Synonyms and Key Differences
Type IV hypersensitivity reactions are known in medical literature by several equivalent terms, each reflecting a certain aspect of the pathological process. The term delayed-type hypersensitivity (DTH) is most frequently used. Additionally, this type of reaction is referred to as cell-mediated, infectious-allergic, and tuberculin-type.
A fundamental, key difference between type IV reactions and all other types of allergies is the complete absence of any role for antibodies (Abs) in their development mechanism. The main and only effectors here are specific T cells. They are responsible for recognizing the foreign agent and triggering the subsequent cascade of tissue damage.
Initiation and Cellular Mechanism
The development of delayed-type hypersensitivity represents a strict sequence of cellular interactions. The process begins when a foreign antigen (Ag) enters the body and is captured by specialized structures.
- Sensitization. The first step in the implementation mechanism is the interaction of T cells with the foreign antigen. This process does not occur directly—it requires the obligatory participation of antigen-presenting cells. These cells process and "present" the antigen to T lymphocytes. As a result of this contact, sensitized T cells capable of active response are formed.
- Macrophage recruitment. In the second stage, macrophages are actively recruited into the developing inflammatory focus.
- Destruction. The cooperative work of various T lymphocytes (predominantly cytotoxic T cells) and phagocytes aims to detect the foreign antigen. Once successfully detected, these cells destroy not only the antigen itself but also its carrier, which can be either an entire cell or a non-cellular structure.
Mechanisms of Tissue Damage
Pathological effects on tissues in Type IV hypersensitivity reactions are realized through two main pathways, in which sensitized T lymphocytes play the leading role.
- Direct cytotoxic effect. Sensitized T lymphocytes (primarily cytotoxic T cells) come into direct contact with target cells bearing the foreign antigen and exert a direct destructive effect on them.
- Mediated effect. In addition to direct destruction, T cells release specific biologically active substances—lymphokines. Through these mediators, an indirect damaging effect on surrounding tissues is realized, amplifying the inflammatory response and attracting fresh waves of effector cells to the lesion.
Pathophysiological Changes at the Tissue Level
The development of DTH is accompanied by pronounced pathophysiological changes in tissues. The main processes include alteration, a specific inflammatory response, and severe microcirculatory disorders.
Alteration in Type IV reactions has a pronounced destructive character. Large-scale destruction and subsequent elimination (removal) occur not only for damaged cells, but also for completely unaffected cells and non-cellular elements of the body's own tissues.
Simultaneously, severe microcirculatory disorders develop. Hemocirculation (blood flow) and lymph circulation disturbances arise in the lesion. These vascular failures inevitably lead to capillaro-trophic insufficiency—a state where tissues stop receiving adequate nutrition. The natural outcome of such insufficiency is profound dystrophy and subsequent necrosis (death) of the affected tissue.
Granulomatous Inflammation
The most typical and characteristic morphological manifestation of Type IV hypersensitivity reactions is granulomatous inflammation. In response to the presence of an antigen in tissues, the active formation of specific nodules—granulomas—begins.
, The composition of such an allergic granuloma is highly specific and reflects the cellular nature of the immune response. Initially, lymphocytes and mononuclear phagocytes accumulate in the lesion. Later, these phagocytes undergo a complex morphological transformation: they turn into epithelioid cells and fuse to form giant cells. Additionally, fibroblasts participate in tissue organization within the forming granuloma.
Classic clinical examples of reactions proceeding with the formation of such granulomas and the development of DTH are diagnostic tests—the tuberculin and brucellin tests.