential role in type I
hypersensitivity, which manifests various allergic
diseases
• Immunoglobulin E (IgE) is a class
of antibody that has been found only in
mammals
18. BASOPHILS
Basophils are the
circulating
counterparts of mast
cells
They also express
FcεRI but their role in
most immediate
hypersensitivity
reactions is not
established (since
these reactions occur
in tissues and not in
the circulation)
19. •The primary cellular component in this
hypersensitivity is the mast cell or basophil.
•The reaction is amplified or modified by
platelets, neutrophils and eosinophils
20. MAST
CELLS
➢ Mast cells are derived from
precursors in the bone
marrow and are widely
distributed in tissues and
often reside near blood
vessels and nerves and in
sub-epithelial locations
➢ Mast cells express a high-
affinity receptor for the Fc
portion of the ε heavy chain
of IgE called FcεRI
21. SENSITIZATION AGAINST ALLERGENS
AND TYPE-I HYPERSENSITIVITY
B
cell
Histamine,
tryptase,
kininegenase,
ECFA
Leukotriene-B4, C4, D4,
prostaglandin D, PAF
Newly
synthesized
mediators
TH2
Mast cells
Plasma
cell
IgE
22.
23. • Type I reaction are mediated by IgE antibodies.
• The differentiation of IgE- secreting B cells is highly
dependent on the induction of CD4+ helper T cells of the
TH2 type. Hence, TH2 cells are pivotal in the
pathogenesis of type I hypersensitivity.
• The first step in the synthesis of IgE is the presentation of
the antigen to the precursors of TH2 cells by antigen-
presenting dendritic cells.
• The newly minted TH2 cells produce a cluster of
cytokines, including IL-3,IL-4, IL-5, and GM-CSF.
• IL-4 is absolutely essential for turning on the IgE-
producing B cells and for sustaining the development of
TH2 cells.
24. • IL-3, IL-5, and GM-CSF promote the survival of
eosinophils, which are important effectors of type I
hypersensitivity.
• IgE antibodies have a strong tendency to attach to mast
cell or basophil, armed with cytophilic IgE antibodies, is
re-exposed to the specific allergens, a series of reaction
takes place, leading eventually to the release of variety of
powerful mediators responsible for the clinical expression
of type I hypersensitivity reaction.
25.
26. • In the first step in the sequence, antigen is bound to the
IgE antibodies previously attached to the mast cells.
• In this process, multivalent antigens bind to more than
one IgE molecules and cause cross-linking of adjacent
IgE antibodies.
• The bridging of IgE molecules activates signal
transduction pathways from the cytoplasmic portion of
the IgE Fc receptors.
27. • These signals initiate two parallel and inter-dependant
processes- one leading to mast cell degranulation with
discharge of preformed (primary) mediators and the other
involving synthesis and release of secondary mediators,
such as Arachidonic metabolites.
• These mediators are directly responsible for the initial,
sometimes explosive symptoms of type I hypersensitivity,
and they also set into motion the events that leads to the
late-phase response.
29. PREFORMED (PRIMARY) MEDIATORS
WITH THEIR FUNCTION
Biogenic amines (Histamine &
Adenosine)
Histamine: Bronchial smooth
muscles contraction, increase
secretion of nasal, bronchial,
and gastric glands, increase
vascular permeability
Adenosine: Release mast cell
mediator, bronchoconstriction
and inhibits platelets
aggregation
Chemotactic mediators
Eosinophil and Neutrophil
chemotactic factor
30. PREFORMED (PRIMARY) MEDIATORS
Enzymes (proteases- chymase,
tryptase & several acid
hydrolase)
Generation of kinins and
activates components of
complement (C3a)
Proteoglycans (Heparin
chondroitin)
Serve to packaging and store the
other mediators in the granules.
31. NEWLY FORMED (SECONDARY) MEDIATORS
WITH FUNCTION
Leukotrienes B4
Highly chemotactic for
Neutrophil, Eosinophils and
Monocytes.
Leukotrienes C4, D4
• Most potent vasoactive and
spasmogenic agents.
• 1000x more potent than
Histamine in increasing vascular
permeability and causing
bronchial muscle contraction
32. NEWLY FORMED (SECONDARY) MEDIATORS
WITH FUNCTION
prostaglandins
D2
• Most abundant mediator derived by the
cyclooxygenase pathways in mast cells.
• It causes intense bronchospasm as well as
increased mucus secretion.
PAF (platelet-
activating factor)
• Help in Platelet aggregation, release
Heparin, bronchospasm, increased vascular
permeability, and vasodilation.
• Has important pro-inflammatory actions.
•Chemotactic for neutrophils and eosinophils.
33. NEWLY FORMED (SECONDARY) MEDIATORS
WITH FUNCTION
Cytokines (TNF-
α, IL-1, IL-3,IL-
4,IL-5,IL-6 and
GM-CSF)
• Plays important role in pathogenesis of
hypersensitivity I reaction because of their
ability to recruit and activate inflammatory
cells.
• Mast cells produce variety of cytokines and
chemokines as macrophage inflammatory
protein (MIP)-1α and MIP-1β.
• They promote IgE secretion and Eosinophil
accumulation
34. ACUTE PHASE ALLERGIC
REACTION
➢ Histamine and leukotrines released rapidly from
sensitized mast cells are responsible for the intense
immediate reaction
➢ Occurs within seconds to minutes of IgE receptor
activation (mast cell mediator release) and resolves
within an hour
➢ S/S: Vasodilation, vascular leakage, edema, mucus
secretion, and smooth muscle spasm
35. LATE PHASE ALLERGIC REACTION
A delayed inflammatory response (peaking at 2-8 hrs
and persisting up several days) following an intense
acute phase reaction
➢ Skin: Erythema, Induration, Burning
➢ Lungs: Airway Obstruction
➢ Nose/eyes: Erythema, congestion, burning
Is characterized by more intense infiltration of tissues
with eosinophils, neutrophils, basophils, monocytes
and CD4+T cells as well as tissue destruction in the
form of epithelial cell damage.
36. Inflammatory cells release additional waves of mediators,
that cause epithelial cell damage.
Epithelial cell also produce soluble mediators as IL-6,IL-8
and GM-CSF.
Eosinophils are important cells among the cells that are
recruited in the late-phase reaction.
Their survival in tissues is favoured by cytokines (IL-3, IL-5
and GM-CSF).
Chemokines Eotaxin and RANTES released from activated
epithelial cells under the influence of mediators (TNF-α)
promote eosinophil chemotaxis.
37. Collection of eosinophils is as extensive as that of mast
cells, and in addition they produce major basic protein
and eosinophil cationic protein, which are toxic to
epithelial cells.
Activated eosinophils and other leukocytes also produce
leukotriene C4 and PAF and directly activate mast cells
to release mediators.
Thus, the recruited cells amplify and sustain the
inflammatory response without additional exposure to
the triggering antigen.
Late-phase inflammatory response is a major cause of
symptoms in type I hypersensitivity.
38. SUMMARY OF THE ACTION OF MAST CELL
MEDIATORS IN TYPE I HYPERSENSITIVITY
ACTION MEDIATOR
Cellular infiltration Cytokines, e.g. TNF-α,
Leukotriene B4, eosinophil
chemotactic factor of
anaphylaxis, Neutrophil
chemotactic factor of
anaphylaxis, PAF
Vasoactive (vasodilation,
increased vascular
permeability)
Histamine, PAF, LeukotrienesC4,
D4, E4, Neutral proteases that
activate complement and kinins,
Prostaglandin D2
Smooth muscle spasm Leukotrienes C4, D4, E4,
Histamines, Prostaglandins, PAF
39. Diagnostic tests for immediate
hypersensitivity
➢Skin (prick and intradermal) tests
➢ Measurement of total IgE and Specific IgE
antibodies against the suspected allergens
40. EXAMPLES OF TYPE 1
HYPERSENSITIVITY
➢ BRONCHIAL ASTHMA
➢ ALLERGIC RHINITIS
➢ ANAPHYLAXIS
(systemic and Local)
➢ ALLERGIC CONJUNCTIVITIS
➢ URTICARIA
➢ HAY FEVER
➢ ALLERGIC GASTROENTERITIS