An antigen, or immunogen, is defined as any substance that is capable of stimulating immune cells (T and B cells) to induce an immune response. Antigens can be broadly divided into two large categories: (1) infectious (microbial) and (2) noninfectious (Figure 54-1). Infectious antigens include components that are derived from bacteria, viruses, protozoa, and helminths. Noninfectious antigens include those derived from “self” (autoantigens), food, plants, dust, or insect and animal venoms, as well as synthetic and cell surface proteins.

An antigen is composed of many molecular units to which an antibody binds. These small units on an antigen are called antigenic epitopes, or antigenic determinants. Thus a single antigen may be composed of many antigenic epitopes. In the strictest sense, antibodies bind to an antigenic epitope of an antigen. Some of these antigenic epitopes are shared among different bacteria (e.g., epitopes on Brucella and Yersinia) or between a bacteria and host cells (e.g., Mycobacterium heat shock proteins and synovial tissue; Mycoplasma and lung tissue). These types of antigenic epitopes are called cross-reactive epitopes.

Figure 54-2 shows the following antigenic structures of bacteria:

Viruses have nucleic acids (ribonucleic acid [RNA] or DNA), surrounded by a protein coat called a capsid. Some viruses have an envelope, a lipid membrane–like structure covering the capsid. On the envelope are glycoprotein projections that the viruses use to attach to the host target cells. All these components may be antigenic.

External structures of protozoa and helminths tend to be antigenic. Similarly, fungal spores are antigenic. Pollens, glycoproteins of certain foods, the unique biochemical structure of synthetic chemicals, insect saliva, and venoms are all good antigens. It is beyond the scope of this chapter to discuss each of these antigens in detail.

The immune system is exposed to and tolerates “self” antigens found on all of its own tissues. These antigens can be cell surface antigens (e.g., thyroglobulin, myelin peptides) or internal antigens (e.g., cardiolipin, nucleic acids, histones). In certain individuals who are allergic, antigens derived from food (e.g., peanuts, strawberries, fish) or plants (e.g., pollen, spores) induce an immediate and potent immune reaction. Many synthetic chemicals and drugs are minute in size and tend to be adsorbed onto cell surface antigens to create a new antigenic epitope. With ever-increasing synthesis of chemicals (pesticides, agricultural chemicals, drugs, and consumer products, to name a few), it is likely that synthetic chemicals may become an important class of antigens in the future.

The body is confronted with literally billions of antigens. Consequently, a unique challenge presented to the immune system is to respond effectively only to foreign antigens while refraining from response to “self” antigens. The induction of immune responses requires energy and protein, and antigens require extensive cellular division (and hence utilization of protein reserves); the body cannot mount immune responses to each of the innumerable antigens it encounters constantly. Instead, the body is well equipped to handle antigens effectively before resorting to a specific immune response.

Initially, most antigens are effectively handled by nonspecific defense mechanisms, such as impervious and formidable physical barriers (e.g., skin and other body surfaces) and antimicrobial body fluids (e.g., lysozymes in tears, saliva, gastric juices). These are considered the first line of defense and are discussed next. Should the antigen survive this “body armor,” phagocytic cells (e.g., neutrophils, macrophages-monocytes) and natural killer (NK, NK-T) cells can effectively eliminate the invading antigens. These cells ingest and destroy a wide range of antigens and thus are non–antigen-specific. These cellular defenses constitute a second line of the body’s defense. The body’s initial defense (physical, chemical, and phagocytic antigen-presenting cells; natural killer cells) constitute the innate immune system. The antigen-presenting cells closely interact with specific T and B cells to induce a specific immune response. Thus, specific immune responses by the “adaptive” immune system tend to be the last line of the body’s defense (see Chapter 55). Collectively, both nonimmune and immune mechanisms effectively counter invading microbes.