A 3-year-old boy experiences recurrent sinusitis and an episode of severe pneumonia. As part of his evaluation, Candida extract is injected intradermally. Forty-eight hours later, he returns to the clinic with a firm nodule measuring 16 mm in diameter where the extract was injected. Which of the following cell types is most likely responsible for the reaction observed in this patient?
This patient with recurrent infection is undergoing a delayed-type hypersensitivity skin test to screen for cellular immunodeficiency. This procedure involves intradermal injection of an antigen to which the patient has already been exposed (ie, Candida extract). Development of an area of induration (ie, tissue firmness) surrounding the injection site indicates a positive response and demonstrates effective cellular immunity. Skin testing can also be used as a control in patients with suspected tuberculosis exposure to ensure that the lack of response is not caused by anergy.
Contact dermatitis, granulomatous inflammation, and reactive skin testing (eg, tuberculin skin test, Candida extract skin reaction) are all examples of type IV (delayed type) hypersensitivity reactions. When reexposed to an antigen, previously sensitized T lymphocytes proliferate and release inflammatory cytokines that promote cell-mediated cytotoxicity (CD8+ T cells) and/or macrophage recruitment and activation. The resulting tissue damage and swelling is typically evident 24-48 hours after exposure.
(Choice A) Antibody production by activated B lymphocytes (eg, plasma cells) plays a central role in type I, II, and III hypersensitivity reactions. The timeframe of these reactions can be immediate (type I: eg, anaphylaxis, allergies) or variable (types II and III: eg, most autoimmune disorders, serum sickness).
(Choice B) Eosinophils are phagocytic cells that play a role in the defense against parasitic organisms. These cells are present in small numbers in the bloodstream but are often found in increased numbers in the affected tissues of patients with type I hypersensitivity responses (eg, asthma, allergies).
(Choice C) Mast cells are granulocytes that are the primary mediators of type I (immediate) hypersensitivity reactions (eg, allergies). Sensitized mast cells degranulate and release inflammatory mediators (eg, histamine, prostaglandins) when allergen-specific IgE cross-link on the mast cell Fc receptors, causing rapid swelling and tissue damage.
(Choice D) Neutrophils are the primary phagocytes of the innate immune system and play an ancillary role in some hypersensitivity reactions. Neutrophil deficiency or dysfunction can lead to severe infections without evidence of a significant immune response (eg, pus, infiltrates, erythema).
Educational objective:
Type IV (delayed) hypersensitivity reactions (eg, Candida extract skin test, contact dermatitis) are characterized by erythema and induration that develops 24-48 hours after repeat exposure to an antigen. T lymphocytes mediate the inflammation in these reactions through cytokine release, CD8+ cytotoxicity, and macrophage recruitment.