Delayed-type hypersensitivity reactions

Type IVb Reactions Delayed Type Hypersensitivity Reactions... 

Friedbender, M.H. and Dvorak, H.F. (1977). Morphology of delayed type hypersensitivity reactions in the guinea pig cornea. J. Immunol. 118, 1558-1566. 

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. 

Biedermann, T. et al, Reversal of established delayed type hypersensitivity reactions following therapy with IL-4 or antigen-specific Th2 cells. Eur. J. Immunol., 31, 1582, 2001. 

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... 

Type IV Hypersensitivity. There are several well-established preclinical models for assessing Type IV (delayed-type) hypersensitivity reactions following dermal exposure, but not for predicting this response after systemic exposure. 

In vivo effects of interleukin-10 on contact hypersensitivity and delayed-type hypersensitivity reactions. J Invest Dermatol 1994 103 211-216. 

Several immune-regulated models have been described, of which the delayed-type hypersensitivity reaction in the skin is an example. In several species application of allergic or con-tact-sensitizing substances results in a local inflammatory reaction involving adhesion mole-... 

Acute dermal application of dilute or full-strength DCP rapidly produced erythema and edema in rats, rabbits, and guinea pigs. Delayed-type hypersensitivity reactions and contact sensitization have also been reported in guinea pigs and humans. ... 

Roychowdhury, S. and Svensson, C.K. (2005) Mechanisms of drug-induced delayed-type hypersensitivity reactions in the skin. AAPS Journal,... 

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. 

Fibrosis resulting in the loss of normal organ structures is the hallmark of chronic rejection. The fibrosis may be due to wound healing, which is then followed by the cellular necrosis of acute rejection. However, it must be pointed out that chronic rejection develops many times in the absence of acute rejection. Fibrosis may be a result of several diverse factors such as equation of chronic rejection with chronic delayed-type hypersensitivity reaction, injury to blood vessels and resulting response to chronic ischemia, the proliferation of smooth muscle cells in the intima of arterial walls producing vascular occlusion, or persistent viral infections that will induce cellular immune response. 

In a second study of intermediate duration (6 weeks), weanling rats were fed dietary levels of 0, 20, and 80 mg/kg/day bis(tributyltin)oxide (Krajnc et al. 1984). The expected decreased organ weights and lymphocytopenia were seen. Suppression of thymus-dependent immunity was produced as shown by depressed delayed-type hypersensitivity reactions and reduced response of the thymus and spleen cells to T-cell mitogens due to reduced numbers of T-cells. Natural killer activity was decreased in the spleen. This observation was confirmed by Van Loveren et al. (1990). This was particularly true at the 80 mg/kg/day level. The effects produced by bis(tributyltin)oxide appear to be due to direct action of the compound on the lymphocytes in the thymus since cell damage was seen. 

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

Nuhoglu, Y., Nuhoglu, C., and Ozcay, S. 2003. The association between delayed type hypersensitivity reaction to Mycobacterium tuberculosis and atopy in asthmatic children. Allergol Immunopathol (Madr) 31(1) 14—17. 

Pichler B, Kneilling M, Haubner R, Braumuller H, Schwaiger M, Rocken M, et al. Imaging of delayed-type hypersensitivity reaction by PET and 18F-galacto-RGD. J Nucl Med 2005 46 184—189. 

Erythematous nodules or infiltrated and sometimes eczema-hke plaques at the site of injection are common adverse effects of subcutaneous standard heparin 3-21 days after starting heparin treatment. They are probably delayed-type hypersensitivity reactions and are also seen with low molecular weight heparin (65-69). There can be cross-reactivity between standard heparin and low molecular weight heparin (69). 

Schmidt P, Boehncke WH. Delayed-type hypersensitivity reaction to kava-kava extract. Contact Dermatitis 2000 42(6) 363. ... 

Rodriguez-Pena R, Lopez S, Mayorga C, AntunezC, Fernandez TD, Torres MJ, Blanca M Potential Involvement of dendritic cells in delayed-type hypersensitivity reactions to beta-lactams. J Allergy Clin Immunol 2006 118 949-56. 

Cetyl alcohol has been associated with allergic delayed-type hypersensitivity reactions in patients with stasis dermatitis. Cross-sensitization with cetostearyl alcohol, lanolin, and stearyl alcohol has also been reported. It has been suggested that hypersensitivity may be caused by impurities in commercial grades of cetyl alcohol since highly refined cetyl alcohol (99.5%) has not been associated with hypersensitivity reac-... 

Measles Infection. In a historical cohort study in Guinea-Bissau, measles infection was associated with a large reduction in the risk of skin test positivity to house dust mites, compared with children who had been vaccinated against measles and not acquired the infection [ 102(111C)]. The mechanism of this effect is difficult to fit into the hygiene hypothesis because measles causes sequential Thl and Th2 cytokine responses. Measles vaccination leads to an enhanced Th2-like effect, with suppression of delayed-type hypersensitivity reactions [159(NC)]. 

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