An induced state in which antigens originally regarded as foreign become regarded as self by the immune system. Tolerance can be induced (tolerization) in all of the cells of the immune system, including T cells (also known as T lymphocytes), the antibody-forming B cells (also known as B lymphocytes), and natural killer cells. Artificially induced immunological tolerance can be helpful in a number of clinical settings.

The special field of medicine that deals with humans in environments encountered beyond the surface of the Earth. Aerospace medicine includes both aviation medicine and space medicine and is concerned with humans, their environment, and the vehicles in which they fly (Fig. 1). Aerospace medicine's objective is to ensure human health, safety, well-being, and effective performance through careful selection and training of flight personnel, protection from the unique physiological and psychological effects of the flight environment, and understanding the flight vehicle and human interaction with the vehicle. See also: Airplane; Astronautics; Aviation; Medicine; Space biology; Space flight

An age-contingent reduction in physiological function and activity, with a concomitant increase in mortality rate and a diminution in reproductive rate. Aging is the process of becoming older, which is influenced by genetic and environmental factors. However, definitions of aging differ between biologists and behavioral scientists. Biologists regard aging as reflecting the sum of multiple and typical biological decrements occurring after sexual maturation; in contrast, behavioral scientists view it as reflecting regular and expected changes occurring in genetically representative organisms advancing through the life cycle under normal environmental conditions. It is difficult to define normal aging because many changes observed in older adults and perceived as concomitants of normal aging are effects of disease in later life. The behavioral science view allows for incremental as well as decremental changes with aging. Senescence is not always equated with aging; it is viewed as the increasing vulnerability or decreasing capacity of an organism to maintain homeostasis as it progresses through its life span, leading to death (Fig. 1). Gerontology refers to the study of aging. Geriatrics refers to the clinical science that is concerned with health and illness in the elderly. See also: Cell (biology); Cell senescence; Death; Genetic influences on aging; Genetics; Human genetics

The repeated and/or excessive use of alcohol (ethanol) that continues despite negative physical, psychiatric, or social consequences. Alcoholism is characterized by consuming alcohol more often, in larger amounts, or over longer periods than intended (Fig. 1); persistent desire or craving of alcohol; and physical consequences of chronic alcohol consumption, especially alcohol tolerance and alcohol withdrawal symptoms during abstinence. Although the initial motivation to consume alcohol results mainly from the expected euphoric effects of alcohol, cue-induced implicit responses, habit, and relief from withdrawal drive continued consumption in the long term. The World Health Organization (WHO) ranks alcohol as one of the primary causes of the global burden of disease in industrialized countries. It is suggested that alcoholism results from an interaction of chronic alcohol exposure, individual genetic makeup, and environmental perturbations over time. This complex gene–environment interaction results in a larger heterogeneity among subjects suffering from alcoholism. See also: Addiction and addictive disorders; Genetics

A class of steroid hormones produced in the testes and adrenal cortex that act to regulate masculine secondary sexual characteristics. The major naturally occurring androgens, such as testosterone, are C-19 steroids (that is, they each contain 19 carbon atoms) with a hydroxyl or ketone group at the C-3 and C-17 positions (see the chemical structure of testosterone in Fig. 1). See also: Adrenal gland; Hormone; Steroid; Testis

A synthetic manufactured drug derived from the male sex hormone testosterone. Androgenic-anabolic steroids, often termed simply as anabolic steroids, are artificially produced testosterone variants. They can provide a number of medical benefits when used properly. However, they have adverse side effects in many instances, and the use of androgenic-anabolic steroids by athletes has been controversial (Fig. 1). See also: Androgen; Hormone; Medicine; Steroid

The condition of exhibiting no immune response to an antigen. Anergy is a self-tolerance mechanism in which the immune system shows unresponsiveness following an encounter with receptor-recognized antigens. Typically, lymphocytes (the B and T cells of the immune system) act to identify and eliminate foreign antigens (for example, bacteria, toxic substances, and cancer cells) that endanger the individual. The recognition of these variable threats relies on the random production and expression of a unique antigen-binding site on almost every lymphocyte. Lymphocytes whose receptors recognize a foreign antigenic substance are subsequently stimulated by that antigen to multiply. These special lymphocytes play a role in the elimination of the antigen or the cells carrying it. Lymphocytes with a surface antigen receptor that specifically recognizes one of an individual's own self-antigens also can be generated, thus creating the potential for autoimmunity (reaction against one's own cells). Nevertheless, the clinical appearance of autoimmune disease is relatively rare because most individuals possess effective self-tolerance mechanisms to control such autoreactive cells. One major mechanism is clonal deletion: lymphocytes are killed if they recognize a self-antigen during their maturation in the thymus gland (for T cells) or bone marrow (for B cells). However, not all human self-antigens are expressed in these central lymphoid organs while the lymphocytes are developing. Thus, tolerance to an individual's own antigens must also depend on other means, including the self-tolerance mechanism of clonal anergy. Theoretically, autoreactive lymphocytes lose their capacity to multiply following their recognition of a self-antigen in the peripheral immune system. See also: Acquired immunological tolerance; Antigen; Autoimmunity; Cellular immunology; Immunology; Immunosuppression

The use of live nonhuman animals for scientific research and experimentation. Animal testing has been a cornerstone of biomedical research, having contributed greatly to the understanding of human biology, to the unraveling of the complex underlying causes and effects of disease, and to the development and testing of effective and safe means of diagnosis and treatment. However, the use of sentient beings as disease models and test subjects (Fig. 1) raises a significant ethical dilemma between animal harm and human benefits. Faced with this dilemma, the mainstream ethical, social, and political stance has been to deem it acceptable only when no alternatives are available, if aimed at answering meaningful scientific or medical questions, and provided animal harm is minimized. Some individuals, however, advocate that no animal use in science is morally justified, regardless of any potential benefits. Further fueling the discussion, the medical value of animal experiments has been increasingly challenged. Scientists, companies, regulators, and funders are responding by improving transparency regarding why and how animals are used in science, while working continuously to raise standards and make animal experiments more reliable, humane, and relevant. With this as a background, the 3Rs principle for replacement, reduction, and refinement offers a meaningful and ever-improving approach to ease the pressing ethical and scientific challenges at hand. See also: Bioethics; Biology; Biotechnology; Experiment; Medicine; Pharmaceuticals testing; Scientific methods

Any substance that causes the immune system to produce specific antibodies or T cells against it. An antigen may be a foreign substance from the environment (such as chemicals, bacterial or viral proteins, or pollen; Fig. 1) or formed within the host's own body. Reactions of antigens with antibodies or T cells (thymic lymphocytes, a type of white blood cells), which are capable of activating or suppressing immune reactions as well as attacking other cells] serve as a defense against microorganisms and other foreign bodies, but can be detrimental if the immune response is mounted against the "self," as in autoimmune disorders. Antigen-antibody complexes are used in laboratory tests for detecting the presence of either antigen or antibody to determine a subject's previous exposure to pathogens. See also: Antibody; Antigen-antibody reaction; Autoimmunity; Immunologic cytotoxicity; Immunology; Immunopathology; Pathogen

Any treatment or procedure that includes the in-vitro handling of oocytes (immature ova or egg cells) and sperm or embryos for the purpose of establishing a pregnancy. Assisted reproductive technology (ART) is undertaken as a treatment of infertility, with a goal of achieving human reproduction. ART procedures include (but are not limited to) in-vitro fertilization (IVF) and embryo transfer (ET) [Fig. 1], gamete intrafallopian transfer, gamete and embryo cryopreservation (freezing, or vitrification, and storage of cells or tissues), oocyte and embryo donation, and surrogacy. Note that intracervical or intrauterine insemination with either partner or donor spermatozoa is not included under the umbrella of ART. See also: Animal reproduction; Biotechnology; Fertilization (animal); Infertility; Ovum; Pregnancy; Sperm cell