Natural Killer Cells

Natural Killer (NK) cells are yet another type of lethal lymphocyte. Like cytotoxic T cells, they contain granules filled with potent chemicals. They are called "natural" killers because they, unlike cytotoxic T cells, do not need to recognize a specific antigen before swinging into action. They target tumor cells and protect against a wide variety of infectious microbes. In several immunodeficiency diseases, including AIDS, natural killer cell function is abnormal. Natural killer cells may also contribute to immunoregulation by secreting high levels of influential lymphokines.

Both cytotoxic T cells and natural killer cells kill on contact. The killer binds to its target, aims its weapons, and then delivers a lethal burst of chemicals that produces holes in the target cell's membrane. Fluids seep in and leak out, and the cell bursts.

 

Phagocytes, Granulocytes, and Their Relatives

Phagocytes (literally, "cell eaters") are large white cells that can engulf and digest marauding microorganisms and other antigenic particles. Some phagocytes also have the ability to present antigen to lymphocytes.

Important phagocytes are monocytes and macrophages. Monocytes circulate in the blood, then migrate into tissues where they develop into macrophages ("big eaters"). Macrophages are seeded throughout body tissues in a variety of guises. Specialized macrophages include alveolar macrophages in the lungs, mesangial phagocytes in the kidneys, microglial cells in the brain, and Kupffer cells in the liver.

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Human Macrophage Ingesting Candida Albicans QuickTime 508 K

Macrophages are versatile cells that play many roles. As scavengers, they rid the body of worn-out cells and other debris. Foremost among the cells that "present" antigen to T cells, having first digested and processed it, macrophages play a crucial role in initiating the immune response. As secretory cells, monocytes and macrophages are vital to the regulation of immune responses and the development of inflammation; they churn out an amazing array of powerful chemical substances (monokines) including enzymes, complement proteins, and regulatory factors such as interleukin-1. At the same time, they carry receptors for lymphokines that allow them to be "activated" into single-minded pursuit of microbes and tumor cells.

Macrophages are not the only cells to present antigen to lymphocytes. Other antigen-presenting cells include B cells, as noted above, and dendritic cells, irregularly shaped white blood cells found in the spleen and other lymphoid organs. Dendritic cells typically have long threadlike tentacles that enmesh lymphocytes and antigens. Langerhans cells are dendritic cells that travel about in the skin, picking up antigen and transporting it to nearby lymph nodes. Many other types of body cells, properly stimulated, can also be recruited to present antigens to lymphocytes.

Another critical phagocyte is the neutrophil. Neutrophils are not only phagocytes but also granulocytes: they contain granules filled with potent chemicals. These chemicals, in addition to destroying microorganisms, play a key role in acute inflammatory reactions.

Also known as polymorphonuclear leukocytes or polymorphs (because their nuclei come in "many shapes"), granulocytes include eosinophils and basophils as well as neutrophils. (The cells are named for the way they stain in the laboratory: eosinophils, for instance, have an affinity for acidic dyes such as eosin.) The phagocytic neutrophil uses its prepackaged chemicals to degrade the microbes it ingests; eosinophils and basophils typically "degranulate," releasing their chemicals to work on cells or microbes in their surroundings.

The mast cell is a noncirculating counterpart of the basophil. Located in the lungs, skin, tongue, and linings of the nose and intestinal tract, the mast cell is responsible for the symptoms of allergy (Allergy).

Another related structure is the blood platelet. Platelets, too, contain granules. In addition to promoting blood clotting and wound repair, platelets release substances that activate components of the immune system.

Complement

The complement system is made up of a series of about 25 proteins that work to "complement" the activity of antibodies in destroying bacteria, either by facilitating phagocytosis or by puncturing the bacterial cell membrane. Complement also helps to rid the body of antigen-antibody complexes. In carrying out these tasks, it induces an inflammatory response.

Complement proteins circulate in the blood in an inactive form. When the first of the complement substances is triggered-usually by antibody interlocked with an antigen-it sets in motion ripple effect. As each component is activated in turn, it acts upon the next in a precise sequence of carefully regulated steps known as the "complement cascade."

In the so-called "classical" pathway of complement activation, a series of proteins gives rise to a complex enzyme capable of cleaving a key protein, C3. In the "alternative" pathway-which can be triggered by suitable targets in the absence of antibody-C3 interacts with a different set of factors and enzymes. But both pathways end in creation of a unit known as the membrane attack complex. Inserted in the wall of the target cell, the membrane attack complex constitutes a channel that allows fluids and molecules to flow in and out. The target cell rapidly swells and bursts.

Meanwhile, various fragments flung off during the course of the cascade can produce other consequences. One byproduct causes mast cells and basophils to release their contents, producing the redness, warmth, and swelling of the inflammatory response. Another stimulates and attract neutrophils. Yet another, C3b, opsonizes or coats target cells so as to make them more palatable to phagocytes, which carry a special receptor for C3b.

The C3b fragment also appears to play a major role in the body's control of immune complexes. By opsonizing antigen-antibody complexes, C3b helps prevent the formation of large and insoluble (and thus potentially damaging) immune aggregates. Moreover, receptors for C3b are also present on red blood cells, which appear to use the receptors to pick up complement-coated immune complexes and deliver them to the Kupffer cells in the liver.

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