Mediated Delayed-Type Reactions

The pathophysiologic mechanism of localized cell-mediated allergic reactions is to some extent at least clarified. Penetration or injection of antigen into the tissues (e.g., skin) of a sensitized individual leads to an uptake of antigen by macro- 

When antigen is distributed systemically, and not only locally, for example following ingestion or intravenous injection, a generalized cell-mediated allergic reac- 

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IV. Requirements for Allergens Eliciting Cell-Mediated (Delayed-Type) Allergic Reactions... 

In the present report, we describe the genetic constmcdon, expression, and cell receptor targeted toxicity of a fusion protein composed of the first 485 amino acids of diphtheria toxin linked to amino acids 2 through 133 of IL-2. The fusion protein, IL-2-toxin, is shown to be selectively toxic toward high affinity IL-2 receptor bearing cells in vitro, and to block an activated T-ceU mediated delayed type hypersensitivity (DTH) reaction in vivo. 

Delayed type hypersensitivty (DTH) reactions (synonym type IV allergic reactions) are exaggerated, T-lymphocyte mediated, cellular immune reactions to foreign substances, which require one to two days to manifest clinical symptoms. 

Cell-mediated immunity (CMI) is the result of the activity of many leukocyte actions, reactions, and interactions that range from simple to complex. This type of immunity is dependent on the actions of the T lymphocytes, which are responsible for a delayed type of immune response The T lymphocyte becomes sensitized... 

Type IV reactions are mediated by T cells themselves. Delayed-type hypersensitivity reactions from positive tuberculin tests to contact dermatitis are typical type IV reactions, but understanding T-cell function allows us to further define this category, as shown in Table 51-1. 

Type IV Delayed-type Hypersensitivity (DTH). Delayed-type hypersensitivity reactions are T-cell mediated with no involvement of antibodies. However, these reactions are controlled through accessory cells, suppressor T cells, and monokine-secreting macrophages, which regulate the proliferation and differentiation of T cells. The most frequent form of DTH manifests itself as contact dermatitis. The drug or metabolite binds to a protein in the skin or the Langerhans cell membrane... 

Individualistic adverse reactions to foods can occur through several different types of mechanisms (Taylor and Hefle, 2001). True allergic reactions can include both IgE-mediated immediate hypersensitivity reactions and cell-mediated delayed h)q5ersensitivity reactions (Taylor and Hefle, 2001). However, only IgE-mediafed reactions have been documented to occur with ingestion of molluscan shellfish in sensifive individuals. 

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. 

Type IV Reactions Also termed delay-type hypersensitivity reaction, these take 48-72 h to develop and are not antibody-mediated. Antigens are recognized by CD4+ and/or CD8+ cells in the context of MHC class restrictions on APCs. These reactions are T-cell-mediated where activated T cells release cytokines, resulting in the development of granulomas from macrophages. These mechanisms are responsible for symptoms that may include transplant rejection, contact dermatitis, leprosy, tuberculosis and sarcoidosis. 

Rat (Sprague- Dawley) once (GO) 10 M (altered cell-mediated immunity judged by an increased delayed-type hypersensitivity reaction) Fan etal. 1996... 

A delayed, type IV-mediated reaction These reactions are mediated mainly by T cells. They typically affect the gastrointestinal tract or skin, for example, exacerbation of eczema in children after milk ingestion. 

There are two main sensitization reactions-immedi-ate and delayed hypersensitivity. Immediate type hypersensitivity is the result of antibody-allergen interaction occurring in the skin the reaction that develops is known as allergic contact urticaria. Delayed type hypersensitivity is the result of cell-mediated immunity and is the most frequently reported side effect of topical drugs. Both epidermal and dermal cells play pivotal roles in irritation and sensitization. Keratinocytes... 

IgE and/or specifically reactive lymphocytes do not mediate many of the adverse reactions to cromoglicate, which mimic allergic processes of the immediate or delayed type. These reactions fulfilled the criteria that characterize pseudo-allergic reactions (3,10). There is a much higher incidence of such adverse reactions when cromoglicate is used orally in the treatment of food allergy, as high as 29% of cases treated (3,10). 

However, there are times when the immune system acts in an exaggerated manner leading to tissue damage. This is referred to as hypersensitivity. In the classic Coombs and Cell classification system, there are four types of hypersensitivity reactions. The first three (types 1-3) are mediated by antibody (e.g., IgG, IgE). The fourth type (type 4) is mediated by antigen-specific T cells and is also known broadly as delayed-type hypersensitivity (DTH). It is delayed because the reaction appears hours to days after antigen crosses into the skin. Though often thought of as... 

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