Hypersensitivity reactions Lymphocyte-mediated

Type IV, or delayed-hypersensitivity, reactions are mediated by sensitized T-lymphocytes and macrophages. When sensitized cells come in contact with antigen, an inflammatory reaction is generated by the production of lymphokines and the subsequent influx of neutrophils and macrophages. 

Type IV allergic reactions are cell-mediated hypersensitivity reactions which are characterized by the expansion of T lymphocytes specific for foreign substances exposed on cell surfaces. In type FVa allergic reactions, this results in the cell-mediated destruction of the cells, whereas in type FVb allergic reactions an... 

These are called delayed hypersensitivity reactions since they normally occur 6-24 hours after exposure. A cell-mediated allergy involves the interaction of food allergens with sensitised lymphocytes, which usually occurs in the gastrointestinal tract. The sensitised lymphocytes produce lymphokines and the generation of cytotoxic T lymphocytes. These latter cells destroy other intestinal cells, including the epithelial cells that are critical for absorption. 

Anti-lymphocyte globulin (ALG) has been prepared as an highly purified solution of y-globulins with antilymphocyte activity by immunizing horses with human lymphocytes. It activates complement-mediated destruction of lymphocytes and thus decreases cellular immunity with only a limited effect on humoral immunity. Anti-lymphocyte globulin suppresses delayed type hypersensitivity reactions. It is used for the prevention and treatment of rejection episodes of transplanted organs. It also has some indication for the management of idiopathic aplastic anemia. Adverse effects include pain at the site of injection, erythema, serum sickness and rarely anaphylactic shock and thrombocytopenia. 

Most anaphylactoid reactions are due to a direct or chemical release of histamine, and other mediators, from mast cells and basophils. Immune-mediated hypersensitivity reactions have been classified as types I-IV. Type I, involving IgE or IgG antibodies, is the main mechanism involved in most anaphylactic or immediate hypersensitivity reactions to anaesthetic drugs. Type II, also known as antibody-dependent hypersensitivity or cytotoxic reactions are, for example, responsible for ABO-incompatible blood transfusion reactions. Type III, immune complex reactions, include classic serum sickness. Type IV, cellular responses mediated by sensitised lymphocytes, may account for as much as 80% of allergic reactions to local anaesthetic. 

The pathophysiology of VKC is derived from a combination of type I and IV hypersensitivity reactions.This allergic response involves IgE,Th-2 lymphocytes, eosinophils, mast cells, basophils, neutrophils, macrophages, proin-flammatory cytokines, interleukins, histamine, and other associated mediators. Also involved in this immune response are hormonal and neuroendocrine influences. This immune response results in the clinical manifestations of photophobia, itching, redness, tearing, papillae, corneal vascularization, mucous discharge, and plaque formation. 

AKC is believed to be a result of both a type I (IgE) and type IV (T cell-mediated) hypersensitivity reaction. Patients with AKC may have a depressed T-cell function. Elevated levels of serum IgE and tear IgE have been found. T lymphocytes and eosinophils are important components of AKC s pathogenesis. See Table 27-2 for immune findings. 

Smdies in the 1970s showed that cyclosporin inhibits humoral immunoreactions, and that it had a selective effect on T-cell dependent immunoreactions and that its effect was reversible. Cyclosporin is considered to interfere with the process for primary T-cell activation. In this way the formation of T-effector cells, cytotoxic T-lymphocytes or killer lymphocytes, which have the dominant function in cell mediated immune reactions like rejecting an allograft in transplantation surgery and delayed hypersensitivity reaction, is prevented. 

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