Porth's Essentials of Pathophysiology, 4e

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Infection and Immunity

U N I T 4

host that can stimulate an immune response. These for- eign molecules are recognized by receptors on immune cells and by secreted proteins, called antibodies or immu- noglobulins, made in response to the antigen. Antigens include bacteria, fungi, viruses, protozoa, and parasites. Nonmicrobial agents such as plant pollens, poison ivy resin, insect venom, and transplanted organs can also act as antigens. Although most antigens are macromol- ecules, such as proteins and polysaccharides, lipids and nucleic acids occasionally serve as antigens. Antigens, which in general are large and chemically complex, are biologically degraded into smaller chemical units or peptides. These discrete, immunologically active sites on antigens are called antigenic determinants, or epitopes . It is the unique molecular shape of the epitope that is recognized by a specific immunoglobulin receptor found on the surface of a lymphocyte or by an antigen- binding site of a secreted antibody (Fig. 15-5). A single antigen may contain multiple antigenic determinants, each stimulating a distinct clone of T and B lympho- cytes. For example, different proteins that comprise the influenza virus may function as unique antigens (A, B, C, H, and N antigens), each of which contains several anti- genic determinants. Hundreds of antigenic determinants are found on structures such as the bacterial cell wall. Smaller substances (molecular masses <10,000 dal- tons) usually are unable to stimulate an adequate immune response by themselves. When these low–molecular- weight compounds, known as haptens, combine with larger carrier molecules, they function as antigens. The hapten–carrier complex can stimulate the production of antibodies, some of which combine with the hapten portion of the complex. An allergic response to the anti- biotic penicillin is an example of a medically important reaction due to hapten–carrier complexes. Penicillin (molecular mass of approximately 350 daltons) is

normally a nonantigenic molecule. However, in some individuals, it can chemically combine with body pro- teins to form larger complexes that can then generate a potentially harmful immune allergic response. Cells and Molecules of Adaptive Immunity B and T lymphocytes are the effector cells of the adap- tive immune system that specifically recognize and respond to foreign antigens. Accessory cells, such as macrophages and dendritic cells, function as antigen- presenting cells by first processing a complex antigen into epitopes and then displaying the foreign and self- peptides on their membranes so that appropriate acti- vation of lymphocytes occurs. We will begin with a discussion of the antigen-presenting cells, move to the lymphocytes, and end with the MHC molecules that dis- play antigens for recognition by T lymphocytes. Antigen-Presenting Cells Macrophages are key members of the mononuclear phagocytic system that engulf and digest microbes and other foreign substances. The monocytes migrate from the blood to various tissues, where they mature into the major tissue phagocytes, the macrophages. As the gen- eral scavenger cells of the body, the macrophages can be fixed in a tissue or free to migrate from an organ to lymphoid tissues. The tissue macrophages are scat- tered in connective tissue or may be clustered in the lung (alveolar macrophages), liver (Kupffer cells), spleen, lymph nodes, peritoneum, or central nervous system (microglial cells). Dendritic cells are found in most tissues where anti- gen enters the body and in the peripheral lymphoid tis- sues, where they function as potent antigen-presenting cells. In these environments, dendritic cells can acquire specialized functions and appearances, as do macro- phages. Langerhans cells are specialized dendritic cells in the skin, whereas follicular dendritic cells are found in the lymph nodes. Langerhans cells are constantly sur- veying the skin for antigen and can transport foreign material to a nearby lymph node. Skin dendritic cells and macrophages also are involved in cell-mediated immune reactions of the skin such as allergic contact dermatitis. Lymphocytes Like other blood cells, B and T lymphocytes are generated from stem cells in the bone marrow. Undifferentiated, immature lymphocytes move to the central lymphoid tissues, where they develop into distinct types of mature lymphocytes (Fig. 15-6). B lymphocytes mature in the bone marrow and then move to the peripheral lymphoid tissues where they are exposed to antigen and stimulated to differentiate into antibody-producing plasma cells. T lymphocytes complete their maturation in the thy- mus and then move to the peripheral lymphoid tissues, where they function to produce cell-mediated immunity,

Epitopes (antigenic determinants)

Antibody A

Antigen- binding sites

Antigen

Antibody B

Antibody C

FIGURE 15-5. Multiple epitopes on a complex antigen being recognized by their respective (A, B, C) antibodies.