Immune Response to Infection

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Immune Response to Infection

Introduction

Scientific Foundations

Impacts and Issues

Primary Source Connection

BIBLIOGRAPHY

Introduction

The immune system is a series of cells, tissues, organs, and processes in the body that differentiates the self from foreign bodies, fights infections, and develops immunity against future attack. The function of the immune system is to identify pathogens (disease-causing organisms) of all types and to destroy them through immune processes. Bacteria, viruses, fungi, parasites, cancerous cells, and single-celled organisms such as amoebas can all attack the body and cause disease. The immune system must recognize and act on these pathogens without attacking its own healthy tissues, thereby causing illness. The immune system also works to keep dangerous pathogens out of the body. This is an important function of the skin and mucous membranes, which have high concentrations of immune system cells: resisting, trapping, and killing microorganisms, preventing them from causing disease.

Scientific Foundations

One of the most important jobs of the immune system is to differentiate the self from the non-self. Almost all the cells of the body have specific proteins on their surfaces that identify them as “self.” This is referred to at the major histocompatibility complex (MHC) protein. Foreign bodies, like bacteria, viruses, or cells belonging to another organism lack the appropriate MHC protein and are thus identified as “non-self.” The healthy immune system reacts to things identified as non-self and not to things identified as self.

Many organs in the body are regarded as part of the immune system because they produce, transport, coordinate, or help mature immune cells. The bone marrow is often considered first because it is the source of all blood and immune cells. The thymus is the developing ground for T-cells (a lymphocyte, or white blood cell that fights pathogens), where large numbers of unsuitable cells undergo apoptosis (programmed cell death) for each mature T-cell that is produced. One of the functions of the spleen is to store and release generalized immune cells to respond to infection. Other lymphoid organs, such as the tonsils, adenoids, and appendix, are placed strategically in the respiratory and digestive tracts to intercept infectious agents before they enter further into the body.

The lymphatic system is a complex network of vessels and nodes that transport lymph, a fluid very similar to blood plasma. The lymph system connects the organs of the immune system with one another and with the rest of the body, carrying immune cells to their necessary locations. Lymph nodes are small compartments that provide space for immune cells to interact with antigens and begin their response. They also allow transfer of immune cells between the lymph system and the circulatory system. Unlike the blood, which is pumped around the body at high pressure by the heart, the lymph fluid is slow-moving and at low pressure, lacking a central pump. The lymph fluid is extracted from the body's tissues by osmosis, and then is transported around the body by the movement of muscles. Because of its slow-moving nature, lymph fluid can sometimes build up in the limbs, causing swelling and the possibility of infection. This is called lymphedema.

Anything that the immune system responds to, whether it is a microbe, protein, virus, or fragment of a pathogen, is called an antigen. The presence of antigens activates specific immune cells to destroy the pathogen and teach the immune system to recognize it in the future. There are two major kinds of immune cells: those that react generally to all pathogens and those that are keyed to a specific disease-causing agent. Generalized immune cells include neutrophils, which consume pathogens and kill them with powerful chemical granules, and then send signals to other cells. Macrophages then arrive to consume the foreign bodies. Natural killer cells also use toxic granules to kill disease agents, responding to cells lacking the correct MHC proteins.

Lymphocytes, also known as white blood cells, are produced in the bone marrow and are present in the blood. From the bone marrow, certain lymphocytes known as T-cells travel to an organ known as the thymus to mature. Lymphocytes are also carried around the body by the lymphatic system. Two major types of lymphocytes react to specific pathogens. B-cells create anti-bodies, while T-cells destroy invaders and coordinate the overall immune response. Antibodies are special markers that lock onto antigens and alert the T-cells to destroy them. Cells use proteins called cytokines to communicate that they are injured and to organize immune cells.

After a pathogen has been detected and destroyed, a small number of antibodies and specialized T-cells remain to guard against future attack. When that same pathogen is encountered again, the number of specialized cells multiplies to mount an immune response.

Impacts and Issues

The generalized immune system cells provide innate immunity, the ability to identify a foreign body and destroy it without having been exposed to it previously. Once the immune system has encountered a pathogen, activated its immune cells, and developed antibodies, the body is said to have developed acquired (or adaptive) immunity. Vaccines provide resistance from diseases that the body has not encountered by causing the production of antibodies. Thus, vaccines induce a kind of acquired immunity. Nursing infants also obtain antibodies and immune system proteins from their mothers when they breast-feed. This is widely recognized as one of the benefits of nursing, since the immune system of infants is immature at birth.

One of the first bodily responses to infection or injury is inflammation, the familiar redness, swelling, heat, and pain associated with trauma. Inflammation is initiated locally by the blood vessels in the infected area. The activated vessels release fluids, which cause the swelling, as well as cytokines, which send signals to the immune system. This causes white blood cells of all types to rush to the area. The white blood cells begin acting on pathogens in their customary ways, identifying and consuming pathogens and creating antibodies. The cytotoxic (toxic to cells) chemicals present in neutrophils and other granulocytes are also responsible for reinforcing the inflammatory response. Inflammation can become harmful when it moves from a localized response to a systemic condition. Some heart problems, asthma, blood vessel disease, colitis (bowel disease), arthritis, fibromyalgia, and nephritis (kidney disease) are all associated with excessive or inappropriate inflammation.

WORDS TO KNOW

ACQUIRED (ADAPTIVE) IMMUNITY: Immunity is the ability to resist infection and is sub-divided into innate immunity, which an individual is born with, and acquired, or adaptive, immunity, which develops according to circumstances and is targeted to a specific pathogen. There are two types of acquired immunity, known as active and passive. Active immunity is either humoral, involving production of antibody molecules against a bacterium or virus, or cell-mediated, where T-cells are mobilized against infected cells. Infection and immunization can both induce acquired immunity. Passive immunity is induced by injection of the serum of a person who is already immune to a particular infection.

ANTIBODY: Antibodies, or Y-shaped immunoglobulins, are proteins found in the blood that help to fight against foreign substances called antigens. Antigens, which are usually proteins or polysaccharides, stimulate the immune system to produce antibodies. The antibodies inactivate the antigen and help to remove it from the body. While antigens can be the source of infections from pathogenic bacteria and viruses, organic molecules detrimental to the body from internal or environmental sources also act as antigens. Genetic engineering and the use of various mutational mechanisms allow the construction of a vast array of antibodies (each with a unique genetic sequence).

ANTIGEN: Antigens, which are usually proteins or polysaccharides, stimulate the immune system to produce antibodies. The antibodies inactivate the antigen and help to remove it from the body. While antigens can be the source of infections from pathogenic bacteria and viruses, organic molecules detrimental to the body from internal or environmental sources also act as antigens. Genetic engineering and the use of various mutational mechanisms allow the construction of a vast array of antibodies (each with a unique genetic sequence).

CYTOKINE: Cytokines are a family of small proteins that mediate an organism's response to injury or infection. Cytokines operate by transmitting signals between cells in an organism. Minute quantities of cytokines are secreted, each by a single cell type, and regulate functions in other cells by binding with specific receptors. Their interactions with the receptors produce secondary signals that inhibit or enhance the action of certain genes within the cell. Unlike endocrine hormones, which can act throughout the body, most cytokines act locally near the cells that produced them.

INNATE IMMUNITY: Innate immunity is the resistance against disease that an individual is born with, as distinct from acquired immunity that develops with exposure to infectious agents.

LYMPHOCYTE: A type of white blood cell; includes B and T lymphocytes. A type of white blood cell that functions as part of the lymphatic and immune systems by stimulating antibody formation to attack specific invading substances.

MAJOR HISTOCOMPATIBILITY COMPLEX (MHC): The proteins that protrude from the surface of a cell that identify the cell as “self.” In humans, the proteins coded by the genes of the major histocompatibility complex (MHC) include human leukocyte antigens (HLA), as well as other proteins. HLA proteins are present on the surface of most of the body's cells and are important in helping the immune system distinguish “self” from “non-self” molecules, cells, and other objects.

NEUTROPHIL: An immune cell that releases a bacteria-killing chemical; neutrophils are prominent in the inflammatory response. A type of white blood cell that phagocytizes foreign microorganisms; also releases lysozyme.

PATHOGEN: A disease causing agent, such as a bacteria, virus, fungus, etc.

Disorders of the immune system can cause serious disease. HIV is a well-known virus that attacks the helper T-cells, which activate and manage immune response. Once levels of helper T-cells fall to sufficiently low levels, the normal immune response breaks down and the victim becomes more susceptible to opportunistic infections. Many types of autoimmune diseases are the result of the immune system attacking the body. Crohn's disease, type I diabetes, rheumatoid arthritis, multiple sclerosis, myasthenia gravis, celiac disease, and Addison's disease are among the serious conditions associated with misdirected immune response. It should be noted that some developmental processes and the destruction of cancer require the immune system to act upon the self, and so not all autoimmune responses are harmful.

All organisms require defense from invasive pathogens. In humans and other vertebrates, the intricate and multi-layered protection provided by the organs, cells, proteins, and chemicals of the immune systems provides resistance to many kinds of attack. Even single-celled organisms use chemical substances to defend themselves. The proper function of the immune system is necessary for the health of the organism, avoiding both infection and autoimmune disease. Without the immune system, the body would be susceptible to endless attack, shortening lifespan or even making life impossible.

Primary Source Connection

Why an unequal society is an unhealthy society: poor relationships and low status don't just make people envious. They also interfere with the immune system and damage health.

Among those who see the mind as the work of natural selection, there is a sense that the time has come: we are beginning to understand what we really are.

From the construction boom in Darwinian theory, two major propositions have emerged, sustained by confidence that supporting data will increasingly be delivered in hard genetic currency. One is that human nature is evolved and universal; the other is that variations in personality and mental capabilities are substantially inherited. The first speaks of the species and the second about individuals. That leaves society—and here a third big idea is taking shape. In two words, inequality kills.

The phrase (which is that of Richard Wilkinson, one of the leading researchers in the field) sticks out from the current consensus like a sore thumb. For the most part, the major biological ideas concerning human nature and mental capabilities tend to confirm the way the world has turned out.

But what might be the biggest biological idea of all, in terms of its implications for human health and happiness, shows the world in a very different light. It finds that society has a profound influence over the length and quality of individuals’ lives. The bodies of data are legion and the message from them is clear: unequal societies are unhealthy societies. They are unhealthy not just in the strict sense, but also in the wider one, that they are hostile, suspicious, antagonistic societies.

The most celebrated studies in this school of thought are those conducted among Whitehall civil servants by Michael Marmot, who presents his ideas in popular form in his recent book Status Syndrome. He and his colleagues found a steady gradient in rates of death between the lowest and the highest ranks of the civil service hierarchy. Top civil servants were less likely to die of heart disease than their immediate subordinates, and so on down the ladder; at the bottom, the lowest grades were four times more likely to die than the uppermost.

The main features of these findings were that the gradient was continuous, and that only about a third of the effect vanished when account was taken of the usual lifestyle suspects such as smoking and fatty food. This influence upon life and death affected everybody in the hierarchy, according to their position in it. Differences in wealth were an implausible cause in themselves, for most of the civil servants were comfortably off and even the lowest-paid were not poor. The fatal differences were those of status.

What goes for Whitehall seems to go for the world. In rich countries, death rates appear to be related to the differences between incomes, rather than to absolute income levels. The more unequally wealth is distributed, the higher homicide rates are likely to be. Although the findings about income inequality are controversial, the broad picture is consistent; and remains so when softer criteria than death are measured—for instance, trust or social cohesion. Inequality promotes hostility, frustrates trust and damages health.

It is hard to make sense of these findings outside a framework based on the idea of an evolved psychology. However, understanding humans as evolved social beings, made what we are by the selective pressures of life in groups of intelligent beings, it is easy to see that our minds and bodies depend upon our relations with our kind. These relations assume central importance for our health once economic development has minimised the dangers of infectious disease and relegated starvation to history.

Studies of baboons, social primates obliged by their nature to form hierarchies, tell the same story. A state of subordination is stressful; such stress may put the body into a mode that is vital in emergencies but corrosive as a permanent condition, interfering with the immune system and increasing the risk of heart disease. Conversely, human relationships formed on a broadly equal basis may support the immune system and promote health.

An American researcher, Sheldon Cohen, demonstrated this by dripping cold viruses into volunteers’ noses, and then asking them about the range and frequency of their social relationships. The more connections they had— with acquaintances, colleagues, neighbours and fellow club members as well as with nearest and dearest—the less likely they were to develop colds.

The relationship between the length of life and its everyday quality is the relationship between its biological and social dimensions, which demands an evolutionary explanation; and the findings seem to demand egalitarian measures. Such Darwinian readings of the data on health and equality do not confound claims that humans are innately unequal. They do, however, lead to different views of how to make the best of people.

So do the prior ethical commitments that evolutionary thinkers bring to their projects. In his book The Blank Slate, having stated that all human characteristics are substantially impervious to parental influence, the psychologist Steven Pinker denounces the past century's art and related theories of art. Folk wisdom and popular taste are right, he affirms; “elite art” is perverse and wrong. The argument, built upon the idea that we all share an evolved human nature, is a standard-issue right-leaning castigation of the liberal elite.

Pinker takes his moral bearings from literary reference points, such as Nineteen Eighty-Four, that affirm the individual and condemn attempts to impose equality upon humankind's natural inequality. Modern Darwinism of this kind holds that evolutionary processes act on individual organisms rather than upon groups of organisms.

It makes no particularly strong predictions about variations among individual minds. That part of the picture comes from the behaviour geneticists, who compare identical twins with fraternal twins (or study their prize specimens, identical twins who have been reared apart) and conclude that a large proportion of the variation between individuals’ personality traits, temperaments and intelligence is due to inherited differences.

Such findings readily lend themselves to a view of the world which attaches great importance to allowing individuals to fulfil their potential, while regarding social programmes to reduce inequalities as vain at best. Equality of opportunity is a fundamental principle; equality of outcome is a pernicious fantasy.

The result is an upbeat fatalism: upbeat about the prospects for scientific understanding of human psychology, fatalistic about the prospects that society might be improved by such understanding, and upbeat, also, in the confidence that society needs no radical alteration. Many of those who dislike such visions collude in them by acquiescing in the assumption that the effects of environments can be altered, but those of genes cannot.

The big idea that provides much of the driving force for evolutionary psychology, the project to describe a universal human nature, is that the sexes have different reproductive interests. The sex which invests the most in reproduction will be the one which takes more care in choosing its mates. Among humans, this implies that women will tend to be more discriminating than males in their choice of partners. It also implies that men and women will have different emotional propensities—as Stephen Jay Gould put it, conceding the central principle of evolutionary psychology in the very act of deploring the neoDarwinian school. It does not imply that every woman will be more circumspectin choice of partners than every man, or that every man will be readier to take risks than every woman, any more than the tendency for men to be taller than women means that all men are taller than all women. Through the widespread failure to recognise that evolved behaviours and ways of thinking are tendencies, evolutionary psychology has determinism thrust upon it.

In the application of evolutionary perspectives to health and equality, however, the prospect of a better society— or at least of better communities or workplaces—is unmistakable. This way of understanding human nature has the qualities that have marked great Darwinian ideas since The Origin of Species: it is profound in its implications, potentially transformative, and it challenges existing wisdom. On the one hand, it calls into question the idea that equality of opportunity should be pursued without regard for equality of outcome. On the other, it goes beyond the assumption that the task of “progressive” politics is to ensure that the least well-off have enough, and instead emphasises that how much is enough depends on how much others have.

The application of natural selection to social justice replaces vestigial sentiments about the abstract virtue of co-ops and community spirit with hard data about life and death, implying that we would all (or almost all) be healthier and happier if we were prepared to share more of what we have. Above all, it speaks to the world we live in, where want is marginal but trust is precarious. In Richard Wilkinson's words, it is “the science of social justice.”

Like other big evolutionary ideas, however, it may be honoured more by denial than by engagement.

Marek Kohn

KOHN, MAREK. “WHY AN UNEQUAL SOCIETY IS AN UNHEALTHY SOCIETY: POOR RELATIONSHIPS AND LOW STATUS DON'T JUST MAKE PEOPLE ENVIOUS. THEY ALSO INTERFERE WITH THE IMMUNE SYSTEM AND DAMAGE HEALTH.” NEW STATESMAN (1996) 133.4698 (JULY 26, 2004): P30(2).

See AlsoBacterial Disease; HIV; Vaccines and Vaccine Development; Viral Disease; Water-borne Disease.

BIBLIOGRAPHY

Web Sites

Bugl, Paul. “Immune System.” University of Hartford. <http://uhaweb.hartford.edu/BUGL/immune.htm> (accessed June 13, 2007).

Carter, J. Stein. “Immune System.” University of Cincinnati. <http://biology.clc.uc.edu/Courses/bio105/immune.htm> (accessed June 13, 2007).

National Center for Biotechnology Information. “Diseases of the Immune System.” <http://www.ncbi.nlm.nih.gov/disease/Immune.html> (accessed June 13, 2007).

National Institute of Allergy and Infectious Disease. “Understanding the Immune System.” <http://health.nih.gov/viewPublication.asp?disease_id=63&publication_id=2841pdf=yes> (accessed June 13, 2007).

Kenneth T. LaPensee