Misplaced Pages

#75924

117-427: The immune system has innate and adaptive components. Innate immunity is present in all metazoans , immune responses: inflammatory responses and phagocytosis . The adaptive component, on the other hand, involves more advanced lymphatic cells that can distinguish between specific "non-self" substances in the presence of "self". The reaction to foreign substances is etymologically described as inflammation while

234-564: A lysosome to form a phagolysosome . The pathogen is killed by the activity of digestive enzymes or following a respiratory burst that releases free radicals into the phagolysosome. Phagocytosis evolved as a means of acquiring nutrients , but this role was extended in phagocytes to include engulfment of pathogens as a defense mechanism. Phagocytosis probably represents the oldest form of host defense, as phagocytes have been identified in both vertebrate and invertebrate animals. Neutrophils and macrophages are phagocytes that travel throughout

351-465: A "self" receptor called a major histocompatibility complex (MHC) molecule. There are two major subtypes of T cells: the killer T cell and the helper T cell . In addition there are regulatory T cells which have a role in modulating immune response. Killer T cells are a sub-group of T cells that kill cells that are infected with viruses (and other pathogens), or are otherwise damaged or dysfunctional. As with B cells, each type of T cell recognizes

468-423: A chemical barrier following menarche , when they become slightly acidic , while semen contains defensins and zinc to kill pathogens. In the stomach , gastric acid serves as a chemical defense against ingested pathogens. Within the genitourinary and gastrointestinal tracts, commensal flora serve as biological barriers by competing with pathogenic bacteria for food and space and, in some cases, changing

585-422: A condition known as "missing self". This term describes cells with low levels of a cell-surface marker called MHC I ( major histocompatibility complex )—a situation that can arise in viral infections of host cells. Normal body cells are not recognized and attacked by NK cells because they express intact self MHC antigens. Those MHC antigens are recognized by killer cell immunoglobulin receptors, which essentially put

702-584: A different antigen. Killer T cells are activated when their T-cell receptor binds to this specific antigen in a complex with the MHC Class I receptor of another cell. Recognition of this MHC:antigen complex is aided by a co-receptor on the T cell, called CD8 . The T cell then travels throughout the body in search of cells where the MHC I receptors bear this antigen. When an activated T cell contacts such cells, it releases cytotoxins , such as perforin , which form pores in

819-533: A diminished effect and may result in lower antibody production, and a lower immune response, than would be noted in a well-rested individual. Additionally, proteins such as NFIL3 , which have been shown to be closely intertwined with both T-cell differentiation and circadian rhythms , can be affected through the disturbance of natural light and dark cycles through instances of sleep deprivation. These disruptions can lead to an increase in chronic conditions such as heart disease, chronic pain, and asthma. In addition to

936-503: A full theory of immunity was Ilya Mechnikov who revealed phagocytosis in 1882. With Louis Pasteur 's germ theory of disease , the fledgling science of immunology began to explain how bacteria caused disease, and how, following infection, the human body gained the ability to resist further infections. In 1888 Emile Roux and Alexandre Yersin isolated diphtheria toxin , and following the 1890 discovery by Behring and Kitasato of antitoxin based immunity to diphtheria and tetanus ,

1053-442: A large dose of mithridate as a precaution against the plague and found it cured his acne . The term mithridate has come to refer to any generally all-purpose antidote. Mithridates' father was assassinated by poisoning, according to some at his mother's orders. After this, Mithridates's mother held regency over Pontus until a male heir was of age. Mithridates was in competition with another brother, whom his mother favored, for

1170-399: A link between the bodily tissues and the innate and adaptive immune systems, as they present antigens to T cells , one of the key cell types of the adaptive immune system. Granulocytes are leukocytes that have granules in their cytoplasm. In this category are neutrophils, mast cells, basophils, and eosinophils. Mast cells reside in connective tissues and mucous membranes and regulate

1287-413: A pathogen, memory B-cells and T- cells develop, and the primary immune response results. Throughout the lifetime of an animal, these memory cells will "remember" each specific pathogen encountered, and can mount a strong secondary response if the pathogen is detected again. The primary and secondary responses were first described in 1921 by English immunologist Alexander Glenny although the mechanism involved

SECTION 10

#1732856035076

1404-434: A primary immune response , this leads to immunological memory. Many disorders of immune system function can affect the formation of active immunity, such as immunodeficiency (both acquired and congenital forms) and immunosuppression . Artificially acquired active immunity can be induced by a vaccine , a substance that contains antigen. A vaccine stimulates a primary response against the antigen without causing symptoms of

1521-460: A pro-inflammatory state through the production of the pro-inflammatory cytokines interleukin-1, interleukin-12 , TNF-alpha and IFN-gamma . These cytokines then stimulate immune functions such as immune cell activation, proliferation, and differentiation . During this time of a slowly evolving adaptive immune response, there is a peak in undifferentiated or less differentiated cells, like naïve and central memory T cells. In addition to these effects,

1638-491: A reduced ability to destroy pathogens, is an example of an inherited, or congenital, immunodeficiency . AIDS and some types of cancer cause acquired immunodeficiency. Overactive immune responses form the other end of immune dysfunction, particularly the autoimmune diseases . Here, the immune system fails to properly distinguish between self and non-self, and attacks part of the body. Under normal circumstances, many T cells and antibodies react with "self" peptides. One of

1755-416: A rudimentary immune system in the form of enzymes that protect against viral infections. Other basic immune mechanisms evolved in ancient plants and animals and remain in their modern descendants. These mechanisms include phagocytosis , antimicrobial peptides called defensins , and the complement system . Jawed vertebrates , including humans, have even more sophisticated defense mechanisms, including

1872-471: A single MHC:antigen molecule. Helper T cell activation also requires longer duration of engagement with an antigen-presenting cell. The activation of a resting helper T cell causes it to release cytokines that influence the activity of many cell types. Cytokine signals produced by helper T cells enhance the microbicidal function of macrophages and the activity of killer T cells. In addition, helper T cell activation causes an upregulation of molecules expressed on

1989-460: A specific foreign antigen. This antigen/antibody complex is taken up by the B cell and processed by proteolysis into peptides . The B cell then displays these antigenic peptides on its surface MHC class II molecules. This combination of MHC and antigen attracts a matching helper T cell, which releases lymphokines and activates the B cell. As the activated B cell then begins to divide , its offspring ( plasma cells ) secrete millions of copies of

2106-448: Is a semi-specific and widely distributed form of immunity. It is defined as the first line of defense against pathogens, representing a critical systemic response to prevent infection and maintain homeostasis, contributing to the activation of an adaptive immune response. It does not adapt to specific external stimulus or a prior infection, but relies on genetically encoded recognition of particular patterns. Adaptive or acquired immunity

2223-401: Is a short-term immunization induced by the transfer of antibodies, which can be administered in several forms; as human or animal blood plasma, as pooled human immunoglobulin for intravenous ( IVIG ) or intramuscular (IG) use, and in the form of monoclonal antibodies (MAb). Passive transfer is used prophylactically in the case of immunodeficiency diseases, such as hypogammaglobulinemia . It

2340-409: Is a transient immunodepression, where the number of circulating lymphocytes decreases and antibody production declines. This may give rise to a window of opportunity for infection and reactivation of latent virus infections, but the evidence is inconclusive. During exercise there is an increase in circulating white blood cells of all types. This is caused by the frictional force of blood flowing on

2457-478: Is acquired through the exposure to a pathogen, which triggers the production of antibodies by the immune system. Passive immunity is acquired through the transfer of antibodies or activated T-cells derived from an immune host either artificially or through the placenta; it is short-lived, requiring booster doses for continued immunity. The diagram below summarizes these divisions of immunity. Adaptive immunity recognizes more diverse patterns. Unlike innate immunity it

SECTION 20

#1732856035076

2574-446: Is activated by complement binding to antibodies that have attached to these microbes or the binding of complement proteins to carbohydrates on the surfaces of microbes . This recognition signal triggers a rapid killing response. The speed of the response is a result of signal amplification that occurs after sequential proteolytic activation of complement molecules, which are also proteases. After complement proteins initially bind to

2691-527: Is affected by sleep and rest, and sleep deprivation is detrimental to immune function. Complex feedback loops involving cytokines , such as interleukin-1 and tumor necrosis factor-α produced in response to infection, appear to also play a role in the regulation of non-rapid eye movement ( REM ) sleep. Thus the immune response to infection may result in changes to the sleep cycle, including an increase in slow-wave sleep relative to REM sleep. In people with sleep deprivation, active immunizations may have

2808-470: Is also found in the epic poem " Pharsalia " written around 60 BC by the poet Marcus Annaeus Lucanus to describe a North African tribe's resistance to snake venom . The first clinical description of immunity which arose from a specific disease-causing organism is probably A Treatise on Smallpox and Measles ("Kitab fi al-jadari wa-al-hasbah″, translated 1848) written by the Islamic physician Al-Razi in

2925-502: Is also recognized by the helper cell's CD4 co-receptor, which recruits molecules inside the T cell (such as Lck ) that are responsible for the T cell's activation. Helper T cells have a weaker association with the MHC:antigen complex than observed for killer T cells, meaning many receptors (around 200–300) on the helper T cell must be bound by an MHC:antigen to activate the helper cell, while killer T cells can be activated by engagement of

3042-459: Is also said to have sought to create a 'universal antidote' to protect him from all poisons. For nearly 2000 years, poisons were thought to be the proximate cause of disease, and a complicated mixture of ingredients, called Mithridate , was used to cure poisoning during the Renaissance . An updated version of this cure, Theriacum Andromachi , was used well into the 19th century. The term "immunes"

3159-439: Is also used in the treatment of several types of acute infection, and to treat poisoning . Immunity derived from passive immunization lasts for only a short period of time, and there is also a potential risk for hypersensitivity reactions, and serum sickness , especially from gamma globulin of non-human origin. The artificial induction of passive immunity has been used for over a century to treat infectious disease, and before

3276-549: Is an immune response that damages the body's own tissues. It is divided into four classes (Type I – IV) based on the mechanisms involved and the time course of the hypersensitive reaction. Type I hypersensitivity is an immediate or anaphylactic reaction, often associated with allergy. Symptoms can range from mild discomfort to death. Type I hypersensitivity is mediated by IgE , which triggers degranulation of mast cells and basophils when cross-linked by antigen. Type II hypersensitivity occurs when antibodies bind to antigens on

3393-415: Is an important feature of cellular innate immunity performed by cells called phagocytes that engulf pathogens or particles. Phagocytes generally patrol the body searching for pathogens, but can be called to specific locations by cytokines. Once a pathogen has been engulfed by a phagocyte, it becomes trapped in an intracellular vesicle called a phagosome , which subsequently fuses with another vesicle called

3510-411: Is associated with memory of the pathogen. For thousands of years mankind has been intrigued with the causes of disease and the concept of immunity. The prehistoric view was that disease was caused by supernatural forces, and that illness was a form of theurgic punishment for "bad deeds" or "evil thoughts" visited upon the soul by the gods or by one's enemies. In Classical Greek times, Hippocrates , who

3627-721: Is encountered. Both innate and adaptive immunity depend on the ability of the immune system to distinguish between self and non-self molecules . In immunology, self molecules are components of an organism's body that can be distinguished from foreign substances by the immune system. Conversely, non-self molecules are those recognized as foreign molecules. One class of non-self molecules are called antigens (originally named for being anti body gen erators) and are defined as substances that bind to specific immune receptors and elicit an immune response. Several barriers protect organisms from infection, including mechanical, chemical, and biological barriers. The waxy cuticle of most leaves,

Immunity (medicine) - Misplaced Pages Continue

3744-530: Is mediated by transmembrane proteins known as toll-like receptors (TLRs). TLRs share a typical structural motif, the leucine rich repeats (LRRs) , which give them a curved shape. Toll-like receptors were first discovered in Drosophila and trigger the synthesis and secretion of cytokines and activation of other host defense programs that are necessary for both innate or adaptive immune responses. Ten toll-like receptors have been described in humans. Cells in

3861-399: Is one of the first responses of the immune system to infection, but it can appear without known cause. Mithridate Mithridate , also known as mithridatium , mithridatum , or mithridaticum , is a semi-mythical remedy with as many as 65 ingredients, used as an antidote for poisoning , and said to have been created by Mithridates VI Eupator of Pontus in the 1st century BC. It

3978-503: Is rarely used in humans because it requires histocompatible (matched) donors, which are often difficult to find. In unmatched donors this type of transfer carries severe risks of graft versus host disease . It has, however, been used to treat certain diseases including some types of cancer and immunodeficiency . This type of transfer differs from a bone marrow transplant , in which (undifferentiated) hematopoietic stem cells are transferred. When B cells and T cells are activated by

4095-545: Is regarded as the Father of Medicine, diseases were attributed to an alteration or imbalance in one of the four humors (blood, phlegm, yellow bile or black bile). The first written descriptions of the concept of immunity may have been made by the Athenian Thucydides who, in 430 BC, described that when the plague hit Athens : "the sick and the dying were tended by the pitying care of those who had recovered, because they knew

4212-555: Is required for defense of tuberculosis in humans. Individuals with genetic defects in TNF may get recurrent and life-threatening infections with tuberculosis bacteria ( Mycobacterium tuberculosis ) but are otherwise healthy. They also seem to respond to other infections more or less normally. The condition is therefore called Mendelian susceptibility to mycobacterial disease (MSMD) and variants of it can be caused by other genes related to interferon production or signaling (e.g. by mutations in

4329-603: Is said to have so fortified his body against poisons with antidotes and preservatives that when he tried to kill himself, he could not find any poison that would have an effect, and, according to some legends, had to ask a soldier to run him through with a sword. The recipe for the reputed antidote was found in his cabinet, written with his own hand, and was carried to Rome by Pompey . It was translated into Latin by Pompey's freedman Lenaeus, and later improved upon by Nero 's physician Andromachus and Marcus Aurelius ' physician Galen . It likely underwent considerable alterations since

4446-578: Is sufficient." Of these ingredients, Illyrian iris, darnel, and rhubarb were not commonly found in other versions of the antidote. However, Celsus' formulation, written 100 years after the death of Mithridates, was one of the first published. Galen called the antidote " theriac " and presented versions by Aelius (used by Julius Caesar), Andromachus (physician to Nero), Antipater, Nicostratus, and Damocratis. The Andromachus formulation closely resembles that of Celsus. The manufacture of antidotes called mithridate or theriac (English "treacle") continued into

4563-592: Is the active component of the host immune response, mediated by antigen-specific lymphocytes . Unlike the innate immunity, the acquired immunity is highly specific to a particular pathogen, including the development of immunological memory . Like the innate system, the acquired system includes both humoral immunity components and cell-mediated immunity components. Adaptive immunity can be acquired either 'naturally' (by infection) or 'artificially' (through deliberate actions such as vaccination). Adaptive immunity can also be classified as 'active' or 'passive'. Active immunity

4680-421: Is the only antibody isotype that can pass through the placenta. Passive immunity is also provided through the transfer of IgA antibodies found in breast milk that are transferred to the gut of a nursing infant, protecting against bacterial infections, until the newborn can synthesize its antibodies. Colostrum present in mothers milk is an example of passive immunity. Artificially acquired passive immunity

4797-430: Is thought to have assumed that those animals acquired some detoxifying property, so that their blood would contain transformed components of the snake venom that could induce resistance to it instead of exerting a toxic effect. Mithridates reasoned that, by drinking the blood of these animals, he could acquire a similar resistance. Fearing assassination by poison, he took daily sub-lethal doses of venom to build tolerance. He

Immunity (medicine) - Misplaced Pages Continue

4914-504: Is to generate active forms of the inflammatory cytokines IL-1β and IL-18. The complement system is a biochemical cascade that attacks the surfaces of foreign cells. It contains over 20 different proteins and is named for its ability to "complement" the killing of pathogens by antibodies . Complement is the major humoral component of the innate immune response. Many species have complement systems, including non- mammals like plants, fish, and some invertebrates . In humans, this response

5031-402: The "professional" phagocytes ( macrophages , neutrophils , and dendritic cells ). These cells identify and eliminate pathogens, either by attacking larger pathogens through contact or by engulfing and then killing microorganisms. The other cells involved in the innate response include innate lymphoid cells , mast cells , eosinophils , basophils , and natural killer cells . Phagocytosis

5148-542: The Centers for Disease Control and Prevention (CDC) concluded that "Multiple studies in different settings have consistently shown that infection with SARS-CoV-2 and vaccination each result in a low risk of subsequent infection with antigenically similar variants for at least 6 months. Numerous immunologic studies and a growing number of epidemiologic studies have shown that vaccinating previously infected individuals significantly enhances their immune response and effectively reduces

5265-483: The antitoxin became the first major success of modern therapeutic immunology. In Europe , the induction of active immunity emerged in an attempt to contain smallpox . Immunization has existed in various forms for at least a thousand years, without the terminology. The earliest use of immunization is unknown, but, about 1000 AD, the Chinese began practicing a form of immunization by drying and inhaling powders derived from

5382-573: The endothelial cell surface and catecholamines affecting β-adrenergic receptors (βARs). The number of neutrophils in the blood increases and remains raised for up to six hours and immature forms are present. Although the increase in neutrophils (" neutrophilia ") is similar to that seen during bacterial infections, after exercise the cell population returns to normal by around 24 hours. The number of circulating lymphocytes (mainly natural killer cells ) decreases during intense exercise but returns to normal after 4 to 6 hours. Although up to 2% of

5499-449: The exoskeleton of insects, the shells and membranes of externally deposited eggs, and skin are examples of mechanical barriers that are the first line of defense against infection. Organisms cannot be completely sealed from their environments, so systems act to protect body openings such as the lungs , intestines , and the genitourinary tract . In the lungs, coughing and sneezing mechanically eject pathogens and other irritants from

5616-458: The innate immune system , such as dendritic cells, macrophages, monocytes, neutrophils, and epithelial cells, to identify two classes of molecules: pathogen-associated molecular patterns (PAMPs), which are associated with microbial pathogens , and damage-associated molecular patterns (DAMPs), which are associated with components of host's cells that are released during cell damage or cell death. Recognition of extracellular or endosomal PAMPs

5733-492: The lymphoid lineage . These cells are defined by the absence of antigen-specific B- or T-cell receptor (TCR) because of the lack of recombination activating gene . ILCs do not express myeloid or dendritic cell markers. Natural killer cells (NK cells) are lymphocytes and a component of the innate immune system that does not directly attack invading microbes. Rather, NK cells destroy compromised host cells, such as tumor cells or virus-infected cells, recognizing such cells by

5850-627: The nervous systems. The immune system also plays a crucial role in embryogenesis (development of the embryo), as well as in tissue repair and regeneration . Hormones can act as immunomodulators , altering the sensitivity of the immune system. For example, female sex hormones are known immunostimulators of both adaptive and innate immune responses. Some autoimmune diseases such as lupus erythematosus strike women preferentially, and their onset often coincides with puberty . By contrast, male sex hormones such as testosterone seem to be immunosuppressive . Other hormones appear to regulate

5967-514: The respiratory tract . The flushing action of tears and urine also mechanically expels pathogens, while mucus secreted by the respiratory and gastrointestinal tract serves to trap and entangle microorganisms . Chemical barriers also protect against infection. The skin and respiratory tract secrete antimicrobial peptides such as the β- defensins . Enzymes such as lysozyme and phospholipase A2 in saliva , tears, and breast milk are also antibacterials . Vaginal secretions serve as

SECTION 50

#1732856035076

6084-489: The 9th century. In the treatise, Al Razi describes the clinical presentation of smallpox and measles and goes on to indicate that exposure to these specific agents confers lasting immunity (although he does not use this term). Until the 19th century, the miasma theory was also widely accepted. The theory viewed diseases such as cholera or the Black Plague as being caused by a miasma, a noxious form of "bad air". If someone

6201-399: The B cell surface and recognizes native (unprocessed) antigen without any need for antigen processing . Such antigens may be large molecules found on the surfaces of pathogens, but can also be small haptens (such as penicillin) attached to carrier molecule. Each lineage of B cell expresses a different antibody, so the complete set of B cell antigen receptors represent all the antibodies that

6318-587: The T cell's surface, such as CD40 ligand (also called CD154 ), which provide extra stimulatory signals typically required to activate antibody-producing B cells. Gamma delta T cells (γδ T cells) possess an alternative T-cell receptor (TCR) as opposed to CD4+ and CD8+ (αβ) T cells and share the characteristics of helper T cells, cytotoxic T cells and NK cells. The conditions that produce responses from γδ T cells are not fully understood. Like other 'unconventional' T cell subsets bearing invariant TCRs, such as CD1d -restricted natural killer T cells , γδ T cells straddle

6435-411: The ability to adapt to recognize pathogens more efficiently. Adaptive (or acquired) immunity creates an immunological memory leading to an enhanced response to subsequent encounters with that same pathogen. This process of acquired immunity is the basis of vaccination . Dysfunction of the immune system can cause autoimmune diseases , inflammatory diseases and cancer . Immunodeficiency occurs when

6552-440: The advent of antibiotics , was often the only specific treatment for certain infections. Immunoglobulin therapy continued to be a first line therapy in the treatment of severe respiratory diseases until the 1930s, even after sulfonamide lot antibiotics were introduced. Passive or " adoptive transfer " of cell-mediated immunity, is conferred by the transfer of "sensitized" or activated T-cells from one individual into another. It

6669-565: The antibody that recognizes this antigen. These antibodies circulate in blood plasma and lymph , bind to pathogens expressing the antigen and mark them for destruction by complement activation or for uptake and destruction by phagocytes . Antibodies can also neutralize challenges directly, by binding to bacterial toxins or by interfering with the receptors that viruses and bacteria use to infect cells. Newborn infants have no prior exposure to microbes and are particularly vulnerable to infection. Several layers of passive protection are provided by

6786-518: The antidote in De Medicina (ca. AD 30). A recent translation is as follows: "But the most famous antidote is that of Mithridates, which that king is said to have taken daily and by it to have rendered his body safe against danger from poison". It contained: The ingredients are then "pounded and taken up in honey . Against poisoning, a piece the size of an almond is given in wine. In other affections an amount corresponding in size to an Egyptian bean

6903-437: The antidote incorporated dried blood or the dried flesh of lizards or vipers or Malabathrum . Pliny ( Natural History , XXIX.24–25, ca. AD 77) was skeptical of mithridate and other such theriacs (panacea potions), with their numerous ingredients: The Mithridatic antidote is composed of fifty-four ingredients, no two of them having the same weight, while of some is prescribed one sixtieth part of one denarius. Which of

7020-453: The body can manufacture. When B or T cells encounter their related antigens they multiply and many "clones" of the cells are produced that target the same antigen. This is called clonal selection . Both B cells and T cells carry receptor molecules that recognize specific targets. T cells recognize a "non-self" target, such as a pathogen, only after antigens (small fragments of the pathogen) have been processed and presented in combination with

7137-429: The body does not develop memory, therefore the patient is at risk of being infected by the same pathogen later. A fetus naturally acquires passive immunity from its mother during pregnancy. Maternal passive immunity is antibody -mediated immunity. The mother's antibodies (MatAb) are passed through the placenta to the fetus by an FcRn receptor on placental cells. This occurs around the third month of gestation . IgG

SECTION 60

#1732856035076

7254-585: The body in pursuit of invading pathogens. Neutrophils are normally found in the bloodstream and are the most abundant type of phagocyte, representing 50% to 60% of total circulating leukocytes. During the acute phase of inflammation , neutrophils migrate toward the site of inflammation in a process called chemotaxis and are usually the first cells to arrive at the scene of infection. Macrophages are versatile cells that reside within tissues and produce an array of chemicals including enzymes, complement proteins , and cytokines. They can also act as scavengers that rid

7371-440: The body of worn-out cells and other debris and as antigen-presenting cells (APCs) that activate the adaptive immune system. Dendritic cells are phagocytes in tissues that are in contact with the external environment; therefore, they are located mainly in the skin, nose, lungs, stomach, and intestines. They are named for their resemblance to neuronal dendrites , as both have many spine-like projections. Dendritic cells serve as

7488-654: The border between innate and adaptive immunity. On one hand, γδ T cells are a component of adaptive immunity as they rearrange TCR genes to produce receptor diversity and can also develop a memory phenotype. On the other hand, the various subsets are also part of the innate immune system, as restricted TCR or NK receptors may be used as pattern recognition receptors . For example, large numbers of human Vγ9/Vδ2 T cells respond within hours to common molecules produced by microbes, and highly restricted Vδ1+ T cells in epithelia respond to stressed epithelial cells. A B cell identifies pathogens when antibodies on its surface bind to

7605-776: The brakes on NK cells. Inflammation is one of the first responses of the immune system to infection. The symptoms of inflammation are redness, swelling, heat, and pain, which are caused by increased blood flow into tissue. Inflammation is produced by eicosanoids and cytokines , which are released by injured or infected cells. Eicosanoids include prostaglandins that produce fever and the dilation of blood vessels associated with inflammation and leukotrienes that attract certain white blood cells (leukocytes). Common cytokines include interleukins that are responsible for communication between white blood cells; chemokines that promote chemotaxis ; and interferons that have antiviral effects, such as shutting down protein synthesis in

7722-520: The cells die most migrate from the blood to the tissues, mainly the intestines and lungs, where pathogens are most likely to be encountered. Some monocytes leave the blood circulation and migrate to the muscles where they differentiate and become macrophages . These cells differentiate into two types: proliferative macrophages, which are responsible for increasing the number of stem cells and restorative macrophages, which are involved their maturing to muscle cells. The immune system, particularly

7839-653: The components of the immune system are inactive. The ability of the immune system to respond to pathogens is diminished in both the young and the elderly , with immune responses beginning to decline at around 50 years of age due to immunosenescence . In developed countries , obesity , alcoholism , and drug use are common causes of poor immune function, while malnutrition is the most common cause of immunodeficiency in developing countries . Diets lacking sufficient protein are associated with impaired cell-mediated immunity, complement activity, phagocyte function, IgA antibody concentrations, and cytokine production. Additionally,

7956-589: The conditions in their environment, such as pH or available iron. As a result, the probability that pathogens will reach sufficient numbers to cause illness is reduced. Microorganisms or toxins that successfully enter an organism encounter the cells and mechanisms of the innate immune system. The innate response is usually triggered when microbes are identified by pattern recognition receptors , which recognize components that are conserved among broad groups of microorganisms, or when damaged, injured or stressed cells send out alarm signals, many of which are recognized by

8073-410: The course of the disease and were themselves free from apprehensions. For no one was ever attacked a second time, or not with a fatal result". Active immunotherapy may have begun with Mithridates VI of Pontus (120-63 BC) who, to induce active immunity for snake venom, recommended using a method similar to modern toxoid serum therapy , by drinking the blood of animals which fed on venomous snakes. He

8190-551: The crusts of smallpox lesions. Around the 15th century in India , the Ottoman Empire , and east Africa , the practice of inoculation (poking the skin with powdered material derived from smallpox crusts) was quite common. This practice was first introduced into the west in 1721 by Lady Mary Wortley Montagu [the phrase "first introduced into the west in 1721 by lady Montagu" is quite not accurate and should be rendered "first promoted in

8307-404: The different roles of the two types of T cell. A third, minor subtype are the γδ T cells that recognize intact antigens that are not bound to MHC receptors. The double-positive T cells are exposed to a wide variety of self-antigens in the thymus , in which iodine is necessary for its thymus development and activity. In contrast, the B cell antigen-specific receptor is an antibody molecule on

8424-445: The disease. The term vaccination was coined by Richard Dunning, a colleague of Edward Jenner , and adapted by Louis Pasteur for his pioneering work in vaccination. The method Pasteur used entailed treating the infectious agents for those diseases, so they lost the ability to cause serious disease. Pasteur adopted the name vaccine as a generic term in honor of Jenner's discovery, which Pasteur's work built upon. In 1807, Bavaria became

8541-455: The far safer method of deliberate infection with cowpox virus, ( smallpox vaccine ), which caused a mild infection that also induced immunity to smallpox. By 1800, the procedure was referred to as vaccination . To avoid confusion, smallpox inoculation was increasingly referred to as variolation , and it became common practice to use this term without regard for chronology. The success and general acceptance of Jenner's procedure would later drive

8658-525: The first group to require their military recruits to be vaccinated against smallpox, as the spread of smallpox was linked to combat. Subsequently, the practice of vaccination would increase with the spread of war. There are four types of traditional vaccines : In addition, there are some newer types of vaccines in use: A variety of vaccine types are under development; see Experimental Vaccine Types . Most vaccines are given by hypodermic or intramuscular injection as they are not absorbed reliably through

8775-465: The foetus through the placenta, and can also be induced artificially, when high levels of human (or horse ) antibodies specific for a pathogen or toxin are transferred to non- immune individuals. Passive immunization is used when there is a high risk of infection and insufficient time for the body to develop its own immune response, or to reduce the symptoms of ongoing or immunosuppressive diseases. Passive immunity provides immediate protection, but

8892-431: The formation of a membrane attack complex . The adaptive immune system evolved in early vertebrates and allows for a stronger immune response as well as immunological memory , where each pathogen is "remembered" by a signature antigen. The adaptive immune response is antigen-specific and requires the recognition of specific "non-self" antigens during a process called antigen presentation . Antigen specificity allows for

9009-419: The functions of specialized cells (located in the thymus and bone marrow) is to present young lymphocytes with self antigens produced throughout the body and to eliminate those cells that recognize self-antigens , preventing autoimmunity. Common autoimmune diseases include Hashimoto's thyroiditis , rheumatoid arthritis , diabetes mellitus type 1 , and systemic lupus erythematosus . Hypersensitivity

9126-490: The general nature of vaccination developed by Pasteur and others towards the end of the 19th century. In 1891, Pasteur widened the definition of vaccine in honour of Jenner, and it then became essential to qualify the term by referring to polio vaccine , measles vaccine etc. Passive immunity is the immunity acquired by the transfer of ready-made antibodies from one individual to another. Passive immunity can occur naturally, such as when maternal antibodies are transferred to

9243-420: The generation of responses that are tailored to specific pathogens or pathogen-infected cells. The ability to mount these tailored responses is maintained in the body by "memory cells". Should a pathogen infect the body more than once, these specific memory cells are used to quickly eliminate it. The cells of the adaptive immune system are special types of leukocytes, called lymphocytes. B cells and T cells are

9360-560: The genes IFNG , IL12B , IL12RB1 , IL12RB2 , IL23R , ISG15 , MCTS1 , RORC , TBX21 , TYK2 , CYBB , JAK1 , IFNGR1 , IFNGR2 , STAT1 , USP18 , IRF1 , IRF8 , NEMO , SPPL2A ). Immune system The immune system is a network of biological systems that protects an organism from diseases . It detects and responds to a wide variety of pathogens , from viruses to bacteria , as well as cancer cells , parasitic worms , and also objects such as wood splinters , distinguishing them from

9477-611: The gods, in the name of Truth, fixed these absurd proportions? No human brain could have been sharp enough. It is plainly a showy parade of the art, and a colossal boast of science. In A. E. Housman 's collection of poetry titled A Shropshire Lad published in 1896, there is a poem about King Mithridates and his antidote's amazing abilities: There was a king reigned in the East: There, when kings will sit to feast, They get their fill before they think With poisoned meat and poisoned drink. He gathered all that springs to birth From

9594-472: The gut. Live attenuated polio and some typhoid and cholera vaccines are given orally in order to produce immunity based in the bowel . Hybrid immunity is the combination of natural immunity and artificial immunity. Studies of hybrid-immune people found that their blood was better able to neutralize the Beta and other variants of SARS-CoV-2 than never-infected, vaccinated people. Moreover, on 29 October 2021,

9711-527: The host cell. Growth factors and cytotoxic factors may also be released. These cytokines and other chemicals recruit immune cells to the site of infection and promote the healing of any damaged tissue following the removal of pathogens. The pattern-recognition receptors called inflammasomes are multiprotein complexes (consisting of an NLR, the adaptor protein ASC, and the effector molecule pro-caspase-1) that form in response to cytosolic PAMPs and DAMPs, whose function

9828-635: The immune system as well, most notably prolactin , growth hormone and vitamin D . Although cellular studies indicate that vitamin D has receptors and probable functions in the immune system, there is no clinical evidence to prove that vitamin D deficiency increases the risk for immune diseases or vitamin D supplementation lowers immune disease risk. A 2011 United States Institute of Medicine report stated that "outcomes related to ... immune functioning and autoimmune disorders , and infections ... could not be linked reliably with calcium or vitamin D intake and were often conflicting." The immune system

9945-588: The immune system is less active than normal, resulting in recurring and life-threatening infections. In humans, immunodeficiency can be the result of a genetic disease such as severe combined immunodeficiency , acquired conditions such as HIV / AIDS , or the use of immunosuppressive medication . Autoimmunity results from a hyperactive immune system attacking normal tissues as if they were foreign organisms. Common autoimmune diseases include Hashimoto's thyroiditis , rheumatoid arthritis , diabetes mellitus type 1 , and systemic lupus erythematosus . Immunology covers

10062-699: The individual's own cells, marking them for destruction. This is also called antibody-dependent (or cytotoxic) hypersensitivity, and is mediated by IgG and IgM antibodies. Immune complexes (aggregations of antigens, complement proteins, and IgG and IgM antibodies) deposited in various tissues trigger Type III hypersensitivity reactions. Type IV hypersensitivity (also known as cell-mediated or delayed type hypersensitivity ) usually takes between two and three days to develop. Type IV reactions are involved in many autoimmune and infectious diseases, but may also involve contact dermatitis . These reactions are mediated by T cells , monocytes , and macrophages . Inflammation

10179-425: The inflammatory response. They are most often associated with allergy and anaphylaxis . Basophils and eosinophils are related to neutrophils. They secrete chemical mediators that are involved in defending against parasites and play a role in allergic reactions, such as asthma . Innate lymphoid cells (ILCs) are a group of innate immune cells that are derived from common lymphoid progenitor and belong to

10296-497: The initiation of Th1 immune responses. During wake periods, differentiated effector cells, such as cytotoxic natural killer cells and cytotoxic T lymphocytes, peak to elicit an effective response against any intruding pathogens. Anti-inflammatory molecules, such as cortisol and catecholamines , also peak during awake active times. Inflammation would cause serious cognitive and physical impairments if it were to occur during wake times, and inflammation may occur during sleep times due to

10413-437: The innate and adaptive immune responses and help determine which immune responses the body makes to a particular pathogen. These cells have no cytotoxic activity and do not kill infected cells or clear pathogens directly. They instead control the immune response by directing other cells to perform these tasks. Helper T cells express T cell receptors that recognize antigen bound to Class II MHC molecules. The MHC:antigen complex

10530-886: The innate component, plays a decisive role in tissue repair after an insult . Key actors include macrophages and neutrophils , but other cellular actors, including γδ T cells , innate lymphoid cells (ILCs), and regulatory T cells (Tregs), are also important. The plasticity of immune cells and the balance between pro-inflammatory and anti-inflammatory signals are crucial aspects of efficient tissue repair. Immune components and pathways are involved in regeneration as well, for example in amphibians such as in axolotl limb regeneration . According to one hypothesis, organisms that can regenerate ( e.g. , axolotls ) could be less immunocompetent than organisms that cannot regenerate. Failures of host defense occur and fall into three broad categories: immunodeficiencies, autoimmunity, and hypersensitivities. Immunodeficiencies occur when one or more of

10647-433: The innate immune system have pattern recognition receptors, which detect infection or cell damage, inside. Three major classes of these "cytosolic" receptors are NOD–like receptors , RIG (retinoic acid-inducible gene)-like receptors , and cytosolic DNA sensors. Some leukocytes (white blood cells) act like independent, single-celled organisms and are the second arm of the innate immune system. The innate leukocytes include

10764-473: The innate response, vertebrates possess a second layer of protection, the adaptive immune system , which is activated by the innate response. Here, the immune system adapts its response during an infection to improve its recognition of the pathogen. This improved response is then retained after the pathogen has been eliminated, in the form of an immunological memory , and allows the adaptive immune system to mount faster and stronger attacks each time this pathogen

10881-423: The lifetime of an animal, these memory cells remember each specific pathogen encountered and can mount a strong response if the pathogen is detected again. T-cells recognize pathogens by small protein-based infection signals, called antigens, that bind to directly to T-cell surface receptors. B-cells use the protein, immunoglobulin, to recognize pathogens by their antigens. This is "adaptive" because it occurs during

10998-415: The lifetime of an individual as an adaptation to infection with that pathogen and prepares the immune system for future challenges. Immunological memory can be in the form of either passive short-term memory or active long-term memory. The immune system is involved in many aspects of physiological regulation in the body. The immune system interacts intimately with other systems, such as the endocrine and

11115-459: The loss of the thymus at an early age through genetic mutation or surgical removal results in severe immunodeficiency and a high susceptibility to infection. Immunodeficiencies can also be inherited or ' acquired '. Severe combined immunodeficiency is a rare genetic disorder characterized by the disturbed development of functional T cells and B cells caused by numerous genetic mutations. Chronic granulomatous disease , where phagocytes have

11232-454: The major types of lymphocytes and are derived from hematopoietic stem cells in the bone marrow . B cells are involved in the humoral immune response , whereas T cells are involved in cell-mediated immune response . Killer T cells only recognize antigens coupled to Class I MHC molecules, while helper T cells and regulatory T cells only recognize antigens coupled to Class II MHC molecules. These two mechanisms of antigen presentation reflect

11349-409: The many-venomed earth; First a little, thence to more, He sampled all her killing store; And easy, smiling, seasoned sound, Sate the king when healths went round. They put arsenic in his meat And stared aghast to watch him eat; They poured strychnine in his cup And shook to see him drink it up: They shook, they stared as white's their shirt: Them it was their poison hurt. —I tell

11466-509: The microbe, they activate their protease activity, which in turn activates other complement proteases, and so on. This produces a catalytic cascade that amplifies the initial signal by controlled positive feedback . The cascade results in the production of peptides that attract immune cells, increase vascular permeability , and opsonize (coat) the surface of a pathogen, marking it for destruction. This deposition of complement can also kill cells directly by disrupting their plasma membrane via

11583-408: The milieu of hormones produced at this time (leptin, pituitary growth hormone, and prolactin) supports the interactions between APCs and T-cells, a shift of the T h 1/T h 2 cytokine balance towards one that supports T h 1, an increase in overall T h cell proliferation, and naïve T cell migration to lymph nodes. This is also thought to support the formation of long-lasting immune memory through

11700-412: The mother. During pregnancy, a particular type of antibody, called IgG , is transported from mother to baby directly through the placenta , so human babies have high levels of antibodies even at birth, with the same range of antigen specificities as their mother. Breast milk or colostrum also contains antibodies that are transferred to the gut of the infant and protect against bacterial infections until

11817-462: The negative consequences of sleep deprivation, sleep and the intertwined circadian system have been shown to have strong regulatory effects on immunological functions affecting both innate and adaptive immunity. First, during the early slow-wave-sleep stage, a sudden drop in blood levels of cortisol , epinephrine , and norepinephrine causes increased blood levels of the hormones leptin , pituitary growth hormone , and prolactin . These signals induce

11934-506: The newborn can synthesize its own antibodies. This is passive immunity because the fetus does not actually make any memory cells or antibodies—it only borrows them. This passive immunity is usually short-term, lasting from a few days up to several months. In medicine, protective passive immunity can also be transferred artificially from one individual to another. When B cells and T cells are activated and begin to replicate, some of their offspring become long-lived memory cells. Throughout

12051-591: The nineteenth century. Ephraim Chambers , in his 1728 Cyclopaedia , says "Mithridate is one of the capital Medicines in the Apothecaries Shops, being composed of a vast Number of Drugs, as Opium , Myrrh , Agaric , Saffron , Ginger , Cinnamon , Spikenard , Frankincense , Castor , Pepper , Gentian , &c. It is accounted a Cordial , Opiate , Sudorific , and Alexipharmic ". Petrus Andreas Matthiolus considered it more effectual against poisons than Venice treacle , and easier to make. Late versions of

12168-443: The non-reaction to self substances is described as immunity. The two components of the immune system create a dynamic biological environment where "health" can be seen as a physical state where the self is immunologically spared, and what is foreign is inflammatorily and immunologically eliminated. "Disease" can arise when what is foreign cannot be eliminated or what is self is not spared. Innate immunity, also known as native immunity,

12285-475: The organism's own healthy tissue . Many species have two major subsystems of the immune system. The innate immune system provides a preconfigured response to broad groups of situations and stimuli. The adaptive immune system provides a tailored response to each stimulus by learning to recognize molecules it has previously encountered. Both use molecules and cells to perform their functions. Nearly all organisms have some kind of immune system. Bacteria have

12402-434: The presence of melatonin . Inflammation causes a great deal of oxidative stress and the presence of melatonin during sleep times could actively counteract free radical production during this time. Physical exercise has a positive effect on the immune system and depending on the frequency and intensity, the pathogenic effects of diseases caused by bacteria and viruses are moderated. Immediately after intense exercise there

12519-501: The risk of subsequent infection, including in the setting of increased circulation of more infectious variants. ..." Immunity is determined genetically. Genomes in humans and animals encode the antibodies and numerous other immune response genes. While many of these genes are generally required for active and passive immune responses (see sections above), there are also many genes that appear to be required for very specific immune responses. For instance, Tumor Necrosis Factor (TNF)

12636-532: The same receptors as those that recognize pathogens. Innate immune defenses are non-specific, meaning these systems respond to pathogens in a generic way. This system does not confer long-lasting immunity against a pathogen. The innate immune system is the dominant system of host defense in most organisms, and the only one in plants. Cells in the innate immune system use pattern recognition receptors to recognize molecular structures that are produced by pathogens. They are proteins expressed, mainly, by cells of

12753-447: The study of all aspects of the immune system. The immune system protects its host from infection with layered defenses of increasing specificity. Physical barriers prevent pathogens such as bacteria and viruses from entering the organism. If a pathogen breaches these barriers, the innate immune system provides an immediate, but non-specific response. Innate immune systems are found in all animals . If pathogens successfully evade

12870-503: The target cell's plasma membrane , allowing ions , water and toxins to enter. The entry of another toxin called granulysin (a protease) induces the target cell to undergo apoptosis . T cell killing of host cells is particularly important in preventing the replication of viruses. T cell activation is tightly controlled and generally requires a very strong MHC/antigen activation signal, or additional activation signals provided by "helper" T cells (see below). Helper T cells regulate both

12987-458: The throne. Supposedly during his youth he began to suspect plots against him at his mother's orders and was aware of her likely connection with his father's death. He then, supposedly, began to notice pains during his meals, and suspected his mother had ordered small amounts of poison to be added to his food in order to cause his health to deteriorate while avoiding notice of intent to kill him slowly. After other assassination attempts, he fled into

13104-704: The time of Mithridates. After realizing the anti-toxic effects of snake meat, Andromachus made Faroug antidote with changes in the previous formulas. In the Middle Ages , mithridate was also used as part of a regimen to ward off potential threats of plague . According to Simon Kellwaye (1593), one should "take a great Onyon , make a hole in the myddle of him, then fill the place with Mitridat or Triacle , and some leaues of Rue ". Until as late as 1786, physicians in London were officially prescribing mithridate. According to historian Christopher Hill , Oliver Cromwell took

13221-649: The west, by lady Montague, in 1721". Because, as you can read here https://en.wikipedia.org/wiki/Variolation , the procedure was already known in Wales: "The method was first used in China, India, parts of Africa and the Middle East before it was introduced into England and North America in the 1720s in the face of some opposition. However, inoculation had been reported in Wales since the early 17th century"]. In 1798, Edward Jenner introduced

13338-408: The wilderness. While in the wild it is said that he began consuming non-lethal levels of poisons and mixing many into a remedy to make him immune to many poisons. In keeping with most medical practices of his era, Mithridates' anti-poison routines included a religious component supervised by Agari , or Scythian shamans who never left his side. Aulus Cornelius Celsus details one version of

13455-455: Was exposed to the miasma in a swamp, in evening air, or breathing air in a sickroom or hospital ward, they could catch a disease. Since the 19th century, communicable diseases came to be viewed as being caused by germs/microbes. The modern word "immunity" derives from the Latin immunis, meaning exemption from military service, tax payments or other public services. The first scientist who developed

13572-422: Was not discovered until later. This type of immunity is both active and adaptive because the body's immune system prepares itself for future challenges. Active immunity often involves both the cell-mediated and humoral aspects of immunity as well as input from the innate immune system . Naturally acquired active immunity occurs as the result of an infection. When a person is exposed to a live pathogen and develops

13689-464: Was one of the most complex and highly sought-after drugs during the Middle Ages and the Renaissance , particularly in Italy and France, where it was in continual use for centuries. An updated recipe called theriac ( Theriacum Andromachi ) was known well into the 19th century. Mithridate takes its name from its inventor, Mithridates VI, king of the ancient Anatolian Kingdom of Pontus (134 to 63 BC), who

#75924