DE LOS CLUBES

The patch test is considered the gold standard in testing for contact dermatitis.42,44_{This must be done when the patient}

is free of symptoms or when he or she at least has a clear test site. A nonabsorbent adhesive patch containing the sus- pected allergen is applied on the patient’s back, and the skin is checked for a reaction over the next 48 hours. Redness with papules or tiny blisters is considered a positive test. Final evaluation is conducted at 96 to 120 hours. All read- ings should be done by a skilled evaluator. False negatives can result from inadequate contact with the skin.

Another type of skin test for delayed hypersensitivity, the Mantoux method, is performed in much the same manner as

testing for the presence of IgE. Typically, 0.1 mL of the anti- gen is injected intradermally, using a syringe and a fine needle.7,46_{The test site is read at 48 and 72 hours for the}

presence of induration. An induration of 5 mm or more is considered a positive test.46_{Antigens typically used for test-}

ing are Candida albicans, tetanus toxoid, tuberculin, and fungal antigens such as trichophyton and histoplasmin.46

SUMMARY

Hypersensitivity reactions are exaggerated reactions to anti- gens that are typically not harmful. Usually there is destruction of host tissue in the process of attempting to destroy the antigen. Gell and Coombs devised a system of classification for such reactions based on immune media- tors and the nature of the triggering antigen. Type I hypersensitivity, or immediate hypersensitivity, is manifested within minutes of exposure to antigen. The principle medi- ator is IgE, which does not remain free in the serum but binds to mast cells and basophils. When cell-bound anti- body binds antigen, the resulting degranulation of the effector cells releases mediators that enhance the inflamma- tory response. Preformed mediators that are released include histamine, eosinophil chemotactic factor of anaphylaxis, neutrophil chemotactic factor, and proteolytic enzymes such as tryptase. Together, these factors are responsible for con- traction of smooth muscle in the bronchioles, blood vessels, and intestines; increased capillary permeability; increased concentration of eosinophils and neutrophils in the area; and decreased coagulability of blood. Newly synthesized mediators, such as prostaglandins, leukotrienes, and PAF, potentiate the effects of histamine and other preformed mediators.

Clinical manifestations of immediate hypersensitivity include localized wheal and flare skin reactions; rhinitis; and systemic anaphylactic responses, which can be life- threatening. Tests to determine the potential for incurring such reactions include both in vitro and in vivo methods. The noncompetitive RIST measures total IgE by using radi- olabeled anti-IgE that binds to patient’s IgE on solid phase. RAST is a noncompetitive or capture method to determine antibody to specific allergens. In vivo skin tests such as the prick or intradermal tests are done by exposing the patient directly to a very small amount of allergen injected under the skin. A positive test produces a wheal and flare reaction. The reactants responsible for type II hypersensitivity are IgG and IgM. They react with antigens located on cellular surfaces and trigger activation of the complement cascade. Target cells are damaged or destroyed by the opsonizing effect of antibody or complement components or by complement-generated lysis if the cascade goes to comple- tion. Examples of type II reactions due to exogenous antigens include autoimmune hemolytic anemia, transfu- sion reactions, and HDN.

The DAT is used to screen for transfusion reactions, autoimmune hemolytic anemia, and hemolytic disease of

CHAPTER 13 Hypersensitivity 217

the newborn. Washed patient red blood cells are combined with antihuman globulin and observed for agglutination, indicating the presence of IgG or complement components on the cells.

Goodpasture’s syndrome is an example of a type II reac- tion directed against a self-antigen in tissue. This syndrome is the result of antibody that reacts with the basement mem- brane of the glomerulus. Complement is activated, causing tissue damage and eventual loss of renal function.

In type III hypersensitivity reactions, IgG, IgM, and com- plement are also involved, but the reaction is directed against soluble rather than cellular antigens. If mild antigen excess occurs, the antigen–antibody complexes precipitate out and deposit in the tissues. The sites most affected are the base- ment membrane in the kidneys, the linings of blood vessels, and the joint linings. When complement binds to these complexes, phagocytic cells are attracted to the area. If the target cells cannot be engulfed, a reverse-phagocytic process called exocytosis takes place. The Arthus reaction, charac- terized by deposition of antigen–antibody complexes in the

blood vessels, is a classic example of a type III reaction. Other examples include serum sickness and autoimmune diseases such as SLE and rheumatoid arthritis. Specific tests can be performed to determine the nature of the antibody involved.

Type IV, or delayed, hypersensitivity differs from the other three categories in that antibody and complement do not play a major role. Activation of T cells with the subse- quent release of cytokines is responsible for the tissue damage seen in this type of reaction. Contact dermatitis resulting from exposure to poison ivy, poison oak, or a metal such as nickel is an example of haptens triggering a reaction to self-antigens. Skin testing and lymphocyte activation are used to determine sensitivity to particular antigens.

All four types of hypersensitivity represent defense mech- anisms that stimulate an inflammatory response to cope with and react to antigen that is seen as foreign. In many cases, the antigen is not harmful, but the response to it results in tissue damage. This necessitates treatment to limit the damage.

218 SECTION 3 Immune Disorders

1. A 13-year-old male had numerous absences from school in the spring due to cold symptoms that included head congestion and cough. He had been on antibiotics twice, but he seemed to go from one cold to the next. A complete blood cell (CBC) count showed no overall increase in white blood cells, but a mild eosinophilia was present. Because he had no fever or other signs of infection, his physician suggested that a total IgE screen- ing test be run. The total IgE value was 250 IU/mL, which was within high-normal limits.

Questions

a. What would account for the eosinophilia noted? b. What conclusions can be drawn from the total IgE

value?

c. What other tests might be indicated?

2. A 55-year-old male went to his physician complaining of feeling tired and run down. Two months previously,

he had pneumonia and was concerned that he might not have completely recovered. He indicated that his symptoms only become noticeable if he goes out in the cold. A CBC count was performed, showing that his white cell count was within normal limits, but his red cell count was just below normal. A DAT performed on red blood cells was weakly positive after incubating at room temperature for 5 minutes. When the DAT was repeated with monospecific reagents, the tube with anti- C3d was the only one positive.

Questions

a. What does a positive DAT indicate?

b. What is the most likely class of the antibody caus- ing the reaction?

c. Why was the DAT positive only with anti-C3d when monospecific reagents were used?