The immune system: mechanisms that counteract disease

Alcohol Health & Research World,  Wntr, 1992  by Charles J. Grossman,  Eve J. Wilson

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The body is protected from infectious disease and cancer by an extraordinarily complex, intricately regulated, and highly efficient network of cellular and biochemical activities.

Survival depends on the body's ability to perceive and respond to a variety of signals, detected through the five senses--taste, touch, sight, smell, and hearing. Survival also depends on the body's ability to perceive and respond to potential pathogens. For this purpose, the immune system operates as a kind of sixth sense that detects and protects the body from foreign substances and infectious micro-organisms.

In humans and other vertebrates, both nonspecific and specific defense mechanisms confer immunity from disease. Nonspecific immunity, sometimes called innate immunity, consists of those barriers, substances, and cells that act as a first line of defense against infection: these mechanisms prevent most potential pathogens from establishing overt disease. If nonspecific mechanisms are overcome, specific immune defenses are called into action. Specific immunity is described as such because the mechanisms conferring protection require specific recognition of infectious or foreign agents, via receptors on specialized cells called B- and T-lymphocytes, or B- and T- cells. Specific immunity may also be referred to as acquired or adaptive immunity, because once the immune system has "seen" (or been sentized to) a particular pathogen, special mechanisms are triggered to ensure that re-exposure to that pathogen will not result in disease.

The orchestrated efforts of nonspecific and specific immune responses provide a highly effective shield against microbes and foreign or cancerous cells that otherwise would disrupt homeostasis(1) and lead to disease. This overview explains many of the key cell types, regulatory substances, and interactive mechanisms that make up the normal immune system. Some attention also is given to the consequences of abnormal or inefficient immune function. Whereever possible, this review presents basic concepts before approaching the more intricate interactions that constitute immune responses.

NONSPECIFIC IMMUNE DEFENSES

Nonspecific immune defenses bear the brunt of microbial assault, effectively preventing many disease-causing organisms from entering or spreading infection throughout the body. Nonspecific defenses include the barriers provided by intact skin and mucosal surfaces, a variety of cellular activities, inflammatory reactions, and cell-killing or inhibitory factors produced and released in response to infection.

Mechanical Barriers

So long as they remain intact, the skin and mucosal membranes provide a mechanical barrier that prevents the entry of infectious agents and harmful substances into the body. In addition, the skin's sweat glands and sebaceous glands secrete substances that are toxic to many types of bacteria. Mucus secreted by membranes of the respiratory, urinary, digestive, and reproductive tracts creates a protective lining that can trap foreign particles and microorganisms. Cells lining the stomach secrete hydrochloric acid, which can inactivate or kill ingested microorganisms. Body fluids such as tears and saliva contain lysozyme, an enzyme capable of killing bacteria by disrupting their cell walls.

Nonspecific Cellular Defenses

Microbes that penetrate the skin and mucous membranes and enter the under-lying tissue are confronted by phagocytes, cells that literally consume the foreign organisms or substances in a process known as phagocytosis (phago is from the Greek word phagein, to eat). Macrophages, cells found in tissues and organs throughout the body, are chief among a number of phagocytic cell types. Macrophages develop from cells known as monocytes that originate in the bone marrow and circulate in the blood. Contact with bacterial components or other substances stimulates monocytes and macrophages to differentiate into "angry macrophages" with highly effective cell-killing and phagocytic properties. Neutrophils, found in blood and tissues, are another type of phagocytic cell. Within neutrophils and macrophages, powerful degradative enzymes and toxic oxygen-containing compounds such as hypochlorite and hydrogen peroxide serve to destroy phagocytosed microorganisms.

Natural killer, or NK cells, found in blood and in various immune system organs and tissues, are thought to provide an important nonspecific cellular defense against cancer cells and virus-infected cells. NK cells can directly bind to and kill cancerous cells and cells infected by a variety of different viruses. The mechanisms by which NK cells recognize and destroy their targets are not completely understood.

Inflammation

Inflammatory responses are triggered by tissue injury. Among the first changes following injury is an increased permeability of local blood vessels, facilitating blood flow and the entry of blood proteins and phagocytes into the area. Specialized inflammatory cells (phagocytes, basophils, and mast cells) and injured tissue cells release such chemical mediators of inflammation as histamine, proteins making up the complement system (see discussion below), prostaglandins, and clotting proteins. All of these substances help to increase blood vessel permeability; some serve to attract still more phagocytic cells to the area, for assistance in eliminating any foreign or infectious substances that may have been introduced. Clotting proteins generated by inflammatory and other cells help to wall off the injured area, preventing the spread of harmful agents to surrounding tissues. If infectious microorganisms are introduced, the complement system is activated, as detailed below, and specific immune mechanisms become involved.