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The innate immune system is composed of physical barriers, cells, and circulating factors that are always active and ready to repel microbes. They form a boundary between your tissues and the vast majority of viruses, bacteria, and fungi that live on and inside you. Innate immune cells are also important for cleaning up debris from dying cells and repairing damaged tissues.

In this chapter, we will discuss the mechanisms of innate immunity, including their role in host defense and in driving inflammation. Unlike the lymphocytes that make up the adaptive immune system, which can be tuned to sense and respond in different ways to different infections, components of the innate immune system have a limited number of ways to sense and respond to infections. However, the advantage of the innate immune system is that it responds rapidly and targets molecular patterns that are widely shared among microbes.


An extremely important, but often overlooked, component of host defense is the barrier formed by skin and mucous membranes. The epithelia covering our skin, respiratory, gastrointestinal, and genitourinary tracts provide the first line of defense against microbes in the external world. This occurs through a combination of mechanical, chemical, and biological means. The central mission of the barrier is to separate the outside world from the host, allowing various microbes to survive in niches along the surface, but preventing any from gaining a foothold where they could invade. As we will discuss later, breach of the barrier causes activation of local and systemic innate inflammation, followed by recruitment of adaptive immunity.

Mechanical Barrier

The outermost layer of the barrier is formed by epithelial cells, connected to one another by tight junctions. The skin’s epidermis is covered by a layer of keratinized squamous cells that are continuously shed (“desquamated”). Along with sweat secretion, this limits the ability of microorganisms to attach and invade. Similarly, nonskin barriers are called mucous membranes because they are coated by mucins, a sticky mixture of glycoproteins produced by secretory epithelial cells of the respiratory, gastrointestinal, and genitourinary tracts. Mucus makes these surfaces more difficult to adhere to and penetrate.

The cells of mucous membranes also undergo rapid division, sloughing off continuously, and the ciliated cells lining the respiratory tract, the gastrointestinal tract’s peristalsis, and the continuous flow of urine from the kidney through the bladder and urethra ensure that microbes cannot attach and invade these sites. Failure of any of these mechanisms is a common cause of infection due to bacteria or fungi that otherwise colonize us harmlessly. In patients with severe skin burns, patients with pulmonary ciliary cell disorders, and patients with bowel or urinary obstruction, infection is the key cause of morbidity and mortality.

Chemical Barrier

Epithelial cells also produce a number of chemicals and ...

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