Page 127 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster

Hypersensitivity Reactions: Mechanisms of Immune-Mediated Injury 113

Table 4–2 Summary of the Action of Mast Cell Mediators in exposure. Systemic exposure to protein antigens (e.g., in
Immediate (Type I) Hypersensitivity bee venom) or drugs (e.g., penicillin) may result in sys-
temic anaphylaxis. Within minutes of the exposure in a
Action Mediators sensitized host, itching, urticaria (hives), and skin ery-
thema appear, followed in short order by profound respira-
Vasodilation, increased Histamine tory difficulty caused by pulmonary bronchoconstriction
vascular permeability PAF and accentuated by hypersecretion of mucus. Laryngeal
Leukotrienes C4, D4, E4 edema may exacerbate matters by causing upper airway
Smooth muscle spasm Neutral proteases that activate obstruction. In addition, the musculature of the entire gas-
trointestinal tract may be affected, with resultant vomiting,
complement and kinins abdominal cramps, and diarrhea. Without immediate
Prostaglandin D2 intervention, there may be systemic vasodilation with a fall
Leukotrienes C4, D4, E4 in blood pressure (anaphylactic shock), and the patient
Histamine may progress to circulatory collapse and death within
Prostaglandins minutes.
PAF
Local reactions generally occur when the antigen is con-
Cellular infiltration Cytokines (e.g., chemokines, TNF) fined to a particular site, such as skin (contact, causing
Leukotriene B4 urticaria), gastrointestinal tract (ingestion, causing diar-
Eosinophil and neutrophil chemotactic rhea), or lung (inhalation, causing bronchoconstriction).
The common forms of skin and food allergies, hay fever,
factors (not defined biochemically) and certain forms of asthma are examples of localized aller-
gic reactions. However, ingestion or inhalation of allergens
PAF, platelet-activating factor; TNF, tumor necrosis factor. also can trigger systemic reactions.

and other chemokines released from TNF-activated epithe- Susceptibility to localized type I reactions has a strong
lium and are important effectors of tissue injury in the genetic component, and the term atopy is used to imply
late-phase response. Eosinophils produce major basic familial predisposition to such localized reactions. Patients
protein and eosinophil cationic protein, which are toxic to who suffer from nasobronchial allergy (including hay fever
epithelial cells, and LTC4 and platelet-activating factor, and some forms of asthma) often have a family history of
which promote inflammation. TH2 cells produce cytokines similar conditions. Genes that are implicated in susceptibil-
that have multiple actions, as described earlier. These ity to asthma and other atopic disorders include those
recruited leukocytes can amplify and sustain the inflamma- encoding HLA molecules (which may confer immune
tory response even in the absence of continuous allergen responsiveness to particular allergens), cytokines (which
exposure. In addition, inflammatory leukocytes are respon- may control TH2 responses), a component of the FcεRI, and
sible for much of the epithelial cell injury in immediate ADAM33, a metalloproteinase that may be involved in
hypersensitivity. Because inflammation is a major compo- tissue remodeling in the airways.
nent of many allergic diseases, notably asthma and atopic
dermatitis, therapy usually includes anti-inflammatory The reactions of immediate hypersensitivity clearly did
drugs such as corticosteroids. not evolve solely to cause human discomfort and disease.
The immune response dependent on TH2 cells and IgE—in
Clinical and Pathologic Manifestations particular, the late-phase inflammatory reaction—plays an
important protective role in combating parasitic infections.
An immediate hypersensitivity reaction may occur as a
systemic disorder or as a local reaction. The nature of the
reaction is often determined by the route of antigen

Immediate Late-
Allergen phase reaction
exposure
Mast cells

Clinical manifestations Edema Vascular Eosinophils
congestion

B C

0 1 4 8 12 16 20

A Hours after allergen exposure

Figure 4–9 Immediate hypersensitivity. A, Kinetics of the immediate and late-phase reactions. The immediate vascular and smooth muscle reaction
to allergen develops within minutes after challenge (allergen exposure in a previously sensitized person), and the late-phase reaction develops 2 to 24
hours later. B–C, Morphology: The immediate reaction (B) is characterized by vasodilation, congestion, and edema, and the late-phase reaction
(C) is characterized by an inflammatory infiltrate rich in eosinophils, neutrophils, and T cells.

(B and C, Courtesy of Dr. Daniel Friend, Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts.)