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Most organisms and foreign substances cannot penetrate intact epithelial layers that insulate the body’s interior from pathogens in the environment (Figure 3.1). These epithelial layers include the skin and the tissue surfaces located at body openings: the respiratory, gastrointestinal and urogenital tracts, and the ducts of secretory glands (salivary, lacrimal, and mammary glands). These anatomical barriers also contribute to the physical and mechanical mechanisms of innate defense against pathogens (e.g., eye blinking, coughing, sneezing, directional flow of fluids to the stomach and intestine). In addition, epithelial cells at these and other anatomical sites generate active chemical and biochemical defenses by producing and deploying antimicrobial peptides and proteins.

Figure 3.1. Skin and other epithelial barriers to infection. In addition to serving as physical barriers, the skin and mucosal and glandular epithelial layers are protected from microbial colonization mechanically (cilia, fluid flow, smooth muscle contraction), chemically (pH, antimicrobial peptides, enzymes) and through cellular innate defense mechanisms (dendritic cells, macrophages).

Some microorganisms can enter through sebaceous glands and hair follicles. However, the acid pH of sweat and sebaceous secretions and the presence of various fatty acids and hydrolytic enzymes (e.g., lysozymes) all have some antimicrobial effects, therefore minimizing the importance of this route of infection. In addition, soluble proteins, including the interferons (see Chapter 11) and certain members of the complement system (see Chapter 4) found in the serum, contribute to nonspecific immunity. Interferons are a group of proteins made by cells in response to viral infection, which essentially induces a generalized antiviral state in surrounding cells. Activation of complement components in response to certain microorganisms results in a controlled enzymatic cascade, which targets the membrane of pathogenic organisms and leads to their destruction.

An important innate immune mechanism involved in the protection of many areas of the body, including the respiratory and gastrointestinal tracts, involves the simple fact that surfaces in these areas are covered with mucus. In these areas, the mucous membrane barrier traps microorganisms, which are then swept away by ciliated epithelial cells toward the external openings. The hairs in the nostrils and the cough reflex are also helpful in preventing organisms from infecting the respiratory tract.

The elimination of microorganisms from the respiratory tract is aided by pulmonary or alveolar macrophages, which, as we shall see later, are phagocytic cells able to engulf and destroy some microorganisms. Similarly, phagocytic cells called microglial cells provide innate immune defense within the central nervous system. Microorganisms that have penetrated the mucous membrane barrier can be phagocytized by macrophages or otherwise transported to lymph nodes, where many are destroyed. The environment of the gastrointestinal tract is made hostile to many microorganisms by other innate mechanisms, including the hydrolytic enzymes in saliva, the low pH of the stomach, and the proteolytic enzymes and bile in the small intestine. The low pH of the vagina serves a similar function.

Once an invading microorganism has penetrated the various physical and chemical barriers, the next line of defense consists of various specialized innate immune cells whose purpose is to destroy the invader. These include the phagocytic macrophages and tissue mast cells in addition to polymorphonuclear leukocytes (neutrophils, eosinophils, and basophils). Each of these cell types is derived from myeloid precursors found in the bone marrow (see Figure 1.1). As we shall see later in this chapter, other innate immune cells contribute to the generation of cell‐ and cytokine‐mediated innate defense mechanisms when pathogens manage to evade physical and chemical defense barriers. In some cases, activated macrophages and neutrophils participating in early innate defense events that culminate in enhanced phagocytosis and an oxidative burst have the ability to eliminate pathogens without evoking an adaptive immune response mediated by B and T cells. More commonly, the innate immune response to pathogens leads to subsequent activation of antigen‐specific lymphocytes responsible for long‐lasting memory responses. The collaborative nature of cells involved in innate immune responses underscores the important interrelationship of these two arms of our immune system.

A classic example of the functional interrelationship between the innate and adaptive immune systems is illustrated by the roles played by antigen‐presenting cells (APCs). As their name implies, APCs present antigens (e.g., pieces of phagocytized bacteria) to T cells within the adaptive immune system. T cells must interact with APCs that display antigens for which they are specific in order for the T cells to be activated to generate antigen‐specific responses. Thus, while the title of this section implies that the cells described below are principally involved in innate immune responses, it is essential to recognize their important role in adaptive immune responses at this early stage of study of the immune system.