Allergy and Hypersensitivity. I. Introduction. A. Definitions. Allergy Immune-mediated response to innocuous environmental antigen Can be humoral or cell-mediated reaction Usually involves prior exposure to antigen resulting in sensitization of individual Allergen Innocuous antigen
Allergy and Hypersensitivity
II. Type I (Anaphylaxis) Hypersensitivity
High affinity FceRI is functional
on mast cells, basophils, and
activated eosinophils. It is
composed of a,b and two g
chains. Crosslinking of FceRI
on cells by Ag and IgE induces
Fig. 10.24: Allergen-induced release of histamine by mast cells in skin
causes localized swelling. Swellings (wheals) appear 20 min. after
intradermal injection of ragweed pollen (R), histamine (H). Saline bleb (S) is due to volume of fluid.
Properties of inhaled
allergens that favor TH2
priming that promotes
IgE isotype switching.
Sensitization to an inhaled allergen.
Soluble allergen is processed by APC and displayed to TH2 T cells.
T cells help B cells to produce IgE which then binds to mast cells. IL-4 promotes isotype switching to IgE.
Fig. 10.21: Allergic rhinitis (hay fever) is caused by inhaled allergen entering the respiratory tract. Sneezing, runny nose – nasal discharge is full of eosinophils. Allergic conjunctivitis results if the conjunctiva of the eye is affected (itchy, watery, and swelling of eyes).
Fig. 10.25: Ingested allergen can cause vomiting, diarrhea and urticaria.
Summary of Type I Hypersensitivity Reactions
Mast cell stained for protease
abundant granules residing
in the cytoplasm.
Fig. 10.5: Mast cell products involved in allergic reactions.
by different enzyme pathways starting with arachidonic
Fig. 10.8: Eosinophils display a unique staining pattern with bilobed
nuclei and stain pink with eosin.
Eosinophils are specialized granulocytes that release toxic mediators
in IgE-mediated responses.
Fig 10.16: Immediate and late-phase reactions to house dust mite
allergen (HDM) injected intradermally. Saline injection = control.
Wheal = raised area of skin around injection site; flare = redness
(erythema) spreading out from the wheal.
Fig. 10.23: Inflammation of the airways in chronic asthma restrict breathing
A = section through bronchus of individual who died from asthma.
MP = mucus plug – restricts airway. White plug depicts remaining passageway in bronchial lumen.
B = Bronchial wall at higher magnification demonstrating presence of inflammatory infiltrate consisting of eosinophils, neutrophils, and lymphocytes. L = lumen of bronchus.
Figure 10.20: Effect of epinephrine on blood pressure
Time 0 = point at which anaphylactic response began.
Arrows = times when epinephrine was administered.
III. Type II (Cytotoxic) Hypersensitivity
Hemolytic Disease of the
Type II hypersensitivity
from Rh incompatibilities
between mother and father
Spacing of Rh antigen is
too far to activate C’ or
Fetal RBC destroyed by macro-
phages causing edema.
This may in turn lead to heart
failure, edema and fetal death
Penicillin may also bind to surface proteins
on human cells (RBC = most common).
This creates a new epitope that can act
like a foreign Ag.
Penicillin interferes with the
bacterial enzyme transpeptidase
after binding to the active site in
Fig. 10.27: Penicillin-protein conjugates stimulate the production of
Penicillin-modified RBC get coated with C3b as a bystander effect of C’ activation by bacterial activating surfaces for which the penicillin was administered. This initiates the process by inducing opsonization by macrophages.
IV. Type III (Immune complex) Hypersensitivity
The pathology of type III hypersensitivity reactions is determined by the sites of immune-complex deposition.
Localized deposition of immune complexes within a tissue causes a type III
Serum sickness is a classic example of a transient immune-complex mediated syndrome.
V. Type IV Hypersensitivity
Fig. 10.33: Summary