Antibodiesandimmunecomplexesmaydepositintissuesorbloodvessels,andelicitanacuteinflammatoryreactionbyactivatingcomplement,withreleaseofbreakdownproducts,orbyengagingFcreceptorsofleukocytes.Theinflammatoryreactioncausestissueinjury.
Antibodiescanbindtocellsurfacereceptorsorotheressentialmoleculesandcausefunctionalderangements(eitherinhibitionorunregulatedactivation)withoutcellinjury.
Several autoimmune disorders, as well as pathologic reactions to environmental chemicals and persistent microbes, are now known to be caused by T cells ( 5.6 ). Two types of T cell reactions are capable of causing tissue injury and disease: (1) cytokine-mediated inflammation, in which the cytokines are produced mainly by CD4+ T cells, and (2) direct cell cytotoxicity, mediated by CD8+ T cells (
Fig. 5.16 ). This group of diseases is of great clinical interest because T cells are increasingly recognized as the basis of chronic inflammatory diseases, and many of the new rationally designed therapies for these diseases have been developed to target the abnormal T cell reactions.
In CD4+ T cell–mediated hypersensitivity reactions, cytokines produced by the T cells induce inflammation that may be chronic and destructive. The prototype of T cell–mediated inflammation is delayed-type hypersensitivity (DTH), a tissue reaction to antigens given to immune individuals. In this reaction, an antigen administered into the skin of a previously immunized individual results in a detectable cutaneous reaction within 24 to 48 hours (hence the term delayed, in contrast to immediate hypersensitivity).
As described earlier, naïve T cells are activated in secondary lymphoid organs by recognition of peptide antigens displayed by dendritic cells. The T cells differentiate into effector cells under the influence of various cytokines (see
Figs. 5.9 5.10 ). Classical T cell–mediated hypersensitivity is a reaction of TH1 effector cells, but TH17 cells also may contribute to the reaction, especially when neutrophils are prominent in the inflammatory infiltrate. TH1 cells secrete cytokines, mainly IFN-γ, which are responsible for many of the manifestations of delayed-type hypersensitivity. IFNγ-activated (classically activated) macrophages produce substances that destroy microbes and damage tissues, and mediators that promote inflammation (Chapter 3).
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Hypersensitivity: Immunologically Mediated Tissue Injury143
Table 5.6 T Cell–Mediated Diseases
Specificity of Pathogenic T Cells
Collagen?Citrullinated self proteins?
Protein antigens in myelin (e.g., myelin basic protein)
Antigens of pancreatic islet β cells (insulin, glutamic acid decarboxylase, others)
Enteric bacteria; self antigens?
Various environmental chemicals (e.g., urushiol from poison ivy or poison oak, therapeutic drugs)
Principal Mechanisms of Tissue Injury
Inflammation mediated by TH17 (and TH1?) cytokines; role of antibodies and immune complexes?
Inflammation mediated by TH1 and TH17 cytokines, myelin destruction by activated macrophages
T cell–mediated inflammation, destruction of islet cells by CTLs
Inflammation mediated by TH1 (and TH17?) cytokines
Chronic arthritis with inflammation, destruction of articular cartilage