Allergic Reactions

Both allergic reactions and immune responses entail sensitizing of lymphocytes or combining of antigens with antibodies. An allergic reaction, however, is an immune attack against a nonharmful substance, and can damage tissues. An allergy is also called a hypersensitivity reaction. One form of allergic reaction can occur in almost anyone, but another form affects only people who have inherited an ability to produce exaggerated immune responses. The antigens that trigger allergic responses are called allergens (al'er-jenz).

An immediate-reaction (type I or anaphylactic) allergy occurs within minutes after contact with an allergen. Persons with this type of allergy have an inherited tendency to overproduce IgE antibodies in response to certain antigens. IgE normally comprises a tiny fraction of plasma proteins.

An immediate-reaction allergy activates B cells, which become sensitized when the allergen is first encountered. Subsequent exposures to the allergen trigger allergic reactions. In the initial exposure, IgE attaches to the membranes of widely distributed mast cells and basophils. When a subsequent allergen-antibody reaction occurs, these cells release allergy mediators such as histamine, prostaglandin D2, and leukotrienes (fig. 16.24). These substances cause a variety of physiological effects, including dilation of blood vessels, increased vascular permeability that swells tissues, contraction of bronchial and intestinal smooth muscles, and increased mucus production. The result is a severe inflammation reaction that is responsible for the symptoms of the allergy, such as hives, hay fever, asthma, eczema, or gastric disturbances.

Anaphylactic shock is a severe form of immediate-reaction allergy, in which mast cells release allergy mediators throughout the body. The person may at first feel an inexplicable apprehension, and then suddenly the entire body itches and breaks out in red hives. Vomiting and diarrhea may follow. The face, tongue, and larynx begin to swell, and breathing becomes difficult. Unless the person receives an injection of epinephrine (adrenaline) and sometimes a tracheotomy (an incision into the windpipe so that breathing is restored), he or she will lose consciousness and may die within five minutes. Anaphylac-tic shock most often results from an allergy to penicillin or insect stings. Fortunately, thanks to prompt medical attention and people who know they have allergies avoiding the allergens, fewer than 100 people a year actually die of anaphylactic shock.

One theory of the origin of allergies, particularly anaphylactic shock, is that they evolved at a time when insect bites and the natural substances from which antibiotics such as penicillin are made threatened human survival. Today, that once-protective response is an overreaction. The observation that IgE protects against roundworm and flatworm infections, in addition to taking part in allergic reactions, supports the idea that this antibody class is a holdover from times past, when challenges to the immune system differed from what they are today.

Hypersensitivities that take one to three hours to develop include antibody-dependent cytotoxic reactions (type II) and immune complex reactions (type III). In an antibody-dependent cytotoxic reaction, an antigen binds to a specific cell, stimulating phagocytosis and complement-mediated lysis of the antigen. A transfusion reaction to mismatched blood is a type II hypersensitivity reaction. In an immune complex reaction, widespread antigen-antibody complexes cannot be cleared from the circulation by phagocytosis and lysis. As a result, the complexes may block small vessels, which damages the tissues that they reach. Autoimmunity, the loss of the ability to tolerate self antigens, illustrates this type of hypersensitivity reaction. It is discussed later in the chapter in the section titled "Autoimmunity."

tion. The transplanted tissue may also produce substances that harm the recipient's tissue, a response called graft-versus-host disease (GVHD).

Tissue rejection resembles the cellular immune response against a foreign antigen. The greater the anti-genic difference between the cell surface molecules of the recipient tissues and the donor tissues, the more rapid and severe the rejection reaction. Matching the cell surface molecules of donor and recipient tissues can minimize the rejection reaction. This means locating a donor whose tissues are antigenically similar to those of the person needing a transplant—a procedure much like matching the blood of a donor with that of a recipient before giving a blood transfusion.

The four major varieties of grafts (transplant tissue) include

• Isograft. Tissue is taken from a genetically identical twin.

The tuberculin skin test is used to detect individuals who have tuberculosis (TB) or who have had it (or a closely related infection) or been exposed to it. The test uses a tuberculin preparation called purified protein derivative (PPD), which is introduced into the superficial layers of the skin (Mantoux test). If the person's T cells have been sensitized to the antigens of the mycobacteria that cause tuberculosis, an allergic reaction (positive test result) occurs within forty-eight to seventy-two hours. In a positive reaction, a localized region of the skin and subcutaneous tissue hardens (indurates). The absence of this reaction (negative result) signifies that the person's T cells have not previously encountered the mycobacterial antigens.

• Autograft. Tissue is taken from elsewhere in a person's body, as in the case of skin grafts. (Technically, this is not a transplant because it occurs within an individual.)

• Allograft. Tissue comes from an individual who is not genetically identical to the recipient, but of the same species.

• Xenograft. Tissue comes from a different species, such as pigs and baboons.

Table 16.9 presents examples of transplants.

A delayed-reaction allergy (type IV) may affect anyone. It results from repeated exposure of the skin to certain chemicals—commonly, household or industrial chemicals or some cosmetics. After repeated contacts, the presence of the foreign substance activates T cells, many of which collect in the skin. The T cells and the macrophages they attract release chemical factors, which, in turn, cause eruptions and inflammation of the skin (dermatitis). This reaction is called delayed because it usually takes about forty-eight hours to occur.

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