A 14-year-old boy is brought to the emergency department by his mother after he develops a sudden rash. He was trying to retrieve a baseball that had rolled under a log when he got stung by something. By the time he told his mom, his body was covered in welts. Within minutes, the patient's face started to swell and he was having a hard time swallowing. The patient's blood pressure is 70/50 mm Hg and heart rate is 120/min. Physical examination shows erythematous, raised plaques over the trunk, extremities, and face. Lung auscultation reveals bilateral expiratory wheezes. The mother is not aware of the child having any similar reaction in the past. Which of the following most likely triggered this patient's condition?
Hypersensitivity reactions | |||
Humoral | Cellular | Examples | |
Type I |
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Type II |
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Type III |
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Type IV |
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NK = natural killer; PSGN = poststreptococcal glomerulonephritis. | |||
This patient is experiencing anaphylaxis, a type I (immediate) hypersensitivity reaction that occurs in response to allergen (eg, venom from insect sting) exposure. An allergen is an antigen that promotes a robust immune response only in a subset of the population.
On initial exposure to allergen, a patient who will eventually develop an allergic response will undergo antibody class switching to IgE in B lymphocytes specific for these allergens. Antigen-specific IgE produced by plasma cells binds to IgE receptors on basophils in the blood and mast cells in the tissues. When the relevant antigen (allergen) interacts with cell bound-specific IgE, these antibodies will cross-link, causing degranulation and release of chemical mediators (histamine, prostaglandin, leukotrienes) responsible for systemic vasodilation, increased vascular permeability, bronchoconstriction, and hemodynamic instability.
(Choice A) Antibody-antigen complex deposition in the vasculature occurs with Type III hypersensitivity reactions (eg, serum sickness, Arthus reaction).
(Choice B) Antibody-dependent cell-mediated cytotoxicity occurs in type II hypersensitivity reactions wherein IgM or IgG binds to antigens expressed on the cell surface. These antibodies are then recognized by Fc receptors on immune cells, triggering the release of perforin and granzymes that ultimately leads to cell lysis and death.
(Choice C) CD8+ T lymphocyte-mediated hypersensitivity is a delayed rather than immediate type of immune response. Type IV hypersensitivity is unique in that it is not cell- versus antibody-mediated (seen in types I-III).
(Choice E) Complement-mediated cytotoxicity is a function of circulating IgM and IgG, not IgE. This pathway plays a role in the damage associated with Type II and III hypersensitivity reactions. IgM is the antibody most efficient at initiating the classical complement cascade because it circulates as a pentamer (allows for increased complement interaction).
Educational objective:
Type I hypersensitivity reactions are mediated by the interaction of allergen with preexisting IgE bound to basophils and mast cells. This facilitates cross-linking of the surface IgE molecules that signals the cell to degranulate releasing chemical mediators (eg, histamine, heparin). These agents are responsible for the immediate signs and symptoms of allergy, from a local wheal and flare to life-threatening anaphylaxis.