Causes of Delayed Cell-Mediated Reactions

Type IV (Delayed Cell-Mediated) Reactions

Type III (Immune Complex) Reactions

Type III reactions involve antibodies against soluble antigens circulating in the serum. (In contrast, type II immune reactions are directed against antigens located on cell or tissue surfaces.) Immune complexes form only when certain ratios of antigen and antibody occur. The antibodies involved are usually IgG. A significant excess of antibody leads to the formation of complement-fixing complexes that are rapidly removed from the body by phagocytosis. When there is a significant excess of antigen, soluble complexes form that do not fix complement and do not cause inflammation. However, when a certain antigen-antibody ratio exists, usually with a slight excess of antigen, the soluble complexes that form are small and escape phagocytosis.

Figure 4 illustrates the consequences. These complexes circulate in the blood, pass between endothelial cells of the blood vessels, and become trapped in the basement membrane beneath the cells. In this location, they may activate complement and cause a transient inflammatory reaction: attracting neutrophils that release enzymes. Repeated introduction of the same antigen can lead to more serious inflammatory reactions, causing damage to the basement membrane's endothelial cells within 2 to 8 hours.

Type IV reactions involve cell-mediated immune responses and are caused mainly by T cells. Instead of occurring within a few minutes or hours after a sensitized individual is again exposed to an antigen, these delayed cell-mediated reactions, (or delayed hypersensitivity) are not apparent for a day or more. A major factor in the delay is the time required for the participating T cells and macrophages to migrate to and accumulate near the foreign antigens. Transplant rejection is most commonly mediated by cytotoxic T lymphocytes, but other mechanisms are by antibody-dependent cell-mediated cytotoxicity or complement-mediated lysis.

Sensitization for delayed hypersensitivity reactions occurs when certain foreign antigens, particularly those that bind to tissue cells, are phagocytized by macrophages and then presented to receptors on the T-cell surface. Contact between the antigenic determinant sites and the appropriate T cell causes the T cell to proliferate into mature differentiated T cells and memory cells.

When a person sensitized in this way is reexposed to the same antigen, a delayed hypersensitivity reaction might result. Memory cells from the initial exposure activate T cells, which release destructive cytokines in their interaction with the target antigen. In addition, some cytokines contribute to the inflammatory reaction to the foreign antigen by attracting macrophages to the site and activating them.

Дата добавления: 2015-06-04