Sci. Aging Knowl. Environ., 11 June 2003
Vol. 2003, Issue 23, p. oa1
[DOI: 10.1126/sageke.2003.23.oa1]


Immunity Challenge

Deciphering how the immune system changes with age might reveal ways to bolster resistance to infection and cool inflammation in the elderly

R. John Davenport;2003/23/oa1

Abstract: As people get older, their immune systems falter. The elderly are more susceptible to infections than youngsters are, and hyperactive inflammatory responses appear to contribute to some age-associated illnesses, including Alzheimer's disease and atherosclerosis. Investigating the effect of aging on the immune system was once a scientific stepchild, but card-carrying immunologists are now tackling the problem head-on. Despite the immune system's complexity, researchers have started to make sense of how its components change with age. As the research progresses, scientists hope to bolster elderly people's response to infectious diseases and quiet the inflammation that can make aging a painful experience.

A young watchdog repels trespassers and protects the junkyard. But with time, the beast loses its bite: Its fading vision and arthritic hips let encroachers sneak in. And the cur's remaining ferocity is misdirected, snapping at anything within range--including its owner. A body's sentinel ages awkwardly, too. Young immune systems identify potentially harmful invaders and defuse the threat before illness ensues. But with age the immune system loses its power to recognize and fight off new interlopers. At the same time, it exists in a state of constant agitation and ignites chronic inflammation. The health consequences are dire: Pneumonia and influenza are among the top five causes of death for people age 65 or older, diseases that most young people rebuff successfully--and the tissue breakdown that arises from sustained inflammation fosters age-related diseases such as atherosclerosis and Alzheimer's disease.

Interventions that restore youthful immunity in older individuals are just a twinkle in scientists' eyes, but prospects are brightening as a more complete picture of how immunity changes with age emerges. In the past, that question was entertained primarily by researchers studying aging and was shunned by immunologists. The U.S. National Institute on Aging convened a meeting on aging and immunology for the first time in 1997. It brought together immunologists and gerontologists, but "each group didn't know what the other was talking about," says immunologist Donna Murasko of Drexel University in Philadelphia. The situation has since changed. In the second meeting, which took place in June 2002, "there was a real line of communication between the two groups," she says. And as the study of the aging immune system matures, it is revealing finer details of the process. For decades, "people described changes with aging," says immunologist Rita Effros of the University of California, Los Angeles, "but they didn't scratch the surface of mechanism." Now, researchers are beginning to dig into that area.

The Lineup Back to Top

Getting too close to someone with the sniffles, eating sushi that isn't fresh, or allowing dirt into an open wound exposes a person to disease-causing viruses and microorganisms. To fend off the invaders, the body calls an arsenal of specialized organs, cells, and molecules into action.

Cells that constitute the innate immune system respond first. They recognize molecular patterns on pathogens that betray the interlopers as foreign objects. The host cells engulf and destroys the intruders. Innate immune cells and other cells at the site of infection release a variety of immune system-spurring molecules. These signals spark a response that brings blood into the tissue to step up the defense--resulting in the swelling and redness that mark inflammation.

Sometimes the innate response is enough to obliterate the threat. But if the infection persists, a more targeted defense kicks in. The body recruits cells from the adaptive immune system that recognize the particular trespasser.

B cells and T cells--two types of lymphocytes--do the grunt work of the adaptive immune system. They produce proteins that bind to molecular bits that identify a pathogen; these bits are known as antigens. B cells--so named because they mature from stem cells in the bone marrow--produce and discharge antibodies, which roam the bloodstream. Each B cell manufactures only one type of antibody, but a body's collection of B cells generates an array of antibodies, each recognizing subtly different targets. If one of those antibodies matches part of an infiltrator, the antibody binds to it and instigates a process that destroys the invader.

As B cells churn out fine-tuned antibodies, T cells--which get their training in the thymus, a small gland behind the breastbone--participate in a second kind of adaptive immune response, cell-mediated immunity. This arm of the adaptive immune response relies on T cell receptors (TCRs), proteins that sit on the surface of T cells. The body's panoply of T cells, each with a unique flavor of TCR, seeks out host cells that have been invaded. Such host cells display on their surface antigens belonging to the infective agent; a matching TCR glues the T cell to the infected host cell and sets in motion processes that kill the cell--and its contents--sacrificing it for the good of the organism. In addition to these cytotoxic T cells, another type--helper T cells--supports B cells and cytotoxic T cells by binding to them and releasing proteins called cytokines, which attract immune cells and spur them to divide.

The presence of an antigen stimulates the growth and division of those T cells and B cells that are tuned to it. Thus, the body makes more of the cells that can best defend against a particular threat. These cells can morph into either effector cells, which are active immune cells, or memory cells, which are dormant but remain poised to jump into action should a second infection hit. Memory cells respond much faster to an antigen than do naive cells that have never bound to an antigen. This quick reaction underlies the benefit of vaccines, which expose an organism to a pathogen's molecular patterns, prompting the duplication of particular T and B cells. The vaccinated individual is thus prepared to fight a future infection by that specific invader.

The immune system's complexity makes studying it as daunting as following the characters and plot twists of a Russian novel. But scientists have devised ways to track some of the main players. After isolating immune cells from human or animal subjects, researchers employ antibodies that recognize specific proteins on the surface of the cells to discern their type. For instance, helper T cells carry the CD4 surface protein, whereas memory cells display the CD8 surface protein; the two cell types are known as CD4+ T cells and CD8+ T cells, respectively. Other markers further subdivide those groups into naive and memory cells. By examining the number and type of immune cells from organisms of different ages or genetic makeups and by studying the cells' behavior in culture, researchers can probe how the immune system shifts with age.

Aging to a T Back to Top

Such studies don't always produce conclusive results. Scientists have tracked age-dependent changes in many different cell populations, but discrepancies frequently arise among research teams. For instance, some studies have found that the ratio of CD4+ to CD8+ increases with age, some have found that it decreases, and others have found no change. One problem, says immunologist Beatrix Grubeck-Loebenstein of the Institute for Biomedical Aging Research in Innsbruck, Austria, is that old animals--and their immune cells--often have varied histories. Immune system components are likely affected by numerous factors--such as diet, genetics, and health--in addition to chronological age. As a consequence, differences in immune function among individuals increases with age, obscuring age-related trends.

Nevertheless, some clear patterns have emerged. Both rodent and human T cell populations undergo a shift from mostly naive T cells in young adults to mostly memory T cells in older individuals. In part, this transformation reflects lifelong exposure to a spectrum of infectious agents, all of which stimulate naive cells to become memory cells. In addition, the thymus pumps out fewer new naive T cells with age (although the thymus remains more active than once thought; see "Talkin' About an Involution" below). Furthermore, mice with relatively few memory cells and relatively many naive cells tend to live longer than others of the same chronological age, according to work by gerontologist Richard Miller of the University of Michigan, Ann Arbor, and colleagues (1; see Miller Perspective). That work suggests that tracking naive T cells might help gauge physiological age.

In addition, older organisms often are overrun by memory cells that carry a single type of TCR. These so-called clonal expansions arise when a single T cell divides more rapidly than the average T cell. Its clones eventually make up a large percentage of the total number of T cells. Thus, the memory cells from an old animal might recognize a limited set of antigens despite being plentiful in number. Many of the clonal expansions crowding an elderly person's immune system result from previous infections by so-called latent viruses. These viruses infect their hosts and remain dormant in the cells throughout an animal's life. For instance, cytomegalovirus colonizes approximately half the human population; the virus is usually harmless, but it can kill or incapacitate individuals with flagging immune systems. Some studies suggest that these latent infections can sop up immune capacity, increasing the difficulty of fighting off other infections. Older humans with cytomegalovirus harbor 33% more clonal expansions of memory T cells, some aimed at cytomegalovirus and some not, than do uninfected individuals, according to work published in the August 2002 Journal of Immunology (2; see "T Cell Tunnel Vision").

Despite an apparent surplus of memory cells, older animals are not necessarily more able to fight off the pathogens that those cells recognize. Memory T cells usually carry the CD28 surface protein, which helps stimulate the cells to divide when antigen is present. But old memory cells tend to lose CD28 and, as a result, multiply less robustly when exposed to antigen than do younger cells.

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Sorting it out. Researchers pigeonhole immune cells by identifying proteins that appear on their surfaces. Young individuals (left) carry predominantly naive T cells (green), identified by the CD45RA and the CD28 proteins. Older individuals (right) lose this batch of pliable cells and accumulate memory (red) and effector (blue) T cells, rendering the host more susceptible to new infections. [Credit: Beatrix Grubeck-Loebenstein/Institute for Biomedical Aging Research]

Studies on humans support the idea that memory cells eventually forget their earlier valor. Elderly people who do not produce antibodies after receiving a flu vaccine carry more memory T cells that lack CD28 than do those who respond well to the vaccine, according to work published last year by Grubeck-Loebenstein and colleagues (3). Together, these results suggest that a lifetime of infections narrows an individual's ability to mount defenses against new pathogens and to develop immunity through vaccination.

Other immune system behaviors also shift with age. Old immune cells produce a different set of cytokines than younger ones do. For instance, when exposed to antigens, T cells pump out interleukin-2 (IL-2), a cytokine that spurs T cells to divide, thereby activating cell-based immunity. IL-2 signaling decreases with age because naive T cells--which manufacture IL-2--diminish in number, and old memory cells make less IL-2 and its corresponding receptor protein than young memory cells do. Other work suggests that amounts of inflammation-sparking cytokines, in contrast, rise with age, perhaps explaining the prevalence of chronic inflammation in the elderly. Some researchers have surmised that cytokine production shifts from those that stimulate cell-based immunity toward those that spur antibody-based immunity. That pattern isn't clear-cut, however, and conflicting results blur the picture. "When you start an immune response, you get a wide range of cytokines produced, and there's a balance that allows you to have an optimum immune response," says Murasko. "That balance is hard to define."

Scientists have recognized some profound changes in T cells over the human life span, but they are just beginning to understand the mechanisms that underlie these alterations. When antigen docks with a T cell receptor, it tickles signaling mechanisms within the T cell--stimulating enzymes that turn on and off other proteins by tagging them with phosphate groups, increasing calcium concentrations, and spurring production of certain molecules that in turn send messages to other cellular components. These events alter cellular activities, initiating programs that incite the T cell to reproduce and activate its infection-fighting capabilities. According to work by several groups, these signals weaken in old T cells. For instance, upon exposure to an antigen, T cells from aged mice can't crank up the calcium. In addition, the animals stumble at adding phosphate groups to proteins important in relaying the T cell activation signal. One of the first steps in switching on phosphate-adding enzymes is a rearrangement of cytoskeletal proteins after T cell receptors glom onto antigen. And old T cells don't seem to readjust their cytoskeleton when antigens bind, as young T cells do, according to work published in the November 2002 Journal of Immunology (4). Additional studies should further clarify the changes that T cells undergo with age that hinder their protective powers.

Some researchers suggest that old immune cells don't work because they are feeble. Mammalian cells in culture don't divide forever; they eventually grind to a halt, entering a state of senescence in which they neither duplicate nor die (see "More Than a Sum of Our Cells"). Whether the phenomenon is an artifact of culturing or also occurs in animals remains unclear, but Effros suggests that it might come into play in the aging immune system. Like the well-studied connective tissue cells, T cells senesce in culture. Such shut-down cells no longer carry CD28 protein on their surface, and Effros argues that the T cells that lose CD28 in an old animal are likewise senescent. If so, scientists might be able to invigorate the cells by using a trick that revives other types of senescent cells: maintaining chromosome ends. Those ends, called telomeres, protect chromosomes from shriveling; in the absence of telomerase, the enzyme that lengthens telomeres, they shorten with each successive cell division. When they shrink too much, cells senesce. Old T cells without CD28 have shorter telomeres and divide fewer times in culture than do old T cells that retain CD28, according to work by Effros's team. Perhaps keeping telomerase active later in an animal's life would prevent T cell deterioration, Effros suggests. The role of senescence in immune decay isn't locked up, however, and she says that "there are still plenty of nonbelievers."

Antibodies Askew Back to Top

In contrast to T cells, B cells show little change in number with age. In addition, old mice and humans produce approximately the same numbers of antibodies as do their younger counterparts. However, antibodies from the elderly aren't as finely tuned as those produced by younger individuals. They don't bind antigen tightly, and a higher percentage of antibodies grab the body's own molecules instead of the infiltrators'. Thus, older people don't oust pathogens effectively because their antibodies aren't as reliable and because fewer of their antibodies recognize foreign agents. Whether antibodies against the self have a health impact in the elderly is unclear. Such autoantibodies can spur chronic inflammation and tissue damage, which can result in diseases such as type I (juvenile) diabetes, lupus, and rheumatoid arthritis. However, these illnesses arise early in life and aren't considered diseases of aging. Furthermore, the autoantibodies produced by the elderly might be too weak to provoke an immune response. Nevertheless, autoantibodies that accumulate with age might contribute to some diseases of aging, such as atherosclerosis (see "Inflammatory Remarks" below).

Some of the weaknesses in antibodies apparently arise from problems with the cells that train naive B cells to recognize antigens. These so-called follicular dendritic cells reside in regions of lymph nodes known as germinal centers. Some work suggests that this B cell-education system might deteriorate with age. Older mice carry fewer germinal centers in their lymph nodes, for instance. And recent work by immunologist Andras Szakal of Virginia Commonwealth University in Richmond and colleagues suggests that old follicular dendritic cells don't hang on to antigens and B cells as well as young ones do, which could dampen the antibody response (see "Losing Their Grip").

Other B cell assistants also contribute to antibody alterations with aging. Old helper T cells, which join the party in germinal centers, are less proficient than young helper T cells at prodding B cells to make antibody. In particular, CD4+ T cells help spur formation of germinal centers and induce B cells to shuffle their antibody genes, a process that generates new antibody variants to create a tighter fit with antigen. Also, they disseminate fewer B cell-spurring cytokines than do younger T cells. Older mice and humans also accrue clonal expansions of B cells, as they do clonal T cells. In particular, B cells marked by the CD5+ cell surface protein tend to accumulate; CD5+ cells are responsible for producing most autoantibodies. In young animals, CD8+ T cells block these B cells from dividing, but older individuals lose this power.

Innate Immunity Back to Top

Research that probes aging's effect on the innate immune system has lagged behind similar studies of the adaptive immune system. But some results suggest that the adaptive immune system dampens its response, whereas the innate immune system ramps up over time in both animals and people. The elderly carry higher concentrations of several cytokines that prompt inflammation than younger folks do. Why the innate immune system activates isn't clear, but increased exposure to infectious agents or cumulative damage to tissues could spark the change, or a misdirected mechanism to compensate for a quelled adaptive immune response could kick in.

Of the innate immune cells, so-called natural killer (NK) cells are the best studied with respect to aging. NK cells seek out and destroy cells that have been invaded or have turned cancerous, by recognizing a range of chemical changes indicative of the incursion, rather than by recognizing specific antigens as T cells do. NK cells' killing capacity plummets with age, but the number of NK cells increases with age; thus the power of the NK arsenal remains relatively constant as time passes.

The other stars of the innate immune system, macrophages, lose their luster as animals grow old. Although most studies have shown little if any change in macrophages with age, recent work illustrates some defects. Macrophages use surface proteins known as toll-like receptors (TLRs) to recognize foreign bodies. These proteins grasp bits of DNA, membrane, or protein that distinguish friend from foe. When TLRs bind their target, macrophages spew cytokines that summon other immune cells. Macrophages also ingest the prey and chew it into tiny bits; the cells then deliver the bits to B cells and T cells, which initiates an adaptive immune response. Macrophages from old mice carry fewer TLR molecules on their surfaces than do macrophages from young mice, according to work published in the November 2002 Journal of Immunology (5; see "Aging Takes Its Toll"). In addition, old macrophages churned out fewer immune-stimulating cytokines than did young macrophages. The result suggests that some changes in macrophages might cripple the innate immune response in the aged. Because macrophages link the innate immune system to the adaptive immune system, alterations in the cells could have dire consequences for immunity.

Talkin' About an Involution Back to Top

Scientists are also learning more about physiological changes that spur alterations in immune function with age. Perhaps the most profound body change occurs in the thymus, where T cells mature. Precursor stem cells from the bone marrow travel to the thymus and morph into T cells. The mighty thymus also screens and removes T cells that recognize and would attack the host.

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Closing the factory. The thymus from a young mouse (top) carries large numbers of T cell-nurturing thymocytes (dark staining); in old mice (bottom), these cells die and fat takes their place (light staining). [Credit: Dennis Taub/NIH]

Almost immediately after birth, the thymus starts to deteriorate. In a process known as involution, fat cells replace thymus cells and T cell output declines. Researchers formerly thought that the thymus had stopped producing T cells by old age. But several years ago, investigators developed a technique that can detect tiny numbers of new T cells. It traces DNA byproducts--known as TRECs--generated by shuffling of the T cell receptor gene, an event that T cells undergo while maturing in the thymus. Several studies using the technique have demonstrated that the elderly produce new T cells, albeit in smaller quantities than younger individuals do. The old thymus doesn't appear to be proficient enough to bolster the aged immune system, but the new view offers hope that future therapies could rejuvenate the elderly thymus. Growth hormone and insulin-like growth factor-1 seem to stimulate the thymus to produce T cells, says immunologist John Mountz of the University of Alabama, Birmingham. The wisdom of treatment with such hormones remains controversial: The substances are widely touted as antiaging therapy, but laboratory studies largely suggest that the hormones promote, rather than forestall, aging. Whether benefits to the thymus--or any other potential gain--outweigh the detrimental effects of hormone treatment isn't known. Besides, thymic involution is "probably more complex than just hormones," says Mountz. For instance, rodents carrying certain DNA variations that aren't apparently linked to hormone production tend to have thymus glands that deteriorate more rapidly than do those in other animals, Mountz and his colleagues reported last year in Mechanisms of Ageing and Development (6). The researchers hope to track down the identity of the genes involved. Genes that regulate thymus alteration with age could lead researchers to therapies that turn back the thymus's clock and perhaps rejuvenate old T cells' adaptive immune response.

Inflammatory Remarks Back to Top

Paradoxically, the elderly lose adaptive immune function but are often stuck with a low-level innate immune response resulting in chronic inflammation, which can damage tissue. Numerous studies suggest that chronic inflammation promotes aging. For instance, male centenarians more commonly carry two genetic variants that are associated with reduced inflammation than younger men do, according to work published in the April 2003 Journal of Medical Genetics (7). The result suggests that individuals without these gene versions--and who are hence prone to heightened inflammation--tend to die before reaching their 11th decade.

Other work implicates chronic inflammation in specific diseases of aging, particularly Alzheimer's disease (AD) and atherosclerosis. The first hint that inflammation plays a part in AD emerged when researchers noticed that patients with rheumatoid arthritis had an unusually low incidence of the neurodegenerative disease. Further studies suggested that nonsteroidal anti-inflammatory drugs (NSAIDs)--which arthritis patients take to relieve their symptoms--were the key to the protective effect. And studies of tissue from Alzheimer's patients bolster the idea that inflammation contributes to the illness. The plaques that riddle the brains of AD patients contain, in addition to clumps of {beta}-amyloid protein, immune cells called microglia and inflammation-spurring molecules such as cytokines and prostaglandins. Some studies suggest that {beta} amyloid spurs immune cells to spew pro-inflammatory cytokines and that cytokines in turn prod brain cells to make more {beta} amyloid, says pathologist Georg Wick of the Institute for Biomedical Aging Research in Innsbruck, Austria. In such a situation, inflammation can't subside once it starts.

Additional studies have tracked down at least one source of the immune response in AD. Patrick McGeer of the University of British Columbia in Vancouver has found that aggregates of {beta} amyloid activate a collection of proteins known as complement, which picks out and destroys infected cells and triggers inflammation (see McGeer and McGeer Review). These steps are crucial for ridding the body of infection, but in the wrong place, complement might destroy irreplaceable cells. For instance, impaired neurons from people with AD carry a mark of complement's activity: The cells display a group of proteins that the complement pathway inserts into its cellular victims. The protein conglomeration kills cells by blasting through the membrane, causing cellular contents to spill out like guts on a barroom floor. Drugs that specifically target complement might offer better prospects than NSAIDs for combating AD, McGeer proposes.

Complement might not be all bad, however. Blocking one particular complement protein from functioning worsens a mouse version of AD, researchers reported last July, suggesting that complement is protective (see "Taking Complement Well"). McGeer cautions that it's a matter of degree: {beta} amyloid activates human complement much more effectively than it does mouse complement, so the mice probably don't have as severe an inflammatory response as human AD patients do. Thus, inflammation can be protective, but if it gets too severe, it "exacerbates rather than heals the condition," he says.

Wick says that a disease such as AD is "the price we pay" for an active immune system that defends us in youth but harms us later. Other age-related diseases, such as atherosclerosis, might represent a similar tradeoff. Studies over the last 10 years have implied that inflammation contributes to heart disease. Fatty plaques in arteries contain numerous inflammatory cells and molecules. Cholesterol accumulation and injury inflicted by reactive oxygen species (see "The Two Faces of Oxygen") cause blood vessel cells to produce molecules that latch onto immune cells, particularly macrophages, says pathologist Elaine Raines of the University of Washington, Seattle. Those immune cells continually insinuate themselves into the vessel. Eventually the inflammation causes the vessel to weaken and possibly dislodge chunks of tissue that might form heart-stopping clots. Macrophages typically accumulate where vessel breaks later occur, says Raines, and scientists are looking for the molecules produced by macrophages that cause rupturing. The search could reveal potential targets for interventions that soothe inflammation before it turns deadly.

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Stress test. Inflamed heart muscle cells churn out stress proteins (green). Antibodies that latch onto these proteins might further damage the heart. [Credit: Gerald Pfister/Institute for Biomedical Aging Research]

In addition to innate immune components such as macrophages, adaptive immunity also promotes heart disease. People with cardiovascular disease make antibodies that recognize the oxidized lipoproteins that accumulate in atherosclerosis; this observation suggests that those antibodies could spur inflammation that further damages the vessels, setting up a destructive cycle. Wick's team has found that antibodies against the body's stress-response proteins also come into play. Among elderly people, those with severe signs of heart disease carry more antibodies against a stress protein called hsp60. These proteins are quite similar across species, and Wick proposes that antibodies raised against a pathogen's stress protein could cross-react with a person's. When such proteins are produced by cells in the vessel wall--because of high blood pressure, high cholesterol, or chemicals from smoking--the antibodies could attach to the vessel and spark inflammation. Infection might also play an important role, says Raines: Scientists have identified microbial and viral molecules that frequently appear in atherosclerotic plaques, and some studies have linked infection by Chlamydia pneumoniae or cytomegalovirus with the development of atherosclerosis, although their contribution remains unclear.

Tuning Up Immunity Back to Top

Immune changes over time are "not the cause of aging, but they are often the cause of death," says Effros, because an old, faulty immune system promotes illnesses such as heart disease and overlooks scourges such as influenza. And immune health might be a key factor in longevity: In humans, immune function correlates closely with life span, and healthy seniors maintain a more youthful immune system than their ill counterparts do. Furthermore, calorie restriction, which extends the life span of a number of species, also preserves immune spunkiness (see Masoro Review).

To nail down the relation between immune status and aging, scientists must take new tacks. Traditional approaches to studying the aging immune system are complicated by the fact that immune function correlates more strongly with biological age than chronological age. Choosing 30 young and 30 old people doesn't provide a clear picture of how the immune system changes with age, says Grubeck-Loebenstein. Researchers are already planning new studies that compare the healthy elderly to their sickly counterparts, as well as to young people.

Bolstering the immune system might improve health in the elderly, but considerable work remains to be done before scientists gain enough knowledge to design treatments that rejuvenate the elderly immune system. Still, researchers are beginning to set their sights on that goal. Vaccines don't protect old people well; if scientists understood enough, they could presumably tailor these preventives for the elderly population. But "we don't know enough about how vaccines work in the elderly," says Grubeck-Loebenstein. "There aren't enough data." Nevertheless, "companies are putting more and more work into this area." A progressively more sophisticated grasp of the aging immune system will help researchers move toward that goal and design future interventions. One key will be integrating knowledge of how individual elements of the immune system change with age to understand how the pieces interrelate, says Murasko. Further advances might help researchers devise ways to keep the aging immune system as feisty as a trusty watchdog.

June 11, 2003

R. John Davenport is an associate editor of SAGE KE based in Santa Cruz, California. He hopes that getting old won't be an out-of-antibody experience.

Abbreviations: Adaptive immune system. The branch of the immune system in which B cells and T cells produce receptor proteins that recognize specific antigens, molecules characteristic of a pathogen. • Antibodies. Proteins produced by B cells and carried by blood that bind to antigens, thereby marking pathogens for destruction. • Antigens. Substances--usually proteins--recognized by a body as foreign. • Autoantibodies. Antibodies that bind to a body's own molecules. • B cells. Lymphocytes derived from bone marrow stem cells that produce antibodies. • CD4+ T cells. Helper T cells, named for the CD4 protein carried on the cell surface. • CD8+ T cells. Cytotoxic T cells, named for the CD8 protein carried on the cell surface. • Cell-mediated immunity. Immune response driven by T cells rather than by antibodies. It recognizes and destroys infected host cells. • Cytokines. Small proteins that promote or inhibit growth, specialization, or activity of immune cells. • Cytotoxic T cells. T cells that kill other cells after recognizing foreign proteins on the target cell's surface. • Effector cells. Cells that actively carry out an immune function, such as antibody release or cell destruction. • Helper T cells. T cells that promote the activity of other immune cells by releasing activating molecules or by binding to the cells. • Inflammation. Increased blood flow and entry of white blood cells into tissue in response to injury or infection, resulting in swelling, redness, and pain. • Innate immune system. The branch of the immune system that is inherited by an organism and is not altered by exposure to infectious agents. Cells of the innate immune system recognize patterns characteristic of all foreign invaders rather than antigens specific to a particular agent. • Lymphocytes. White blood cells that mature in lymphoid tissue, such as lymph nodes, the spleen, and the thymus. • Lymph nodes. Masses of lymphoid tissue that remove bacteria and other foreign matter from tissue and supply lymphocytes to the blood. • Macrophages. Large cells of the innate immune system that kill host cells infected by foreign invaders. Macrophages also present antigens to B cells and T cells to initiate an adaptive immune response. • Memory cells. B cells and T cells that divide after an initial immune response. These cells retain a memory of the infection and are primed to react to a second exposure. • Naive cells. B cells and T cells that have never bound an antigen. • Natural killer (NK) cells. Cells of the innate immune system that recognize and destroy cancerous or virally infected cells. • Pathogens. Disease-causing agents, usually bacteria, fungi, or viruses. • Senescence. A state attained by old cells in which cell division stops and many genes alter their activities, but the cells do not die. • T cells. Lymphocytes that originate in bone marrow and mature in the thymus. T cells orchestrate cell-mediated immunity. • T cell receptors. TCRs; cell surface proteins produced by T cells that recognize antigens. • Telomeres. Structures made of repetitive bits of DNA sequence and associated proteins that cap the ends of chromosomes. • Thymus. A vertebrate organ in which T cells mature. In mammals, it resides above and in front of the heart.

Suggested ReadingBack to Top

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  • B. Grubeck-Loebenstein and G. Wick, The aging of the immune system. Adv. Immunol. 80, 243-284 (2002). [Abstract]
  • R. J. Hodes, K. S. Hathcock, N. P. Weng, Telomeres in T and B cells. Nat. Rev. Immunol. 2, 699-706 (2002). [Abstract/Full Text]
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Citation: R. J. Davenport, Immunity Challenge. Sci. SAGE KE 2003, oa1 (11 June 2003);2003/23/oa1

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