The ability of CD4 T cells to mediate contact hypersensitivity responses is established by experimental exposure to the strong sensitizing chemical picryl chloride. Picryl chloride modifies extracellular self proteins by haptenation. These haptenated proteins can then be proteolytically processed by APCs, yielding haptenated peptides that bind to self-MHC class II molecules and are recognized by TH1 cells. When sensitized TH1 cells recognize these complexes, they produce extensive inflammation by activating macrophages (see Fig. 14.22). Common clinical features of allergic contact hypersensitivity responses are erythema of the affected skin; development of a dermal and epidermal infiltrate consisting of monocytes, macrophages, lymphocytes, scant neutrophils, and mast cells; formation of intraepidermal abscesses; and vesicles (blisterlike collections of edema fluid between the dermis and epidermis).
Some insect proteins also elicit a delayed-type hypersensitivity response. One example of this in the skin is a severe reaction to mosquito bites. Instead of a small itchy bump, people allergic to proteins in mosquito saliva can develop an immediate hypersensitivity reaction such as urticaria and swelling or, much more rarely, anaphylactic shock (see Section 14-10). Some allergic individuals subsequently develop a delayed reaction (consisting of a late-phase response) that can include profound swelling that can involve an entire limb.
Contact hypersensitivity responses to divalent cations such as nickel have also been observed. These divalent cations can alter the conformation or the peptide binding of MHC class II molecules, and thus provoke a T-cell response. In humans, nickel can also bind to the receptor TLR-4 and produce a pro-inflammatory signal. Sensitization to nickel is widespread as a result of prolonged contact with nickel-containing items such as jewelry, buttons, and clothing fasteners, but some countries now have standards that specify that such products must have non-nickel coatings, and this is reducing the prevalence of nickel allergy in those countries.
Finally, although this section has focused on the role of TH1 and cytotoxic T cells in inducing cellular hypersensitivity reactions, there is evidence that antibody and complement might also have a role. Mice deficient in B cells, antibody, or complement show impaired contact hypersensitivity reactions. In particular, IgM antibodies (produced in part by B1 cells), which activate the complement cascade, facilitate the initiation of these reactions.
Fig. 14.23 Blistering skin lesions on the hand of a patient with allergic contact dermatitis caused by poison ivy.
Photograph courtesy of R. Geha.
Fig. 14.24 The pathological features of celiac disease. Left: the surface of the normal small intestine is folded into fingerlike villi, which provide an extensive surface for nutrient absorption. Right: the local immune response against the food protein α-gliadin, a prominent component of wheat, oat, and barley gluten, leads to massive infiltration of the lamina propria (in the deeper, inner portion of the villi) with CD4 T cells, plasma cells, macrophages, and smaller numbers of other leukocytes, ultimately leading to destruction of the villi. In parallel, there is lengthening and increased mitotic activity in the underlying crypts, where new epithelial cells are produced. Because the villi contain all the mature epithelial cells that digest and absorb foodstuffs, their loss can result in life-threatening malabsorption and diarrhea. Photographs courtesy of Allan Mowat.
14-17 Celiac disease has features of both an allergic response and autoimmunity.