Characteristics of Infectious Diseases

The acquisition of an infectious disease (e.g., viral, bacterial, parasitic, fungal) is influenced by factors related to the microorganism and host. The following factors can influence exposure to and development of an infectious disease:

In many cases, the successful dissemination of a microorganism results from spread of the microorganism over long distances by insect vectors or rapidly from country to country by global travelers. Also, some microorganisms are able to multiply in an intracellular habitat, such as in macrophages, and others can display antigen variation, which makes normal immune mechanism control difficult.

Host factors, such as the general health and age of an individual, influence the likelihood of developing an infectious disease and are important determinants of its severity. The very young and older populations develop infectious diseases more frequently than individuals in other age groups. In addition, a history of previous exposure to a disease or harboring of an organism such as a virus in a dormant condition is also a determining factor in disease development.

Development of Infectious Diseases

For an infectious disease to develop in a host, the organism must penetrate the skin or mucous membrane barrier (first line of defense) and survive other natural and adaptive body defense mechanisms (see Chapter 1). These mechanisms include phagocytosis, antibody and cell-mediated immunity or complement activation, and associated interacting effector mechanisms. Phagocytosis and complement activation may be initiated within minutes of invasion by a microorganism; however, unless primed by previous contact with the same or similar antigen, antibody and cell-mediated responses do not become activated for several days. Complement and antibodies are the most active constituents against microorganisms free in the blood or tissues, whereas cell-mediated responses are most active against microorganisms associated with cells.

The most effective mechanism of body defense in a healthy host depends on factors such as an appropriate portal of entry and the characteristics of each microorganism. The routes of infection or portals of entry can include transmission through oral routes (e.g., foodborne or water-borne contamination), maternal-fetal transmission, insect vectors, sexual transmission, parenteral routes (e.g., injection or transfusion of infected blood), and respiratory transmission. Development of an infectious disease occurs only if a microorganism can evade, overcome, or inhibit normal body defense mechanisms.

Bacterial Diseases

The presence of key substances (e.g., lysozyme) and the process of phagocytosis represent major immunologic defense mechanisms against bacteria. A microorganism, however, can survive phagocytosis if it possesses a capsule that impedes attachment or a cell wall that interferes with the digestion and release of exotoxins, which damage phagocytic and other cells. Most capsules and toxins are strongly antigenic, but antibodies can overcome many of their effects; this is the basis of most antibacterial vaccines.

Examples of representative bacterial diseases of importance in the study of immunology and serology are presented in Chapters 17 and 18.

Parasitic Diseases

Parasites are relatively large, may have resistant body walls, and may avoid being phagocytized because of their ability to migrate away from an inflamed area. These differences set parasitic infections apart from bacterial and viral infections to which some forms of natural and adaptive immunity afford protection. (Toxoplasmosis, a representative disease, is discussed in Chapter 20.)

Immune responses (effectors) to parasitic infections include immunoglobulins, complement, antibody-dependent, cell-mediated cytotoxicity, and cellular defenses such as eosinophils and T cells. Some cestodes, especially in their larval stages, may be eradicated by complement-fixing immunoglobulin G (IgG) antibodies. In addition, some antibodies may cross-react with other parasitic antigens. Increased levels of IgE may be noted in many helminth infections. Activation of the classic and alternate complement pathways may occur in some cases of schistosomiasis, and the alternate pathway of complement activation may kill larvae in the absence of antibody (see Chapter 5).

Phagocytosis may have some direct activity against parasitic organisms, but the most effective protection in some parasitic infections is provided by antibody-dependent, cell-mediated cytotoxicity. Macrophages, neutrophils, and eosinophils may demonstrate direct toxicity or phagocytosis toward parasites. The actual attachment of the cytotoxic cells is usually mediated by IgG, although IgE may be effective. The role of eosinophils is complex. They may phagocytize immune complexes and act as effector cells in mediating local (type I) reactions, primarily in tissue stage parasites. T cells are frequently involved in body defenses against parasites. Sequestration of microorganisms is a classic T-cell–dependent hypersensitivity response. In addition, helper T cells may sensitize B cells to specific parasitic antigens.

Other nonspecific factors (e.g., nonstimulated monocytes) are a major protective mechanism against parasites such as Giardia spp. Natural killer (NK) cells also have a direct activity against cancer cells and some parasites. Delayed hypersensitivity may be helpful in preventing some parasitic infections but may cause disease in other cases. Deposition of antigen-antibody complexes, demonstrated by Raji cell assays, is responsible for severe pathologic lesions in some parasitic infections. In addition, high levels of circulating IgE may cause hypersensitivity reactions in helminth and cestode infections. Anaphylaxis is a clear risk in echinococcal infections, especially with spontaneous or surgical rupture of a hydatid cyst.

Fungal Diseases

Fungal, or mycotic, infections are normally superficial, but a few fungi can cause serious systemic disease, usually entering through the respiratory tract in the form of spores. Disease manifestation depends on the degree and type of immune response elicited by the host. Fungi are common and harmless inhabitants of skin and mucous membranes under normal conditions (e.g., Candida albicans). In immunocompromised hosts, Candida spp. and other fungi become opportunistic agents that take advantage of the host’s weakened resistance. Manifestations of fungal disease may range from unnoticed respiratory episodes to rapid, fatal dissemination of a violent hypersensitivity reaction.

Survival mechanisms of fungi that successfully invade the body are similar to bacterial characteristics and include the following: (1) presence of an antiphagocytic capsule; (2) resistance to digestion within macrophages; and (3) destruction of phagocytes (e.g., neutrophils). Some types of yeast activate complement through the alternative pathway, but it is unknown whether this activation has any effect on the microorganism’s survival.

Fungal infections are increasing worldwide for a variety of reasons, including the use of immunosuppressive drugs and the development of diseases that result in an immunocompromised host (e.g., acquired immune deficiency syndrome [AIDS]). Serologic tests often play an important role in the diagnosis of these fungal infections (Table 15-1).

Several species of fungi are associated with respiratory disease in human beings. These diseases are acquired by inhaling spores from exogenous reservoirs, including dust, bird droppings, and soil.