Transcript Hypersensitivity reactions

Hypersensitivity reactions
Overview
• Hypersensitivity, allergic reaction
– similar to protective mechanisms
– exaggerated and damaging to host
• Antigens = allergens
• Classified into 4 types (Gell & Coombs)
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Type I : Anaphlylactic reaction
Type II : Cytolytic, cytotoxic reaction
Type III : Immune complex reaction
Type IV : Cell-mediated immunity (CMI), Delayed type
hypersensitivity (DTH)
Hypersensitivity reactions:
Antibody-mediated (type 1) reactions
Anaphylactic reaction
• Anaphylaxis (Portier & Richer)
– Glycerin extract of sea anemone induced exaggerated
response on 2nd injection
– ‘ana’ = away from, ‘pro’ = toward, ‘phylaxis’ = protection
• Mediated by IgE Ab - bind through Fc portion with
Fce receptors on mast cells & basophils
• Three phases
– Sensitization : IgE production upon Ag stimulation &
binding of Fc on mast cells & basophils
– Activation : Re-exposure to Ag & granule release
– Effector : Anaphylaxis due to pharmacologic activity of
released agents
General mechanism underlying type I hypersensitivity
Figure 14.1
Electron micrograph of a normal mast cell illustrating the large monocytelike nucleus and the electron-dense granules. On the right, a mast cell has
been triggered and is beginning to release the contents of its granules, as
seen by their decrease in opacity and the formation of vacuoles
connecting with the exterior. [Photographs courtesy of Dr. T. Theoharides,
Tufts Medical School.]
Sensitization
• Exposure to allergens by mucosal contact,
ingestion or parental injection resulting in IgE
production
• 50% of population produce IgE to air-borne
allergens, only 10% develop clinical symptoms
– ‘atopy’ (uncommon) = unique, unexpected response
– atopic = affected patients
• IgE production = T-dep. (TH2 cells - IL4)
• Low level of IgE in non-allergic individuals = Ts &
TNF-a
Skin testing by intradermal injection of allergens into the forearm
Activation
• Triggering of mast cells to release granules &
pharmacologically active components
• Requires bridging of at least 2 receptors of IgE Tc
Figure 14.2
Mast cell degranulation mediated by antigen-crosslinking of IgE bound to IgE Fc
receptors (FceRI).
Figure 14.3
Alternate
ways in which
mast cells can
be induced to
undergo
degranulation.
Figure 14.4
Mediators released during activation of mast cells.
Effector Phase
• Principal clinical features
– Swelling lips, tongue & larynx blocks respiration
– Broncho-constriction prevent expiration
– Dilation of blood vessels causes drop of blood
pressure
– Contraction of intestinal smooth muscles result
in cramps & diarrhea
– Increased vascular permeability causes urticaria
Figure 14.5
A diagrammatic
representation of
late-phase reaction
of type I IgEmediated
hypersensitivity
with some of the
mediators involved.
Figure 14.6
Overview of induction and effector mechanisms in type I hypersensitivity.
Figure 14.7
A diagrammatic representation of the destruction of a worm by eosinophils that
have migrated to the area and been activated following IgE- and antigenmediated mast cell degranulation.
Figure 14.8
Electron micrograph (X6,000) of eosinophils (E) adhering to an antibody- coated
schistosomulum (S). The cell on the left has not yet degranulated, but the one on
the right has discharged electron-dense material (arrows), which can be seen
between the cell and the worm. [Photograph courtesy of Dr. J. Caulfield, Harvard
Medical School.]
Immunologic intervention
• Hyposensitization
– attempts to ‘desensitize’ with repeated low doses of
allergens
– Mode unclear :
• Induction of ‘blocking’ Ab (IgG, IgA?)
• Induction of tolerance due to switch from TH2 to TH1
or induction of Ts
• Clinically altered allergens (allergoids)
Hyposensitization treatment of type I allergy