we explored the human–microbe relationship, with emphasis on the role of microorganisms in disease. In this chapter, we examine the other side of the relationship—that of the host de fending itself against microorganisms. As previously stated, in light of the unrelenting microbial contact with and colonization of hu mans, it is something of a miracle that we are not constantly infected and diseased. Our ability to overcome this continual assault on our bodies is the result of a fascinating, highly complex system.
To protect the body against pathogens, the immune system re lies on an overlapping network of host defenses that operate on several levels. These include innate, natural defenses present at birth that provide nonspecific resistance to infection and adaptive immunities that are specific and must be acquired. These levels of protection are sometimes divided into categories called the first, second, and third lines of defense (table 1).
Table1. General Features of Host Defenses
The first line of defense includes any barrier that blocks invasion at the portal of entry. This mostly nonspecific line of defense limits access to the internal tissues of the body. However, it is not considered a true immune response because it does not involve recognition of a specific foreign substance and is very general in its actions.
The second line of defense is a more internalized system of protective cells and fluids, which includes inflammation and phagocytosis. It acts rapidly at both the local and systemic levels once the first line of defense has been circumvented, and in most reactions it is also nonspecific.
The highly specific third line of defense is adaptive and ac quired on an individual basis as each foreign substance is encountered by white blood cells called lymphocytes. Responses directed toward each different microbe produce unique protective substances and memory cells that can come into play if that microbe is encountered again.
The various levels of defense do not operate in a completely separate fashion; most defenses overlap and are even redundant in some of their effects. This cooperative reaction targets invading microbes on several different fronts simultaneously, making their survival unlikely. To present the interactive nature of host defenses, we start with basic concepts that will build a foundation for understanding the more complex reactions of the immune system to come later.
Barriers at the Portal of Entry: An Inborn First Line of Defense
A number of defenses are a normal part of the body’s anatomy and physiology. These inborn, nonspecific defenses can be divided into physical, chemical, and genetic barriers that impede the entry of not only microbes but any foreign agent, whether living or not (figure 1).
Fig1. Defenses. Some nonspecific defense barriers that help prevent entry of microorganisms into the host’s tissues.
Physical or Anatomical Barriers at the Body’s Surface
The skin and mucous membranes of the respiratory and digestive tracts have several built-in defenses. The outermost layer (stratum corneum) of the skin is composed of epithelial cells that have become compacted, cemented together, and impregnated with an in soluble protein, keratin. The result is a thick, tough layer that is impervious and waterproof. Few pathogens can penetrate this un broken barrier, especially in regions such as the soles of the feet or the palms of the hands, where the stratum corneum is much thicker than on other parts of the body. Other cutaneous barriers include hair follicles and skin glands. The hair shaft is periodically extruded, and the follicle cells are desquamated, or shed. The flushing effect of sweat glands also helps remove microbes.
The mucocutaneous membranes of the digestive, urinary, and respiratory tracts and of the eye are moist and permeable. Despite the normal wear and tear upon these epithelia, damaged cells are rapidly replaced. The mucous coat on the free surface of some membranes impedes the entry and attachment of bacteria. Blinking and tear production (lacrimation) flush the eye’s surface with tears and rid it of irritants. The constant flow of saliva helps carry microbes into the harsh conditions of the stomach. Vomiting and defecation also evacuate noxious substances or microorganisms from the body.
The respiratory tract is constantly guarded from infection by elaborate and highly effective adaptations. Nasal hair traps larger particles. Rhinitis, the inflammation of the nasal mucosa often seen with allergy and colds, creates a copious flow of mucus and fluids that helps to flush out the nasal passageways. In the respiratory tree (primarily the trachea and bronchi), a ciliated epithelium (called the ciliary escalator) conveys foreign particles entrapped in mucus toward the pharynx to be removed (figure 2). Irritation of the nasal passage reflexively initiates a sneeze, which expels a large volume of air at high velocity. Similarly, the acute sensitivity of the bronchi, trachea, and larynx to foreign matter triggers coughing, which ejects irritants.
Fig2. The ciliary defense of the respiratory tree. Epithelial cells in the trachea are covered in tufts of cilia that sweep mucus, filled with small particles and microbes, up and away from the lungs. Science Photo Library/Alamy Stock Photo
The genitourinary tract derives partial protection from the continuous trickle of urine through the ureters and from periodic bladder emptying that flushes the urethra.
Even though the normal microbial residents do not constitute a physical or anatomical barrier, their presence can block the access of pathogens to epithelial surfaces. They may also compete with pathogens for limited resources or alter the environment of the body, making it less welcoming for pathogens. Some bacterial residents of the large intestine, for instance, secrete bacteriocins or antibiotics, which can inhibit or kill other bacteria.
Nonspecific Chemical Defenses
The skin and mucous membranes offer a variety of chemical defenses. Sebaceous secretions exert an antimicrobial effect, and specialized glands such as the meibomian glands of the eyelids lubricate the conjunctiva with an antimicrobial secretion. Other defenses in tears and saliva include lysozyme and defensins. Lysozyme is an enzyme that hydrolyzes the peptidoglycan in the cell wall of bacteria. Defensins are peptides produced by various cells and tissues that damage cell membranes and lyse bacteria and fungi. Skin cells produce a defensin called dermicidin that helps eliminate bacteria, and paneth cells in the intestine secrete defensins that can destroy or inhibit several types of infectious agents. The high concentrations of lactic acid and electrolytes in sweat and the skin’s acidic pH and fatty acid content are also inhibitory to many microbes.
Internally, the hydrochloric acid content of the stomach renders protection against many pathogens that are swallowed. The intestine’s digestive juices and bile are also potentially destructive to microbes. Even semen contains an antimicrobial chemical that inhibits bacteria, and the vagina has a protective acidic pH maintained by lactobacilli that are part of the microbiota.
Genetic Resistance to Infection In certain cases, the genetic makeup of an individual is different enough to ensure protection from some pathogens. One explanation for this phenomenon is that some pathogens have such great specificity for one host species that they are incapable of infecting other species. This specificity is particularly true of viruses, which can invade only by at taching to a specific host receptor. Newcastle virus may kill your parrot while you remain safe, and it is perfectly okay to cuddle with your dog while recovering from the mumps. Both viruses have a limited host range. But this defense does not hold true for zoonotic infectious agents that attack a broad spectrum of animals. Genetic differences in suscep tibility can also exist within members of one species. Humans carrying a mutation responsible for sickle-cell disease are resistant to malaria. Genetic differences also exist in susceptibility to tuberculosis, Hansen’s disease (leprosy), and certain systemic fungal infections.
The vital contribution of barriers is clearly demonstrated in people who have lost them or never had them. Patients with severe skin damage due to burns are extremely susceptible to infections; those with blockages in the salivary glands, tear ducts, intestine, and urinary tract are also at greater risk for infection. But as important as it is, the first line of defense alone cannot provide adequate protection. Because many pathogens find a way to circumvent the barriers by using their virulence factors, a whole new set of defenses—inflammation, phagocytosis, specific immune responses—is ready to react to them.
