Immunologic Disorders

Pasteur is widely quoted as saying, "Chance favors the prepared mind." This was certainly the case with Charles Richet in his discovery of hypersensitivities, commonly called allergies, near the end of the nineteenth century. Richet was a well-known physiologist who had discovered, among other things, that the acid in the stomach is hydrochloric acid. Richet also performed early experiments with antisera. He and his colleague, Paul Portier, while cruising in the South Seas on Prince Albert of Monaco's yacht, decided that the Portuguese man-of-war jellyfish must have a toxin responsible for its ugly stings. They made an extract of the tentacles of one such jellyfish and showed that it was very toxic to rabbits and ducks.

Upon returning to France, they were no longer able to study the toxins from the Portuguese man-of-war jellyfish, so they began studying the effects of toxins from the tentacles of sea anemones. Richet and Portier noted that some dogs in their experiments survived the potent toxin, but when these animals were tested with the toxin again, they died a few minutes after receiving a small dose. One very healthy dog survived the first challenge with the toxin. When given a second dose 22 days later, the dog became very ill within a few seconds. It could not breathe, lay on its side, had violent diarrhea, vomited blood, and died within 25 minutes.

Because of the insights they gained from their early work with antisera, Richet and Portier had prepared minds. They recognized that the dogs' reactions were probably immunologically mediated. The reactions, however, represented the opposite effect of prevention of disease, prophylaxis, conferred by antisera. Therefore, they named this development of hypersensitivity to relatively harmless substances anaphylaxis, the extreme opposite of prophylaxis. For this and other outstanding contributions to medicine, Richet received the Nobel Prize in 1913.

—A Glimpse of History

FOR THE MOST PART, THE IMMUNE SYSTEM DOES A superb job protecting the body from invasion by various microorganisms and viruses; however, as Richet showed, the same mechanisms that are so effective in protecting us can, under some circumstances, be detrimental. The protective responses are called immunity; immune responses that cause tissue damage are referred to as hypersensitivities. In addition to hypersensitivities, a second type of immunologic disorder, autoimmune disease, results from responses against self-antigens. A third type of immunologic disorder occurs when the immune system responds too little, resulting in immunodeficiency.

Exactly the same mechanisms occur in immunological responses, whether the reactions are protective or damaging. The immune response can be likened to fire. Fire is essential for warmth and cooking and in many ways it is beneficial, but exactly the same fire is destructive if it starts in the wrong place or becomes uncontrolled. Similarly, the immune response is essential for protection, but it can be destructive if it is out of control.

Hypersensitivity reactions to usually harmless substances are often called allergies or allergic reactions. Antigens that cause allergic reactions are allergens. Hypersensitivities are categorized according to which parts of the immune response are involved and how quickly the response occurs. Most allergic or hypersensitivity reactions fall into one of four major types:

■ Type I: Immediate IgE-mediated

■ Type III: Immune complex-mediated

■ Type IV: Delayed cell-mediated

442 Chapter 18 Immunologic Disorders

Table 18.1 Some Characteristics of the Major Types of Hypersensitivities

Characteristic

Type I hypersensitivity

Immediate;

IgE-mediated

Type II hypersensitivity Cytotoxic

Type III hypersensitivity Immune complex-mediated

Type IV hypersensitivity Delayed cell-mediated

Cell type responsible

B cells

B cells

B cells

T cells

Type of antigen

Soluble

Cell-bound

Soluble

Soluble or cell-bound

Type of antibody

IgE

IgG, IgM

IgG

None

Other cells involved

Basophils, mast cells

Red blood cells, white blood cells, platelets

Various host cells

Various host cells

Mediators

Histamine, serotonin, leukotrienes

Complement, ADCC

Complement, neutrophil proteases

Cytokines

Transfer of hypersensitivity

By serum

By serum

By serum

By T cells

Time of reaction after challenge with antigen

Immediate, up to 30 minutes

Hours to days

Hours to days

Peaks at 48 to 72 hours

Skin reaction

Wheal and flare

None

Arthus

Induration, necrosis

Examples

Anaphylactic shock, hay fever, hives

Transfusion reaction, hemolytic disease of newborns

Serum sickness, farmer's lung, malarial kidney damage

Tuberculin reaction, contact dermatitis, tissue transplant rejection

The main characteristics of the four types of hypersensitivities are shown in table 18.1. Allergic reactions occur only in sensitized individuals—that is, those who have been immunized or sensitized by prior exposure to that specific antigen.

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