Porth's Essentials of Pathophysiology, 4e

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Infection and Immunity

U N I T 4

Antigen

CD4

2

T H

IL-4

B cell

IgE-secreting plasma cell

IL-3, IL-5

Antibody

Basophil

Eosinophil recruitment

Mast cell

Sensitization of mast cell or basophil

FIGURE 16-1. Type I, IgE-mediated hypersensitivity reaction.The stimulation of B-cell differentiation by an antigen-stimulated type 2 helperT (T H 2) cell leads to plasma cell production of IgE and mast cell or basophil sensitization. Subsequent binding of the antigen produces degranulation of the sensitized mast cell or basophil with release of preformed mediators that leads to a primary, or early-phase, response.T H 2T-cell recruitment of eosinophils, along with the release of cytokines and membrane phospholipids from the mast cell, leads to a secondary, or late-phase, response. IgE, immunoglobulin E; IL, interleukin.

Release of cytokines

Recruitment and activation of inflammatory cells

Degranulation and release of mediators

Membrane phospholipids Arachidonic acid Prostaglandins Leukotrienes

Primary early response Vasodilation Vascular damage Smooth muscle spasm

Secondary late response

Mucosal edema Mucus secretion Leukocyte infiltration Epithelial damage Bronchospasm

(see Chapter 3). The leukotrienes and prostaglandins produce responses similar to histamine, although their effects are delayed and prolonged by comparison. Mast cells also produce cytokines and chemotactic factors that prompt the influx of eosinophils and leukocytes to the site of allergen contact, additionally contributing to the inflammatory response. At this point, it is important to note that not all IgE-mediated responses produce discomfort and dis- ease. Type I hypersensitivity, particularly the late- phase response, plays a protective role in the control of parasitic intestinal infections. IgE antibodies directly damage the larvae of these parasites by recruit- ing inflammatory cells and causing antibody-depen- dent cell-mediated cytotoxicity. This type of type I

hypersensitivity reaction is particularly important in developing countries where much of the population is infected with intestinal parasites. Systemic (Anaphylactic) Reactions Anaphylaxis is a systemic life-threatening hypersen- sitivity reaction characterized by widespread edema, difficulty breathing, and vascular shock secondary to vasodilation 2,6–8 (see section on anaphylactic shock, Chapter 20). It results from the presence of antigen introduced by injection, insect sting, or absorption across the epithelial surface of the skin or gastroin- testinal mucosa. The level of severity depends on the level of sensitization. Even small amounts of antigen,