Type IV hypersensitivity reactions

Figure 6.34 The basis of type IV hypersensitivity reactions. This is cell mediated rather than antibody mediated.

Type IV hypersensitivity reactions. This type of immune response is unlike the other three in that antibodies are not involved, the response being initiated by sensitized ThI cells. 

Allergic eye disease may result from a type I or type IV hypersensitivity reaction. Typically, on initial exposure to the allergen, there are no clinical manifestations. In contrast, clinical manifestations occur in sensitized individuals or... 

Three cases of allergic dermatitis have been described after intravesical mitomycin (23). A type IV hypersensitivity reaction was demonstrated on patch-testing. Six cases of purpuric allergic drug eruption from intravesicular mitomycin have been reported (24). 

Recent studies characterizing the basis for chemically induced hypersensitivity have uncovered an important interplay between type I hypersensitivity reactions, manifested primarily as respiratory sensitization, and type IV hypersensitivity reactions, manifested primarily as contact sensitization. The most important observation came from studies which showed that a predominantly respiratory sensitizer would still trigger an IgE response when applied topically. This observation can be accounted for by the cytokine network model which was described previously as important for cross talk between humoral immunity and cell-mediated immunity. Basically, a chemical with the capability of being a respiratory sensitizer will trigger an IgE response regardless of its route of exposure because it selects or supports the development of a Tni-dependent response, with the associated cytokine profile, IL-4, IL-5, and IL-10. In contrast, a chemical which lacks the capability of being a respiratory sensitizer but which can still trigger contact dermititis, will select or support a THi-dependent response, with the associated cytokine profile, IL-2 and IFN-y. 

Skin testing is based on the application of chemical solutions on the epidermis, with (scratch-patch test) or without (patch test) scarification of the epidermis. The occurrence of a typical type IV hypersensitivity reaction — i.e. erythema, vesiculation, and evidence of cellular infiltrate — 48-96 h after application is typical for a positive reaction. A drawback of this approach is that the metabolism of the chemical, leading to the generation of a reactive metabolite, and the presentation of the chemical to the immune system may be different according to the route of entry. 

Delayed hypersensitivity (Tdh) cells Those T cells (inflammatory ThI) that produce lymphokines in cell-mediated (Type-IV) hypersensitivity reactions. 

Another subdivision of type IV hypersensitivity reactions has categories distinguished by the effector cells and mediators involved together with the resulting associated cutaneous reactions. Four subdivisions are defined type IVa, mediated by monocytes with IFN-y as dominant cytokine type IVb, mediated by eosinophils with IL-5 and IL-4 involvement type IVc, mediated by T cells with perforin and granzyme B as important effector molecules and type IVd, mediated by neutrophils with IL-8 involvement. Representative skin reactions for the so-called types IVa, b, c, and d are, respectively, maculopapular rash, maculopapular rash with eosinophilia, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). 

Type IV hypersensitivity reactions are mediated by antigen-specific effector T cells. Reactions generally occur 48-72 h after antigen exposure and are therefore referred to as delayed reactions. 

The range and diversity of adverse effects provoked by contrast media remain poorly understood and hence difficult to categorize. For the allergist and clinical immunologist used to thinking of immediate reactions as type I allergic responses mediated by IgE antibodies and delayed reactions as type IV hypersensitivity reactions mediated by antigen-specific effector T cells, adverse reactions to contrast media, divided... 

HP is an airway-centered ILD that may be acute or chronic. Acute HP is a type III hypersensitivity reaction, and chronic HP is a type IV hypersensitivity reaction. In both cases, the antigen is introduced to the lung through the airways and results in airway inflammation of some degree (23). Bronchioles may show features of constrictive bronchiolitis with subepithelial granulation tissue and fibrosis however, complete luminal obliteration is not seen. As the disease progresses, peribronchiolar metaplasia develops via the canals of Lambert, also called Lambertosis (24). 

Immunologic Skin testing of 26 patients clinically diagnosed with immediate (type I) hypersensitivity to infliximab found seven positives (30%) and six of these had infliximab-reactive serum IgE antibo es. One skin test-positive patient had no detectable IgE antibodies to the mAb [155 ]. After multiple infusions with infliximab, a 61-year-old woman with Crohn s disease experienced an acute anaphylactic reaction immediately after the start of an infusion. Although anti-infliximab IgE antibodies were not detected, the concentration of anti-infliximab IgG was high and this remained the case 1 year after the mAb was discontinued. Substitution of adalimumab for infliximab 1 week after the anaphylactic reaction was tolerated until the 12th day when the patient displayed a delayed, type IV hypersensitivity reaction mediated by IgG antibodies specific for adalimumab [ISb ]. In addition to types I and IV hypersensitivities to infliximab, other immune-mediated reactions representing the other hypersensitivity states also occur to infliximab. This is illustrated by a recent report of a case of a 27-year-old woman of infliximab-induced systemic lupus erythematosus [157 ], an autoimmune connective tissue disease which is both a type II and a type III hypersensitivity response. 

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... 

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. 

The canse of GPC is mnltifactorial,with mechanical trauma and hypersensitivity reactions involved. In those genetically predisposed, the antigen-coated contact lens may trigger the hypersensitivity reaction, which inclndes both an immediate type 1 reaction and a type IV delayed reaction. 

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. 

A 30-year-old Japanese man with polyarthritis, in whom sodium aurothiomalate for 3 years had been ineffective, was given penicillamine 200 mg/day (188). After 10 days he became febrile and 2 days later jaundiced. A lymphocyte stimulation test against penicillamine was positive, suggesting type IV hypersensitivity. Later on he had a good response to tiopronin, without further adverse reactions. 

Mast Cell Degranulation Mast cells play a role in Type 1 hypersensitivity reactions, but they can also be stimulated by pharmaceuticals in an IgE-independent manner due to direct interactions with mast cell membranes or surface receptors (de Week, 1984). The reaction in vivo typically occurs at maximum drug concentration, or very soon after an IV infusion, and tends to diminish with subsequent exposures to the drug. Pseudoallergy is a rare event, and routine screening... 

Contact urticaria usually clears spontaneously repeated exposure may produce dermatitis (eczema). In addition, it may be associated with allergic contact dermatitis (type-IV hypersensitivity), von Krogh and Maibach [4] tested 67 patients for immediate and delayed hypersensitivity, and 22 (33%) developed a positive delayed response subsequent to the initial wheal-and-flare reaction. The responsible agents were food products, rubber latex, cinnamic aldehyde, para-aminodiphenylamine, ethylaminobenzoate, ammonium persulfate, teak, epoxy resin and lemon perfume. They suggested that the term contact dermatitis of immediate and delayed type be used for patients exhibiting both types of reactions in the test situation, whether the initial reaction is uncharacteristic, urticarial or vesicular [4]. 

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