Insulitis (chronic inflammation in islets), destruction of β cells; diabetes
Chronic intestinal inflammation, obstruction
Epidermal necrosis, dermal inflammation, causing skin rash and blisters
Examples of human T cell–mediated diseases are listed. In many cases, the specificity of the T cells and the mechanisms of tissue injury are inferred based on the similarity with experimental animal models of the diseases.
Activated TH17 cells secrete cytokines that recruit neutrophils and monocytes.
The classic example of DTH is the tuberculin reaction (known in clinical medicine as the PPD skin test), which is produced by the intracutaneous injection of purified protein derivative (PPD, also called tuberculin), a protein-containing antigen of the Mycobacterium tuberculosis bacillus. In a previously exposed individual, reddening and induration of the site appear in 8 to 12 hours, reach a peak in 24 to 72 hours, and thereafter slowly subside. Morphologically, delayed-type hypersensitivity is characterized by the tion and inflammation. Drug reactions often manifest as skin rashes.
CD4+ T cell–mediated inflammation is the basis of tissue injury in many organ-specific and systemic autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis, as well as diseases probably caused by uncontrolled reactions to bacterial commensals, such as inflammatory bowel disease (see
Table 5.6
Fig. 5.17 Delayed hypersensitivity reaction in the skin. (A) Perivascular accumulation (“cuffing”) of mononuclear inflammatory cells (lymphocytes and macrophages), with associated dermal edema and fibrin deposition. (B) Immunoperoxidase staining reveals a predominantly perivascular cellular infiltrate that marks positively with anti-CD4 antibodies. (Courtesy of Dr. Louis Picker, Department of Pathology, Oregon Health Sciences University, Portland, Oregon.) accumulation of mononuclear cells, mainly CD4+ T cells and macrophages, around venules, producing perivascular “cuffing” (
Fig. 5.17
Prolonged DTH reactions against persistent microbes or other stimuli may result in a special pattern of reaction called granulomatous inflammation. The initial perivascular CD4+ T cell infiltrate is progressively replaced by macrophages over a period of 2 to 3 weeks. These accumulated macrophages typically exhibit morphologic evidence of activation; that is, they become large, flat, and eosinophilic, and are called epithelioid cells. The epithelioid cells occasionally fuse under the influence of cytokines (e.g., IFN-γ) to form multinucleate giant cells. An aggregate of epithelioid cells, typically surrounded by a collar of lymphocytes, is called a granuloma (
Fig. 5.18A ). The process is essentially a chronic form of TH1-mediated inflammation and macrophage activation (see
Fig. 5.18B ). Older granulomas develop an enclosing rim of fibroblasts and connective tissue. In certain situations, such as infection by helminths known as schistosomes, TH2 cells also are involved, and as a result eosinophils are prominent in the lesions. Recognition of granulomas is of diagnostic importance because they are seen only in a limited number of conditions (Chapter 3).