The Innate Immune Response

Rose Rosetattle Causal Organism

Once microorganisms were shown to cause disease, scientists worked to explain how the body defended itself against invasion by microorganisms. Elie Metchnikoff, a Russian-born scientist, theorized that there were specialized cells within the body that could destroy invading organisms. His ideas arose from observations he made while studying the transparent immature larval form of starfish in Sicily in 1882. As he looked at the larvae in the microscope, he could see ameba-like cells within the bodies. He described his observations:

.. . I was observing the activity of the motile cells of a transparent larva, when a new thought suddenly dawned on me. It occurred to me that similar cells must function to protect the organism against harmful intruders .. . . I thought that if my guess was correct a splinter introduced into the larva of a starfish should soon be surrounded by motile cells much as can be observed in a man with a splinter in his finger. No sooner said than done. In the small garden of our home .. . I took several rose thorns that I immediately introduced under the skin of some beautiful starfish larvae which were as transparent as water. Very nervous, I did not sleep during the night, as I was waiting for the results of my experiment. The next morning, very early, I found with joy that it had been successful.

Metchnikoff reasoned that certain cells present in animals were responsible for ingesting and destroying foreign material. He called these cells phagocytes, meaning "cells that eat," and he proposed that these cells were primarily responsible for the body's ability to destroy invading microorganisms.

When Metchnikoff returned to Russia, he looked for a way to study the ingestion of materials by phagocytes, called phagocytosis. A water flea that could be infected with a yeast provided a vehicle for such studies. He observed phagocytes ingesting and destroying invading yeast cells within the experimentally infected, transparent water fleas. In 1884, Metchnikoff published a paper that strongly supported his contention that phagocytic cells were primarily responsible for destroying disease-causing organisms. He spent the rest of his life studying phagocytosis and other biological phenomena; in 1908, he was awarded the Nobel Prize for these studies of immunity.

—A Glimpse of History

FROM A MICROORGANISM'S STANDPOINT, THE tissues and fluids of the human body are much like a warm culture flask filled with a nutrient-rich solution. Considering this, it may be surprising that the interior of the body—including blood, muscles, bones, and organs—is generally sterile. If this were not the case, microbes would simply degrade our tissues, just as they readily decompose the carcass of a dead animal.

How does the interior of the body remain sterile in this world full of microbes? Like other multicellular organisms,

372 Chapter 15 The Innate Immune Response humans have evolved several mechanisms of defense. First, we are covered with skin and mucous membranes that prevent entry of most foreign material, including microbes, into the body. Ready in case the barriers are breached are sensor systems that detect molecules associated with danger; for example, compounds that are unique to bacteria or are typically released only when tissues are damaged. These sensors can direct and assist other host defenses, facilitating the destruction of the foreign material. Also lying in wait are host cells that specialize in ingesting and digesting foreign material; if needed, additional reinforcements can be recruited to the site of breach. The protection provided by these systems is termed innate immunity, reflecting that we are born with it. Innate immunity differs from adaptive immunity, which will be described shortly, in that all invaders are dealt with using a limited set of weapons. Although the number of copies of the various weapons can be modulated in response to an invader, their mechanisms cannot be modified to enhance the reaction.

The components of innate immunity have been called non-specific defenses, but recent discoveries have shown that most of these components are far from unfocused; instead, they rely on the recognition of certain molecular patterns associated with invading microbes or tissue damage, a feature referred to as pattern recognition. Molecular patterns associated with pathogens include various compounds unique to bacterial cell walls, such as lipopolysaccharide, lipoteichoic acid, and peptidoglycan, and other molecules. Those associated with damage include various proteins that are normally intracellular and are now outside cells, and substances produced during tissue necrosis and damage. ■ lipopolysaccharide, p. 59 ■ lipoteichoic acid, p. 59 ■ peptidoglycan, p. 58

In addition to innate immunity, vertebrates have evolved a more specialized response, termed the adaptive immune response; this develops throughout life and substantially increases the ability of the host to defend itself. Each time the body is exposed to foreign material, the adaptive defense system first "learns" and then "remembers" the most effective response to that specific material; it then reacts accordingly if the material is encountered again. The foreign material to which the immune system responds is called an antigen. On first exposure to an invading microbe or other antigen, the response develops relatively slowly, during which time the microbe may cause damage if the innate defenses are unable to contain it. Successive exposures, however, lead to a swift and greater repeat response, generally eliminating the invader before it causes obvious harm.

There are two general mechanisms used by the adaptive immune response to eliminate an invader. If the antigen is within one of the body's own cells, which are referred to as either a host cell or a "self" cell, then the cell may be sacrificed as a means of destroying the invader. If the antigen is extracellular, then the body responds by making antibodies. These glycopro-tein molecules have two functional regions; one region binds specifically to the antigen and the other functions as a "red flag," directing other host defenses to remove or destroy the antigen.

The study of the many mechanisms the body uses to defend itself against invading microbes is called immunology.

It encompasses not only the study of protection against infectious agents, but also cancers and the acceptance or rejection of transplanted cells and organs. Immunologists also study the effects of the immune response that can damage the body, such as autoimmunity, which occurs when the immune response is inappropriately directed against the cells of one's own body, and hypersensitivity, or allergic reactions.

To simplify the description of a network as complex and intricate as the immune system, it is helpful to consider it as a series of individual parts. This chapter, for example, will focus almost exclusively on innate immunity. Bear in mind, however, that although the various parts are discussed separately, in the body their actions are intimately connected and coordinated. In fact, as you will see in chapter 16, certain components of the innate defenses are instrumental in educating the adaptive defenses, helping them to distinguish antigens that represent danger.

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