Anergy
Encyclopedia
Anergy is a term in immunobiology that describes a lack of reaction by the body's defense mechanisms to foreign substances, and consists of a direct induction of peripheral lymphocyte
tolerance
. An individual in a state of anergy often indicates that the immune system
is unable to mount a normal immune response against a specific antigen
, usually a self-antigen. Lymphocytes are said to be anergic when they fail to respond to their specific antigen. Anergy is one of three processes that induce tolerance induction, modifying the immune system to prevent self-destruction (the others being clonal deletion
and immunoregulation).
and termed "Clonal Anergy." The clones of B lymphocytes in this case can still be found alive in the circulation, but are very ineffective at mounting immune responses. Later Ronald Schwartz and Marc Jenkins described a similar process operating in the T lymphocyte. Many viruses (HIV
being the most extreme example) seem to exploit the immune system's use of tolerance induction to evade the immune system, though the suppression of specific antigens is done by fewer pathogens (notably Mycobacterium leprae
).
At the cellular level, the term "anergy" defines the inability of an immune cell to mount a complete response against its target. In the immune system, circulating cells called lymphocytes form a primary army that defends the body against pathogenic virus
es, bacteria
and parasites. There are two major kinds of lymphocytes - the T lymphocyte and the B lymphocyte. Among the millions of lymphocytes in the human body, only a few actually are specific for any particular infectious agent. At the time of infection, these few cells must be recruited and allowed to multiply rapidly. This process - called "clonal expansion" - allows the body to quickly mobilise an army of clones, as and when required. This clonal army then combats the pathogen
until the body is free of the infection. Following clearance of the infection, the clones that are no longer needed die away naturally.
However, a small number of the body's army of lymphocytes are able to react with proteins that are normally present in a healthy body. The clonal expansion of those cells can lead to autoimmune diseases, wherein the body attacks itself. In order to prevent this process, lymphocytes possess an intrinsic quality-control mechanism. This machinery shuts down the lymphocytes' ability to expand, if the trigger for the expansion turns out to be the body's own protein. T-cell anergy can arise when the T-cell does not receive appropriate co-stimulation in the presence of specific antigen recognition. B-cell anergy can be induced by exposure to soluble circulating antigen, and is often marked by a downregulation of surface IgM
expression and partial blockade of intracellular
signaling pathways.
, multiple sclerosis
and rheumatoid arthritis
. Likewise, preventing anergy in response to a tumoral growth may help in anti-tumor responses.
) is used with seven antigens of bacterial or fungal origin (tetanus toxoid, tuberculin
, diphtheria
, streptococcus
, candida
, trichophyton
, and proteus
). In this test reactions are categorized according to the number of antigens provoking a response and the summed extent of the skin response to all seven antigens. Here anergy is defined as a region of skin reactivity of 0-1 mm, hypoergy as a reaction of 2–9 mm in response to fewer than three antigens, normoergy as a reaction of 10–39 mm or to three or more antigens, and hyperergy for a reaction of 40 mm or more.
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
tolerance
Immune tolerance
Immune tolerance or immunological tolerance is the process by which the immune system does not attack an antigen. It can be either 'natural' or 'self tolerance', in which the body does not mount an immune response to self antigens, or 'induced tolerance', in which tolerance to external antigens can...
. An individual in a state of anergy often indicates that the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
is unable to mount a normal immune response against a specific antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
, usually a self-antigen. Lymphocytes are said to be anergic when they fail to respond to their specific antigen. Anergy is one of three processes that induce tolerance induction, modifying the immune system to prevent self-destruction (the others being clonal deletion
Clonal deletion
Clonal deletion is a process by which B cells and T cells are deactivated after they have expressed receptors for self-antigens and before they develop into fully immunocompetent lymphocytes.It is one method of immune tolerance....
and immunoregulation).
Mechanism
This phenomenon was first described in B lymphocytes by Gustav NossalGustav Nossal
Sir Gustav Victor Joseph Nossal, AC, CBE, FRS, FAA is an Australian research biologist.-Life and career:Gustav Nossal's family was from Vienna, Austria. He was born four weeks prematurely in Bad Ischl while his mother was on holiday...
and termed "Clonal Anergy." The clones of B lymphocytes in this case can still be found alive in the circulation, but are very ineffective at mounting immune responses. Later Ronald Schwartz and Marc Jenkins described a similar process operating in the T lymphocyte. Many viruses (HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
being the most extreme example) seem to exploit the immune system's use of tolerance induction to evade the immune system, though the suppression of specific antigens is done by fewer pathogens (notably Mycobacterium leprae
Mycobacterium leprae
Mycobacterium leprae, also known as Hansen’s coccus spirilly, mostly found in warm tropical countries, is a bacterium that causes leprosy . It is an intracellular, pleomorphic, acid-fast bacterium. M. leprae is an aerobic bacillus surrounded by the characteristic waxy coating unique to mycobacteria...
).
At the cellular level, the term "anergy" defines the inability of an immune cell to mount a complete response against its target. In the immune system, circulating cells called lymphocytes form a primary army that defends the body against pathogenic virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es, bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
and parasites. There are two major kinds of lymphocytes - the T lymphocyte and the B lymphocyte. Among the millions of lymphocytes in the human body, only a few actually are specific for any particular infectious agent. At the time of infection, these few cells must be recruited and allowed to multiply rapidly. This process - called "clonal expansion" - allows the body to quickly mobilise an army of clones, as and when required. This clonal army then combats the pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
until the body is free of the infection. Following clearance of the infection, the clones that are no longer needed die away naturally.
However, a small number of the body's army of lymphocytes are able to react with proteins that are normally present in a healthy body. The clonal expansion of those cells can lead to autoimmune diseases, wherein the body attacks itself. In order to prevent this process, lymphocytes possess an intrinsic quality-control mechanism. This machinery shuts down the lymphocytes' ability to expand, if the trigger for the expansion turns out to be the body's own protein. T-cell anergy can arise when the T-cell does not receive appropriate co-stimulation in the presence of specific antigen recognition. B-cell anergy can be induced by exposure to soluble circulating antigen, and is often marked by a downregulation of surface IgM
IGM
IGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...
expression and partial blockade of intracellular
Intracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
signaling pathways.
Clinical significance
Anergy may be taken advantage of for therapeutic uses. The immune response to grafting of transplanted organs and tissues could be minimized without weakening the entire immune system— a side effect of immunosuppressive drugs like cyclosporine. Anergy may also be used to induce activated lymphocytes to become unresponsive with autoimmune diseases like diabetes mellitusDiabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
, multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
and rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
. Likewise, preventing anergy in response to a tumoral growth may help in anti-tumor responses.
Testing
The "Multitest Mérieux" or "CMI Multitest" system (Multitest IMC, Istituto Merieux Italia, Rome, Italy) has been used as a general test of the level of cellular immunity. It is an intradermal test of skin reactivity (similar to tuberculin tests) in which a control (glycerolGlycerol
Glycerol is a simple polyol compound. It is a colorless, odorless, viscous liquid that is widely used in pharmaceutical formulations. Glycerol has three hydroxyl groups that are responsible for its solubility in water and its hygroscopic nature. The glycerol backbone is central to all lipids...
) is used with seven antigens of bacterial or fungal origin (tetanus toxoid, tuberculin
Tuberculin
Tuberculin is the name given to extracts of Mycobacterium tuberculosis, M. bovis, or M. avium that is used in skin testing in animals and humans to identify a tuberculosis infection. Several types of tuberculin have been used for this, of which purified protein derivative is the most important....
, diphtheria
Diphtheria
Diphtheria is an upper respiratory tract illness caused by Corynebacterium diphtheriae, a facultative anaerobic, Gram-positive bacterium. It is characterized by sore throat, low fever, and an adherent membrane on the tonsils, pharynx, and/or nasal cavity...
, streptococcus
Streptococcus
Streptococcus is a genus of spherical Gram-positive bacteria belonging to the phylum Firmicutes and the lactic acid bacteria group. Cellular division occurs along a single axis in these bacteria, and thus they grow in chains or pairs, hence the name — from Greek στρεπτος streptos, meaning...
, candida
Candida (genus)
Candida is a genus of yeasts. Many species are harmless commensals or endosymbionts of animal hosts including humans, but other species, or harmless species in the wrong location, can cause disease. Candida albicans can cause infections in humans and other animals, especially in immunocompromised...
, trichophyton
Trichophyton
The fungus genus Trichophyton is characterized by the development of both smooth-walled macro- and microconidia. Macroconidia are mostly borne laterally directly on the hyphae or on short pedicels, and are thin- or thick-walled, clavate to fusiform, and range from 4 to 8 by 8 to 50 um in size....
, and proteus
Proteus
In Greek mythology, Proteus is an early sea-god, one of several deities whom Homer calls the "Old Man of the Sea", whose name suggests the "first" , as protogonos is the "primordial" or the "firstborn". He became the son of Poseidon in the Olympian theogony In Greek mythology, Proteus (Πρωτεύς)...
). In this test reactions are categorized according to the number of antigens provoking a response and the summed extent of the skin response to all seven antigens. Here anergy is defined as a region of skin reactivity of 0-1 mm, hypoergy as a reaction of 2–9 mm in response to fewer than three antigens, normoergy as a reaction of 10–39 mm or to three or more antigens, and hyperergy for a reaction of 40 mm or more.