Porth's Essentials of Pathophysiology, 4e

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Infection and Immunity

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complexes in blood vessels, joints, and heart and kidney tissue. 2,3 The deposited complexes activate complement, increase vascular permeability, and recruit phagocytic cells, all of which can promote local tissue damage and edema. The term serum sickness was originally coined to describe a syndrome consisting of rash, lymphade- nopathy, arthralgias, and occasionally neurologic disor- ders that appeared 7 or more days after injections of horse antiserum (used in protecting against tetanus). Although this therapy is not used today, the name remains. Currently, the most common causes of this allergic disorder include antibiotics (especially penicil- lin) and other drugs, various foods, and insect venoms. The signs and symptoms of systemic immune com- plex disorders include urticaria, patchy or generalized rash, extensive edema (usually of the face, neck, and joints), and fever. In most cases, the damage is tempo- rary, and symptoms resolve within a few days. However, a prolonged and continuous exposure to the sensitizing antigen can lead to irreversible damage. In previously sensitized persons, severe and even fatal forms of serum sickness may occur immediately or within several days after the sensitizing drug or serum is administered. Treatment usually is directed toward removal of the sen- sitizing antigen and providing symptomatic relief. This may include aspirin for joint pain and antihistamines for pruritus (itching). Epinephrine or systemic cortico- Arthus reaction is a term used by pathologists and immu- nologists to describe localized tissue necrosis (usually in the skin) caused by type III immune complexes. In the laboratory, an Arthus reaction can be produced by inject- ing an antigen preparation into the skin of an immune animal with high levels of circulating antibody. Within 4 to 10 hours, a red, raised lesion appears on the skin at the site of the injection. 2 An ulcer often forms in the center of the lesion. It is thought that the injected anti- gen diffuses into local blood vessels, where it comes in contact with specific antibody (IgG) to incite a local- ized vasculitis (i.e., inflammation of a blood vessel). This experimental model of localized vasculitis is the proto- type of many forms of vasculitis seen in humans, such as the cutaneous vasculitides that characterize certain drug reactions. Type IV hypersensitivity reactions involve cell-mediated rather than antibody-mediated immune responses. 2,3 Cell-mediated immunity is the principal mechanism of response to a variety of microorganisms, includ- ing intracellular pathogens such as Mycobacterium tuberculosis and viruses, as well as extracellular agents such as fungi, protozoa, and parasites. It can also lead to cell death and tissue injury in response to chemical antigens (contact dermatitis) or self-antigens (autoimmunity). steroids may be used for severe reactions. Local Immune Complex Reactions Type IV, Cell-Mediated Hypersensitivity Disorders

Antigen

Antigen- presenting cell

CD8 + T cell

Primed CD4 + T cell

Direct cell toxicity

Target cell

Activated CD4 + T cell

A

Cytokines

Delayed hypersensitivity response

B FIGURE 16-4. Type IV, cell-mediated hypersensitivity reactions, which include (A) direct cell-mediated cytotoxicity in which CD8 + T cells kill the antigen-bearing target cells, and (B) delayed-type hypersensitivity reactions in which presensitized CD4 + cells release cell-damaging cytokines.

Type IV hypersensitivity reactions, which are medi- ated by specifically sensitized T lymphocytes, can be divided into two basic types: direct cell-mediated cyto- toxicity and delayed-type hypersensitivity (Fig. 16-4). Direct Cell-Mediated Cytotoxicity In direct cell-mediated cytotoxicity (see Fig. 16-4A), CD8 + cytotoxic T lymphocytes (CTLs) directly kill tar- get cells that express peptides derived from cytosolic antigens that are presented in association with class I major histocompatibility complex (MHC) molecules (see Chapter 15). In viral infections, CTL responses can lead to tissue injury by killing infected target cells even if the virus itself has no cytotoxic effects. 2 Because CTLs cannot distinguish between cytopathic and non- cytopathic viruses, they kill virtually all infected cells regardless of whether the infection is harmful. In certain forms of hepatitis, for example, the destruction of liver cells is due to the host CTL response and not the virus.