Host-Microorganism Interactions
1. List the various reservoirs (environments) that facilitate host-microorganism interactions.
2. Define direct versus indirect transmission and provide examples of each.
3. Define and differentiate the interactions between the host and microorganism, including colonization, infection, normal (resident) flora, pathogens, opportunistic pathogens, and nosocomial infection.
4. List and describe the components involved in specific versus nonspecific immune defenses, including inflammation, phagocytosis, antibody production, and cellular responses.
5. Identify elements involved in the two arms of the immune system: humoral and cell-mediated immunity.
6. Provide specific examples of disease prevention strategies, including preventing transmission, controlling reservoirs and minimizing risk of exposure.
7. Differentiate between bacterial endotoxins and exotoxins and provide examples of each.
8. Given a patient history of an infectious process, identify and differentiate a sign versus a symptom.
9. Define and differentiate between an acute infectious process and one that is chronic and/or latent.
Interactions between humans and microorganisms are exceedingly complex and far from being completely understood. What is known about the interactions between these two living entities plays an important role in the practice of diagnostic microbiology and in the management of infectious disease. Understanding these interactions is necessary for establishing methods to reliably isolate specific microorganisms from patient specimens and for developing effective treatment strategies. This chapter provides the framework for understanding the various aspects of host-microorganism interactions. Box 3-1 lists a variety of terms and definitions associated with host-microorganism interactions.
Host-microorganism interactions should be viewed as bidirectional in nature. Humans use the abilities and natural products of microorganisms in various settings, including the food and fermentation industry, as biologic insecticides for agriculture; to genetically engineer a multitude of products; and even for biodegrading industrial waste. However, microbial populations share the common goal of survival with humans, using their relationship with humans for food, shelter, and dissemination, and they have been successful at achieving those goals. Which participant in the relationship is the user and which is the used becomes a fine and intricate balance of nature. This is especially true when considering the microorganisms most closely associated with humans and human disease.
The complex relationships between human hosts and medically relevant microorganisms are best understood by considering the sequential steps in the development of microbial-host associations and the subsequent development of infection and disease. The stages of interaction (Figure 3-1) include (1) the physical encounter between host and microorganism; (2) colonization or survival of the microorganism on an internal (gastrointestinal, respiratory, or genitourinary tract) or external (skin) surface of the host; (3) microbial entry, invasion, and dissemination to deeper tissues and organs of the human body; and (4) resolution or outcome.
The Encounter Between Host and Microorganism
The Human Host’s Perspective
Because microorganisms are found everywhere, human encounters are inevitable, but the means of encounter vary widely. Which microbial population a human is exposed to and the mechanism of exposure are often direct consequences of a person’s activity or behaviors. Certain activities carry different risks for an encounter, and there is a wide spectrum of activities or situations over which a person may or may not have absolute control. For example, acquiring salmonellosis because one fails to cook the holiday turkey thoroughly is avoidable, whereas contracting tuberculosis as a consequence of living in conditions of extreme poverty and overcrowding may be unavoidable. The role that human activities play in the encounter between humans and microorganisms cannot be overstated, because most of the crises associated with infectious disease could be avoided or greatly reduced if human behavior and living conditions could be altered.
Microbial Reservoirs and Transmission
Humans encounter microorganisms when they enter or are exposed to the same environment in which the microbial agents live or when the infectious agents are brought to the human host by indirect means. The environment, or place of origin, of the infecting agent is referred to as the reservoir. As shown in Figure 3-2, microbial reservoirs include humans, animals, water, food, air, and soil. The human host may acquire microbial agents by various means referred to as the modes of transmission. The mode of transmission is direct when the host directly contacts the microbial reservoir and is indirect when the host encounters the microorganism by an intervening agent of transmission.
The agents of transmission that bring the microorganism from the reservoir to the host may be a living entity, such as an insect, in which case they are called vectors, or they may be a nonliving entity, referred to as a vehicle or fomite. Additionally, some microorganisms may have a single mode of transmission, whereas others may spread by various methods. From a diagnostic microbiology perspective, knowledge about an infectious agent’s mode of transmission is often important for determining optimum specimens for isolation of the organism and for implementing precautions that minimize the risk of laboratory-acquired infections (see Chapters 4 and 80 for more information regarding laboratory safety).
Human and Microbe Interactions
Humans play a substantial role as microbial reservoirs. Indeed, the passage of a neonate from the sterile environment of the mother’s womb through the birth canal, which is heavily colonized with various microbial agents, is a primary example of one human directly acquiring a microorganism from another human serving as the reservoir. This is the mechanism by which newborns first encounter microbial agents. Other examples in which humans serve as the microbial reservoir include acquisition of “strep” throat through touching; hepatitis through blood transfusions; gonorrhea, syphilis, and acquired immunodeficiency syndrome through sexual contact; tuberculosis through coughing; and the common cold through sneezing. Indirect transfer can occur when microorganisms from one individual contaminate a vehicle of transmission, such as water (e.g., cholera), that is then ingested by another person. In the medical setting, indirect transmission of microorganisms from one human host to another by means of contaminated medical devices helps disseminate infections in hospitals. Hospital-acquired, health care−, or long-term care−associated infections are referred to as nosocomial infections.
Animals as Microbial Reservoirs
Infectious agents from animal reservoirs can be transmitted directly to humans through an animal bite (e.g., rabies) or indirectly through the bite of insect vectors that feed on both animals and humans (e.g., Lyme disease and Rocky Mountain spotted fever). Animals may also transmit infectious agents by acquiring or depositing them in water and food supplies. For example, beavers are often heavily colonized with parasites that cause infection of the human gastrointestinal tract. These parasites may be encountered and subsequently acquired when stream water becomes contaminated by the beaver and is used by the vacationing camper. Alternatively, animals used for human food carry numerous bacteria (e.g., Salmonella and Campylobacter) that, if not destroyed through appropriate cooking during preparation, can cause severe gastrointestinal illness.
Many other infectious diseases are encountered through direct or indirect animal contact, and information regarding a patient’s exposure to animals is often a key component in the diagnosis of these infections. Some microorganisms primarily infect animal populations and on occasion accidentally encounter and infect humans. When a human infection results from such an encounter, it is referred to as a zoonotic infection.
Insects as Vectors
The most common role of insects (arthropods) in the transmission of infectious disease is as vectors rather than as reservoirs. A wide variety of arthropods transmit viral, parasitic, and bacterial disease from animals to humans, whereas others transmit microorganisms between human hosts without an intermediate animal reservoir. Malaria, a deadly disease, is a prime example of an infectious disease maintained in the human population by the feeding and survival of an insect vector, the mosquito. Still other arthropods may themselves be agents of disease. These include organisms such as lice and scabies, which are spread directly between humans and cause skin irritations but do not penetrate the body. Because they are able to survive on the skin of the host without gaining access to internal tissues, they are referred to as ectoparasites. In addition, nonfungal infections (e.g., tetanus) may result when microbial agents in the environment, such as endospores, are mechanically introduced by the vector as a result of a bite, scratch, or other penetrating wound.
The Environment as a Microbial Reservoir
The soil and natural environmental debris are reservoirs for countless types of microorganisms. Therefore, it is not surprising that these also serve as reservoirs for microorganisms that can cause infection in humans. Many of the fungal agents (see Part V: Mycology) are acquired by inhalation of soil and dust particles containing microorganisms (e.g., San Joaquin Valley fever). Other, nonfungal infections (e.g., tetanus endospores) may result when microbial agents in the environment are introduced into the human body as a result of a penetrating wound.
The Microorganism’s Perspective
Clearly, numerous activities can result in human encounters with many microorganisms. Because humans are engaged in all of life’s complex activities, the tendency is to perceive the microorganism as having a passive role in the encounter process. However, this assumption is a gross oversimplification.
Microorganisms are also driven by survival, and the environment of the reservoirs they occupy must allow their metabolic and genetic needs to be fulfilled. Reservoirs maybe inhabited by hundreds or thousands of different species of microorganisms. Yet human encounters with the reservoirs, either directly or indirectly do not result in all species establishing an association with the human host. Although some species have evolved strategies that do not involve the human host to ensure survival, others have included humans to a lesser or greater extent as part of their survival tactics. Therefore, the latter type of organism often has mechanisms that enhance its chances for human encounter.
Depending on factors associated with both the human host and the microorganism involved, the encounter may have a beneficial, disastrous, or inconsequential impact on each of the participants.
Microorganism Colonization of Host Surfaces
The Host’s Perspective
Once a microbe and the human host are brought into contact, the outcome of the encounter depends on what happens during each step of interaction (see Figure 3-1), beginning with colonization. The human host’s role in microbial colonization, defined as the persistent survival of microorganisms on a surface of the human body, is dictated by the defenses that protect vital internal tissues and organs against microbial invasion. The first defenses are the external and internal body surfaces that are in direct contact with the external environment and are the anatomical regions where the microorganisms will initially come in contact with the human host. These surfaces include:
• Skin (including conjunctival epithelium covering the eye)
• Mucous membranes lining the mouth or oral cavity, the respiratory tract, the gastrointestinal tract, and the genitourinary tract
Because body surfaces are always present and provide protection against all microorganisms, skin and mucous membranes are considered constant and nonspecific protective mechanisms. As is discussed later in this text, other protective mechanisms are produced in response to the presence of microbial agents (inducible defenses), and some are directed specifically at particular microorganisms or (specific defense mechanisms).
Skin and Skin Structures
Skin serves as a physical and chemical barrier to microorganisms; its protective characteristics are summarized in Table 3-1 and Figure 3-3. The acellular, outermost layer of the skin, along with the tightly packed cellular layers underneath, provide an impenetrable physical barrier to all microorganisms, unless damaged. Additionally, these layers continuously shed, thus dislodging bacteria that have attached to the outer layers. The skin is also a dry and cool environment; this is incompatible with the growth requirements of many microorganisms, which thrive in a warm, moist environment.
TABLE 3-1
Protective Characteristics of the Skin and Skin Structures
| Skin Structure | Protective Activity |
| Outer (dermal) layers | |
| Hair follicles, sweat glands, sebaceous glands | |
| Eyes/conjunctival epithelium | |
| Skin-associated lymphoid tissue |
The follicles and glands of the skin produce various natural antibacterial substances, including sebum and sweat. However, many microorganisms can survive the conditions of the skin. These bacteria are known as skin colonizers, and they often produce substances that may be toxic and inhibit the growth of more harmful microbial agents. Beneath the outer layers of skin are various host cells that protect against organisms that breach the surface barriers. These cells, collectively known as skin-associated lymphoid tissue, mediate specific and nonspecific responses directed at controlling microbial invaders.
Mucous Membranes
Because cells that line the respiratory tract, gastrointestinal tract, and genitourinary tract are involved in numerous functions besides protection, they are not covered with a hardened, acellular layer as is the skin surface. However, the cells that compose these membranes still exhibit various protective characteristics (Table 3-2 and Figure 3-4).
TABLE 3-2
Protective Characteristics of Mucous Membranes
| Mucous Membrane | Protective Activity |
| Mucosal cells | |
| Goblet cells | |
| Mucosa-associated lymphoid tissue |
General Protective Characteristics.
Mucus is a major protective component of the membranes. This substance serves to trap bacteria before they can reach the outer surface of the cells, lubricates the cells to prevent damage that promotes microbial invasion, and contains specific chemical (i.e., antibodies) and nonspecific antibacterial substances. In addition to the chemical properties and physical movement of the mucus and trapped microorganisms mediated by ciliary action, rapid cellular shedding and tight intercellular connections provide effective barriers to infection. As is the case with the skin, specific cell clusters, known as mucosa-associated lymphoid tissue, exist below the outer cell layer and mediate specific protective mechanisms against microbial invasion.
Specific Protective Characteristics.
Besides the general protective properties of mucosal cells, the mucosal linings throughout the body have characteristics specific to each anatomic site (Figure 3-5).
The mouth, or oral cavity, is protected by the flow of saliva that physically carries microorganisms away from cell surfaces and also contains antibacterial substances, such as antibodies (IgA) and lysozyme that participate in the destruction of bacterial cells. The mouth is also heavily colonized with protective microorganisms that produce substances that hinder successful invasion by harmful organisms.
In the gastrointestinal tract, the low pH and proteolytic (protein-digesting) enzymes of the stomach prevent the growth of many microorganisms. In the small intestine, protection is provided through the presence of bile salts, which disrupt bacterial membranes, and by peristaltic movement and the fast flow of intestinal contents, which hinder microbial attachment to mucosal cells. Although the large intestine also contains bile salts, the movement of bowel contents is slower, permitting a higher concentration of microbial agents the opportunity to attach to the mucosal cells and inhabit the gastrointestinal tract. As in the oral cavity, the high concentration of normal microbial inhabitants in the large bowel also contributes significantly to protection.
In the upper respiratory tract, nasal hairs keep out large airborne particles that may contain microorganisms. The cough-sneeze reflex significantly contributes to the removal of potentially infective agents. The cells lining the trachea contain cilia (hairlike cellular projections) that move microorganisms trapped in mucus upward and away from the delicate cells of the lungs (see Figure 3-4); this is referred to as the mucociliary escalator. These barriers are so effective that only inhalation of particles smaller than 2 to 3 µm have a chance of reaching the lungs.
The Microorganism’s Perspective
As previously discussed, microorganisms that inhabit many surfaces of the human body (see Figure 3-5) are referred to as colonizers, or normal flora (also referred to as normal microbiota). Some are transient colonizers, because they are able to survive, but do not multiply, on the surface and are frequently shed with the host cells. Others, called resident flora, not only survive but also thrive and multiply; their presence is more persistent.
Knowledge of the normal flora of the human body is extremely important in diagnostic microbiology, especially for determining the clinical significance of microorganisms isolated from patient specimens. Organisms considered normal flora are frequently found in clinical specimens. This may be a result of contamination of normally sterile specimens during the collection process or because the colonizing organism is actually involved in the infection. Microorganisms considered as normal colonizers of the human body and the anatomic locations they colonize are addressed in Part VII.
Microbial Colonization
Colonization may be the last step in the establishment of a long-lasting, mutually beneficial (i.e., commensal), or harmless, relationship between a colonizer and the human host. Alternatively, colonization may be the first step in the process for the development of infection and disease. Whether colonization results in a harmless or damaging infection depends on the characteristics of the host and the microorganism. In either case, successful initial colonization depends on the microorganism’s ability to survive the conditions first encountered on the host surface (Box 3-2).
To avoid the dryness of the skin, organisms often seek moist areas of the body, including hair follicles, sebaceous (oil, referred to as sebum) and sweat glands, skin folds, underarms, the genitals or anus, the face, the scalp, and areas around the mouth. Microbial penetration of mucosal surfaces is mediated by the organism becoming embedded in food particles to survive oral and gastrointestinal conditions or contained within airborne particles to aid survival in the respiratory tract. Microorganisms also exhibit metabolic capabilities that assist in their survival. For example, the ability of staphylococci to thrive in relatively high salt concentrations enhances their survival in and among the sweat glands of the skin.
Besides surviving the host’s physical and chemical conditions, colonization also requires that microorganisms attach and adhere to host surfaces (see Box 3-2). This can be particularly challenging in places such as the mouth and bowel, in which the surfaces are frequently washed with passing fluids. Pili, the rodlike projections of bacterial envelopes, various molecules (e.g., adherence proteins and adhesins), and biochemical complexes (e.g., biofilm) work together to enhance attachment of microorganisms to the host cell surface. Biofilm is discussed in more detail later in this chapter. (For more information concerning the structure and functions of pili, see Chapter 2.)
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