1.
Scanning electron microscope
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A scanning electron microscope is a type of electron microscope that produces images of a sample by scanning it with a focused beam of electrons. The electrons interact with atoms in the sample, producing various signals that contain information about the surface topography. The electron beam is scanned in a raster scan pattern. SEM can achieve better than 1 nanometer. Specimens can be observed in vacuum, in low vacuum, in wet conditions. The most common SEM mode is detection of electrons emitted by atoms excited by the electron beam. The number of electrons that can be detected depends, among other things. By scanning the sample and collecting the electrons that are emitted using a special detector. An account of the history of SEM has been presented by McMullan. Ardenne applied the principle not only to achieve magnification but also to purposefully eliminate the chromatic aberration otherwise inherent in the electron microscope. He further discussed the various modes, possibilities and theory of SEM. The types of produced by an SEM include secondary electrons, reflected or back-scattered electrons, photons of characteristic X-rays and light, absorbed current. Secondary electron detectors are standard equipment in all SEMs, but it is rare that a machine would have detectors for all other possible signals. The signals result from interactions of the beam with atoms at various depths within the sample. In the most common or standard detection mode, ie secondary electron imaging or SEI, consequently, SEM can produce very high-resolution images of a sample surface, revealing details less than 1 nm in size. Back-scattered electrons are beam electrons that are reflected from the sample by elastic scattering and they emerge from deeper locations within the specimen and consequently the resolution of BSE images is generally poorer than SE images. BSE images can provide information about the distribution of different elements in the sample, characteristic X-rays are emitted when the electron beam removes an inner shell electron from the sample, causing a higher-energy electron to fill the shell and release energy. These characteristic X-rays are used to identify the composition and measure the abundance of elements in the sample, due to the very narrow electron beam, SEM micrographs have a large depth of field yielding a characteristic three-dimensional appearance useful for understanding the surface structure of a sample
2.
Organ system
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A biological system is a complex network of biologically relevant entities. On the micro to the scale, examples of biological systems are cells, organelles, macromolecular complexes. A biological system is not to be confused with a living system, for further information see e. g. definition of life or synthetic biology. These specific systems are studied in Human anatomy. Human systems are present in many other animals. Circulatory system, pumping and channeling blood to and from the body and lungs with heart, integumentary system, skin, hair, fat, and nails. Skeletal system, structural support and protection with bones, cartilage, ligaments, urinary system, kidneys, ureters, bladder and urethra involved in fluid balance, electrolyte balance and excretion of urine. Respiratory system, the used for breathing, the pharynx, larynx, bronchi, lungs. The lymphatic system includes functions including immune responses and development of antibodies, muscular system, allows for manipulation of the environment, provides locomotion, maintains posture, and produces heat. Includes skeletal muscles, smooth muscles and cardiac muscle, nervous system, collecting, transferring and processing information with brain, spinal cord and peripheral nervous system. The notion of system relies upon the concept of vital or organic function and this idea was already present in Antiquity, but the application of the term system is more reccent. Inspired in the work of Adam Smith, Milne-Edwards wrote that the body of all living beings, whether animal or plant, where the organs, comparable to workers, work incessantly to produce the phenomena that constitute the life of the individual. In more differentiated organisms, the labor could be apportioned between different instruments or systems. Synthesis and Analysis of a Biological System, by Hiroyuki Kurata,1999
3.
Immune system
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The immune system is a host defense system comprising many biological structures and processes within an organism that protects against disease. To function properly, a system must detect a wide variety of agents, known as pathogens, from viruses to parasitic worms. In many species, the system can be classified into subsystems, such as the innate immune system versus the adaptive immune system. In humans, the barrier, blood–cerebrospinal fluid barrier, and similar fluid–brain barriers separate the peripheral immune system from the neuroimmune system. Even simple unicellular organisms such as bacteria possess a rudimentary immune system in the form of enzymes that protect against bacteriophage infections, other basic immune mechanisms evolved in ancient eukaryotes and remain in their modern descendants, such as plants and invertebrates. These mechanisms include phagocytosis, antimicrobial peptides called defensins, and the complement system, jawed vertebrates, including humans, have even more sophisticated defense mechanisms, including the ability to adapt over time to recognize specific pathogens more efficiently. Adaptive immunity creates immunological memory after a response to a specific pathogen. This process of acquired immunity is the basis of vaccination, disorders of the immune system can result in autoimmune diseases, inflammatory diseases and cancer. Immunodeficiency occurs when the system is less active than normal. In humans, immunodeficiency can either be the result of a disease such as severe combined immunodeficiency, acquired conditions such as HIV/AIDS. In contrast, autoimmunity results from an immune system attacking normal tissues as if they were foreign organisms. Common autoimmune diseases include Hashimotos thyroiditis, rheumatoid arthritis, diabetes mellitus type 1, immunology covers the study of all aspects of the immune system. Immunology is a science that examines the structure and function of the immune system and it originates from medicine and early studies on the causes of immunity to disease. The earliest known reference to immunity was during the plague of Athens in 430 BC, thucydides noted that people who had recovered from a previous bout of the disease could nurse the sick without contracting the illness a second time. In the 18th century, Pierre-Louis Moreau de Maupertuis made experiments with scorpion venom and observed that certain dogs and this and other observations of acquired immunity were later exploited by Louis Pasteur in his development of vaccination and his proposed germ theory of disease. Pasteurs theory was in opposition to contemporary theories of disease. It was not until Robert Kochs 1891 proofs, for which he was awarded a Nobel Prize in 1905, viruses were confirmed as human pathogens in 1901, with the discovery of the yellow fever virus by Walter Reed. Immunology made an advance towards the end of the 19th century, through rapid developments, in the study of humoral immunity
4.
White blood cell
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White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from multipotent cells in the bone known as hematopoietic stem cells. Leukocytes are found throughout the body, including the blood and lymphatic system, all white blood cells have nuclei, which distinguishes them from the other blood cells, the anucleated red blood cells and platelets. Types of white cells can be classified in standard ways. Two pairs of broadest categories classify them either by structure or by cell division lineage and these broadest categories can be further divided into the five main types, neutrophils, eosinophils, basophils, lymphocytes, and monocytes. These types are distinguished by their physical and functional characteristics, further subtypes can be classified, for example, among lymphocytes, there are B cells, T cells, and NK cells. The number of leukocytes in the blood is often an indicator of disease, the normal white cell count is usually between 4 × 109/L and 11 × 109/L. In the US this is expressed as 4,000 to 11,000 white blood cells per microliter of blood. They make up approximately 1% of the blood volume in a healthy adult. However, this 1% of the blood makes a difference to health. An increase in the number of leukocytes over the limits is called leukocytosis. It is normal when it is part of immune responses. It is occasionally abnormal, when it is neoplastic or autoimmune in origin, a decrease below the lower limit is called leukopenia. The name white blood cell derives from the appearance of a blood sample after centrifugation. White cells are found in the buff, a thin, typically white layer of nucleated cells between the red blood cells and the blood plasma. The scientific term leukocyte directly reflects its description and it is derived from the Greek roots leuk- meaning white and cyt- meaning cell. The buffy coat may sometimes be green if there are large amounts of neutrophils in the sample, all white blood cells are nucleated, which distinguishes them from the anucleated red blood cells and platelets. Types of leukocytes can be classified in standard ways, two pairs of broadest categories classify them either by structure or by cell lineage
5.
Latin
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Latin is a classical language belonging to the Italic branch of the Indo-European languages. The Latin alphabet is derived from the Etruscan and Greek alphabets, Latin was originally spoken in Latium, in the Italian Peninsula. Through the power of the Roman Republic, it became the dominant language, Vulgar Latin developed into the Romance languages, such as Italian, Portuguese, Spanish, French, and Romanian. Latin, Italian and French have contributed many words to the English language, Latin and Ancient Greek roots are used in theology, biology, and medicine. By the late Roman Republic, Old Latin had been standardised into Classical Latin, Vulgar Latin was the colloquial form spoken during the same time and attested in inscriptions and the works of comic playwrights like Plautus and Terence. Late Latin is the language from the 3rd century. Later, Early Modern Latin and Modern Latin evolved, Latin was used as the language of international communication, scholarship, and science until well into the 18th century, when it began to be supplanted by vernaculars. Ecclesiastical Latin remains the language of the Holy See and the Roman Rite of the Catholic Church. Today, many students, scholars and members of the Catholic clergy speak Latin fluently and it is taught in primary, secondary and postsecondary educational institutions around the world. The language has been passed down through various forms, some inscriptions have been published in an internationally agreed, monumental, multivolume series, the Corpus Inscriptionum Latinarum. Authors and publishers vary, but the format is about the same, volumes detailing inscriptions with a critical apparatus stating the provenance, the reading and interpretation of these inscriptions is the subject matter of the field of epigraphy. The works of several hundred ancient authors who wrote in Latin have survived in whole or in part and they are in part the subject matter of the field of classics. The Cat in the Hat, and a book of fairy tales, additional resources include phrasebooks and resources for rendering everyday phrases and concepts into Latin, such as Meissners Latin Phrasebook. The Latin influence in English has been significant at all stages of its insular development. From the 16th to the 18th centuries, English writers cobbled together huge numbers of new words from Latin and Greek words, dubbed inkhorn terms, as if they had spilled from a pot of ink. Many of these words were used once by the author and then forgotten, many of the most common polysyllabic English words are of Latin origin through the medium of Old French. Romance words make respectively 59%, 20% and 14% of English, German and those figures can rise dramatically when only non-compound and non-derived words are included. Accordingly, Romance words make roughly 35% of the vocabulary of Dutch, Roman engineering had the same effect on scientific terminology as a whole
6.
Terminologia Histologica
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The Terminologia Histologica is a controlled vocabulary for use in cytology and histology. In April 2011, Terminologia Histologica was published online by the Federative International Programme on Anatomical Terminologies and it was intended to replace Nomina Histologica. The Nomina Histologica was introduced in 1977, with the edition of Nomina Anatomica. It was developed by the Federative International Committee on Anatomical Terminology
7.
Vertebrate
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Vertebrates /ˈvɜːrtᵻbrᵻts/ comprise all species of animals within the subphylum Vertebrata /-ɑː/. Vertebrates represent the majority of the phylum Chordata, with currently about 66,000 species described. Vertebrates include the fish and the jawed vertebrates, which include the cartilaginous fish. A bony fish known as the lobe-finned fishes is included with tetrapods, which are further divided into amphibians, reptiles, mammals. Extant vertebrates range in size from the frog species Paedophryne amauensis, at as little as 7.7 mm, to the blue whale, vertebrates make up less than five percent of all described animal species, the rest are invertebrates, which lack vertebral columns. The vertebrates traditionally include the hagfish, which do not have proper vertebrae due to their loss in evolution, though their closest living relatives, hagfish do, however, possess a cranium. For this reason, the vertebrate subphylum is sometimes referred to as Craniata when discussing morphology, molecular analysis since 1992 has suggested that hagfish are most closely related to lampreys, and so also are vertebrates in a monophyletic sense. Others consider them a group of vertebrates in the common taxon of craniata. The word origin of vertebrate derives from the Latin word vertebratus, the Proto-Indo-European language origins are still unclear. Vertebrate is derived from the vertebra, which refers to any of the bones or segments of the spinal column. All vertebrates are built along the basic body plan, a stiff rod running through the length of the animal, with a hollow tube of nervous tissue above it. In all vertebrates, the mouth is found at, or right below, the remaining part of the body continuing after the anus forms a tail with vertebrae and spinal cord, but no gut. However, a few vertebrates have secondarily lost this anatomy, retaining the notochord into adulthood, such as the sturgeon, jawed vertebrates are typified by paired appendages, but this trait is not required in order for an animal to be a vertebrate. All basal vertebrates breathe with gills, the gills are carried right behind the head, bordering the posterior margins of a series of openings from the pharynx to the exterior. Each gill is supported by a cartilagenous or bony gill arch, the bony fish have three pairs of arches, cartilaginous fish have five to seven pairs, while the primitive jawless fish have seven. The vertebrate ancestor no doubt had more arches than this, as some of their relatives have more than 50 pairs of gills. In amphibians and some primitive fishes, the larvae bear external gills. These are reduced in adulthood, their function taken over by the gills proper in fishes, some amphibians retain the external larval gills in adulthood, the complex internal gill system as seen in fish apparently being irrevocably lost very early in the evolution of tetrapods
8.
Natural killer cell
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Natural killer cells or NK cells are a type of cytotoxic lymphocyte critical to the innate immune system. The role NK cells play is analogous to that of cytotoxic T cells in the adaptive immune response. NK cells provide rapid responses to viral-infected cells, acting at around 3 days after infection, typically, immune cells detect major histocompatibility complex presented on infected cell surfaces, triggering cytokine release, causing lysis or apoptosis. NK cells are unique, however, as they have the ability to recognize stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named natural killers because of the notion that they do not require activation to kill cells that are missing self markers of MHC class 1. This role is important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells. NK cells are defined as large granular lymphocytes and constitute the third kind of cells differentiated from the common lymphoid progenitor-generating B and T lymphocytes. NK cells are known to differentiate and mature in the marrow, lymph nodes, spleen, tonsils, and thymus. The NKp46 cell surface marker constitutes, at the moment, another NK cell marker of preference being expressed in humans, several strains of mice and in three common monkey species. The role of NK cells in both the innate and adaptive immune responses is becoming important in research using NK cell activity. NK cell receptors can also be differentiated based on function, NK Cells are not a subset of the T lymphocyte family. Natural cytotoxicity receptors directly induce apoptosis after binding to Fas ligand that directly indicate infection of a cell, the MHC-dependent receptors use an alternate pathway to induce apoptosis in infected cells. Natural killer cell activation is determined by the balance of inhibitory, for example, if the inhibitory receptor signaling is more prominent, then NK cell activity will be inhibited, similarly, if the activating signal is dominant, then NK cell activation will result. NCR, upon stimulation, mediate NK killing and release of IFNγ, cD94, NKG2, a C-type lectin family receptor, is conserved in both rodents and primates and identifies nonclassical MHC I molecules such as HLA-E. Though indirect, this is a way to survey the levels of classical HLA molecules, cD16 plays a role in antibody-dependent cell-mediated cytotoxicity, in particular, they bind IgG. Some KIRs are specific for certain HLA subtypes, most KIRs are inhibitory and dominant. Regular cells express MHC class 1, so are recognised by KIR receptors, ILT or LIR — are recently discovered members of the Ig receptor family. Ly49 have both activating and inhibitory isoforms and they are highly polymorphic on the population level, though they are structurally unrelated to KIRs, they are the functional homologues of KIRs in mice, including the expression pattern
9.
Innate immune system
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The cells of the innate system recognize and respond to pathogens in a generic way, but, unlike the adaptive immune system, the system does not provide long-lasting immunity to the host. Innate immune systems provide immediate defense against infection, and are found in all classes of plant, the innate immune system is an evolutionarily older defense strategy, and is the dominant immune system found in plants, fungi, insects, and primitive multicellular organisms. Anatomical barriers include physical, chemical and biological barriers, the epithelial surfaces form a physical barrier that is impermeable to most infectious agents, acting as the first line of defense against invading organisms. Desquamation of skin also helps remove bacteria and other infectious agents that have adhered to the epithelial surfaces. Lack of blood vessels and inability of the epidermis to retain moisture, in the gastrointestinal and respiratory tract, movement due to peristalsis or cilia, respectively, helps remove infectious agents. The gut flora can prevent the colonization of pathogenic bacteria by secreting toxic substances or by competing with pathogenic bacteria for nutrients or attachment to cell surfaces, the flushing action of tears and saliva helps prevent infection of the eyes and mouth. Inflammation is one of the first responses of the system to infection or irritation. The process of inflammation is initiated by cells already present in all tissues, mainly resident macrophages, dendritic cells, histiocytes, Kupffer cells. At the onset of an infection, burn, or other injuries, chemical factors produced during inflammation sensitize pain receptors, cause local vasodilation of the blood vessels, and attract phagocytes, especially neutrophils. Neutrophils then trigger other parts of the system by releasing factors that summon additional leukocytes and lymphocytes. Cytokines produced by macrophages and other cells of the immune system mediate the inflammatory response. These cytokines include TNF, HMGB1, and IL-1, the complement system is a biochemical cascade of the immune system that helps, or “complements”, the ability of antibodies to clear pathogens or mark them for destruction by other cells. The cascade is composed of plasma proteins, synthesized in the liver. Elements of the complement cascade can be found in many species including plants, birds, fish. All white blood cells are known as leukocytes, leukocytes are able to move freely and interact with and capture cellular debris, foreign particles, and invading microorganisms. Unlike many other cells in the body, most innate immune leukocytes cannot divide or reproduce on their own, mast cells are a type of innate immune cell that reside in connective tissue and in the mucous membranes. They are intimately associated with healing and defense against pathogens. When activated, mast cells rapidly release characteristic granules, rich in histamine and heparin, along with various hormonal mediators and chemokines, histamine dilates blood vessels, causing the characteristic signs of inflammation, and recruits neutrophils and macrophages
10.
T cell
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A T cell, or T lymphocyte, is a type of lymphocyte that plays a central role in cell-mediated immunity. T cells can be distinguished from other lymphocytes, such as B cells and natural killer cells and they are called T cells because they mature in the thymus from thymocytes. The several subsets of T cells each have a distinct function, the majority of human T cells rearrange their alpha and beta chains on the cell receptor and are termed alpha beta T cells and are part of the adaptive immune system. The category of effector T cell is a one that includes various T cell types that actively respond to a stimulus. This includes helper, killer, regulatory, and potentially other T cell types, T helper cells assist other white blood cells in immunologic processes, including maturation of B cells into plasma cells and memory B cells, and activation of cytotoxic T cells and macrophages. These cells are known as CD4+ T cells because they express the CD4 glycoprotein on their surfaces. Helper T cells become activated when they are presented with peptide antigens by MHC class II molecules, once activated, they divide rapidly and secrete small proteins called cytokines that regulate or assist in the active immune response. These cells can differentiate one of several subtypes, including TH1, TH2, TH3, TH17, TH9, or TFH. Signalling from the APC directs T cells into particular subtypes, cytotoxic T cells destroy virus-infected cells and tumor cells, and are also implicated in transplant rejection. These cells are known as CD8+ T cells since they express the CD8 glycoprotein at their surfaces. These cells recognize their targets by binding to antigen associated with MHC class I molecules, through IL-10, adenosine, and other molecules secreted by regulatory T cells, the CD8+ cells can be inactivated to an anergic state, which prevents autoimmune diseases. Appropriate co-stimulation must be present at the time of encounter for this process to occur. Historically, memory T cells were thought to belong to either the effector or central memory subtypes, subsequently, numerous new populations of memory T cells were discovered including tissue-resident memory T cells, stem memory TSCM cells, and virtual memory T cells. The single unifying theme for all memory T cell subtypes is that they are long-lived, by this mechanism they provide the immune system with memory against previously encountered pathogens. Memory T cells may be either CD4+ or CD8+ and usually express CD45RO, memory T cell subtypes, Central memory T cells express CD45RO, C-C chemokine receptor type 7, and L-selectin. Central memory T cells also have intermediate to high expression of CD44 and this memory subpopulation is commonly found in the lymph nodes and in the peripheral circulation. Effector memory T cells express CD45RO but lack expression of CCR7 and they also have intermediate to high expression of CD44. These memory T cells lack lymph node-homing receptors and are found in the peripheral circulation
11.
Adaptive immune system
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The adaptive immune system is one of the two main immunity strategies found in vertebrates. Adaptive immunity creates immunological memory after a response to a specific pathogen. This process of acquired immunity is the basis of vaccination, like the innate system, the adaptive system includes both humoral immunity components and cell-mediated immunity components. Unlike the innate system, the adaptive immune system is highly specific to a particular pathogen. Adaptive immunity can also provide long-lasting protection, for example, someone who recovers from measles is now protected against measles for their lifetime, in other cases it does not provide lifetime protection, for example, chickenpox. The adaptive system response destroys invading pathogens and any toxic molecules they produce, sometimes the adaptive system is unable to distinguish harmful from harmless foreign molecules, the effects of this may be hayfever, asthma or any other allergy. Antigens are any substances that elicit the immune response. The cells that carry out the immune response are white blood cells known as lymphocytes. Two main broad classes—antibody responses and cell mediated immune response—are also carried by two different lymphocytes, in antibody responses, B cells are activated to secrete antibodies, which are proteins also known as immunoglobulins. Antibodies travel through the bloodstream and bind to the foreign antigen causing it to inactivate, in acquired immunity, pathogen-specific receptors are acquired during the lifetime of the organism. The acquired response is called adaptive because it prepares the immune system for future challenges. The system is highly adaptable because of somatic hypermutation, and VJ recombination and this mechanism allows a small number of genes to generate a vast number of different antigen receptors, which are then uniquely expressed on each individual lymphocyte. A theoretical framework explaining the workings of the immune system is provided by immune network theory. This theory, which builds on established concepts of clonal selection, is being applied in the search for an HIV vaccine, the major functions of the adaptive immune system include, Recognition of specific non-self antigens in the presence of self, during the process of antigen presentation. Generation of responses that are tailored to eliminate specific pathogens or pathogen-infected cells. Development of immunological memory, in which pathogens are remembered through memory B cells, the cells of the adaptive immune system are T and B lymphocytes, lymphocytes are a subset of leukocyte. B cells and T cells are the types of lymphocytes. The human body has about 2 trillion lymphocytes, constituting 20–40% of white blood cells, the peripheral blood contains 2% of circulating lymphocytes, the rest move within the tissues and lymphatic system
12.
B cell
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B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the immune system by secreting antibodies. Additionally, B cells present antigen and secrete cytokines, in mammals, B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricius, B cells, unlike the other two classes of lymphocytes, T cells and natural killer cells, express B cell receptors on their cell membrane. BCRs allow the B cell to bind a specific antigen, against which it will initiate an antibody response, B cells develop from hematopoietic stem cells that originate from bone marrow. HSCs first differentiate into multipotent progenitor cells, then common lymphoid progenitor cells, B cells undergo two types of selection while developing in the bone marrow to ensure proper development. Positive selection occurs through antigen-independent signaling involving both the pre-BCR and the BCR, if these receptors do not bind to their ligand, B cells do not receive the proper signals and cease to develop. This negative selection process leads to a state of central tolerance, to complete development, immature B cells migrate from the bone marrow to the spleen as well as pass through two transitional stages, T1 and T2. Throughout their migration to the spleen and after spleen entry, they are considered T1 B cells, within the spleen, T1 B cells transition to T2 B cells. T2 B cells differentiate into either follicular B cells or marginal zone B cells depending on signals received through the BCR, once differentiated, they are now considered mature B cells, or naive B cells. While immature and during the T1 phase, B cells express BCRCR of class IgH, B cell activation occurs in the secondary lymphoid organs, such as the spleen and lymph nodes. After B cells mature in the marrow, they migrate through the blood to SLOs. At the SLO, B cell activation begins when the B cell binds to an antigen via its BCR, antigen is presented to lymphocytes by APCs such as macrophages or dendritic cells, and include proteins, glycoproteins, polysaccharides, whole virus particles, and whole bacterial cells. Of the three B cell subsets, FO B cells preferentially undergo T cell-dependent activation while MZ B cells, B cell activation is enhanced through the activity of CD21, a surface receptor in complex with surface proteins CD19 and CD81. Antigens that activate B cells with the help of T-cell are known as T cell-dependent antigens and they are named as such because they are unable to induce a humoral response in organisms that lack T cells. B cell response to these antigens takes multiple days, though antibodies generated have an affinity and are more functionally versatile than those generated from T cell-independent activation. T helper cells, typically follicular T helper cells, that were activated with the same antigen recognize, following TCR-MHC-II-peptide binding, T cells express the surface protein CD40L as well as cytokines such as IL-4 and IL-21. T cell-derived cytokines bound by B cell cytokine receptors also promote B cell proliferation, immunoglobulin class switching, after B cells receive these signals, they are considered activated
13.
Humoral immunity
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Humoral immunity is so named because it involves substances found in the humors, or body fluids. Its aspects involving antibodies are often called antibody-mediated immunity, the study of the molecular and cellular components that form the immune system, including their function and interaction, is the central science of immunology. The immune system is divided into a more primitive innate immune system, the concept of humoral immunity developed based on analysis of antibacterial activity of the serum components. Hans Buchner is credited with the development of the humoral theory, in 1890 he described alexins, or “protective substances”, which exist in the blood serum and other bodily fluid and are capable of killing microorganisms. Following the 1888 discovery of the bacteria that cause diphtheria and tetanus, Emil von Behring and they discovered that cell-free filtrates were sufficient to cause disease. In 1897, Paul Ehrlich showed that antibodies form against the plant toxins ricin and abrin, Ehrlich, with his friend Emil von Behring, went on to develop the diphtheria antitoxin, which became the first major success of modern immunotherapy. The presence and specificity of compatibility antibodies became the tool for standardizing the state of immunity. The complement system is a cascade of the innate immune system that helps clear pathogens from an organism. It is derived from many small blood plasma proteins that together to disrupt the target cells plasma membrane leading to cytolysis of the cell. The complement system consists of more than 35 soluble and cell-bound proteins,12 of which are involved in the complement pathways. The complement system is involved in the activities of both innate immunity and acquired immunity, activation of this system leads to cytolysis, chemotaxis, opsonization, immune clearance, and inflammation, as well as the marking of pathogens for phagocytosis. The proteins account for 5% of the globulin fraction. Most of these proteins circulate as zymogens, which are inactive until proteolytic cleavage, three biochemical pathways activate the complement system, the classical complement pathway, the alternate complement pathway, and the mannose-binding lectin pathway. Antibodies, in particular the IgG1 class, can also fix complement, the principal function of B cells is to make antibodies against soluble antigens. B cell recognition of antigen is not the only element necessary for B cell activation, naïve B cells can be activated in a T-cell dependent or independent manner, but two signals are always required to initiate activation. B cell activation depends on one of three mechanisms, Type 1 T cell-independent activation, Type 2 T cell-independent activation, and T cell-dependent activation, during T cell-dependent activation, an antigen presenting cell presents a processed antigen to a T helper cell, priming it. When a B cell processes and presents the antigen to the primed Th cell. Immunoglobulins are glycoproteins in the superfamily that function as antibodies
14.
Antibody
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An antibody, also known as an immunoglobulin, is a large, Y-shaped protein produced mainly by plasma cells that is used by the immune system to neutralize pathogens such as bacteria and viruses. The antibody recognizes a molecule of the harmful agent, called an antigen. Each tip of the Y of an antibody contains a paratope that is specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or a cell for attack by other parts of the immune system. Depending on the antigen, the binding may impede the process causing the disease or may activate macrophages to destroy the foreign substance. The ability of an antibody to communicate with the components of the immune system is mediated via its Fc region. The production of antibodies is the function of the humoral immune system. Antibodies are secreted by B cells of the immune system. In most cases, interaction of the B cell with a T helper cell is necessary to produce full activation of the B cell and, therefore, soluble antibodies are released into the blood and tissue fluids, as well as many secretions to continue to survey for invading microorganisms. Antibodies are glycoproteins belonging to the immunoglobulin superfamily and they constitute most of the gamma globulin fraction of the blood proteins. They are typically made of basic structural units—each with two heavy chains and two small light chains. There are several different types of heavy chains that define the five different types of crystallisable fragments that may be attached to the antigen-binding fragments. The five different types of Fc regions allow antibodies to be grouped into five isotypes, each Fc region of a particular antibody isotype is able to bind to its specific Fc Receptor, thus allowing the antigen-antibody complex to mediate different roles depending on which FcR it binds. The ability of an antibody to bind to its corresponding FcR is further modulated by the structure of the present at conserved sites within its Fc region. The ability of antibodies to bind to FcRs helps to direct the immune response for each different type of foreign object they encounter. For example, IgE is responsible for an allergic response consisting of mast cell degranulation, igEs Fab paratope binds to allergic antigen, for example house dust mite particles, while its Fc region binds to Fc receptor ε. The allergen-IgE-FcRε interaction mediates allergic signal transduction to induce conditions such as asthma and this region is known as the hypervariable region. Each of these variants can bind to a different antigen and this enormous diversity of antibody paratopes on the antigen-binding fragments allows the immune system to recognize an equally wide variety of antigens
15.
Lymph
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Lymph is the fluid that circulates throughout the lymphatic system. The lymph is formed when the fluid is collected through lymph capillaries. Since the lymph is derived from the fluid, its composition continually changes as the blood. It is generally similar to blood plasma except that it doesnt contain red blood cells, lymph returns proteins and excess interstitial fluid to the bloodstream. Lymph may pick up bacteria and bring them to lymph nodes, metastatic cancer cells can also be transported via lymph. Lymph also transports fats from the system to the blood via chylomicrons. The word lymph is derived from the name of the ancient Roman deity of fresh water, lymph has a composition comparable to that of blood plasma, but it may differ slightly. In particular, the lymph that leaves a lymph node is richer in lymphocytes, likewise, the lymph formed in the human digestive system called chyle is rich in triglycerides, and looks milky white because of its lipid content. As the blood and the surrounding cells continually add and remove substances from the interstitial fluid, thus, lymph when formed is a watery clear liquid with the same composition as the interstitial fluid. However, as it flows through the nodes it comes in contact with blood. Tubular vessels transport lymph back to the blood, ultimately replacing the volume lost during the formation of the interstitial fluid and these channels are the lymphatic channels, or simply lymphatics. Unlike the cardiovascular system, the system is not closed and has no central pump. Lymph transport, therefore, is slow and sporadic, despite low pressure, lymph movement occurs due to peristalsis, valves, and compression during contraction of adjacent skeletal muscle and arterial pulsation. Lymph that enters the lymph vessels from the interstitial spaces usually does not flow backwards along the vessels because of the presence of valves. If excessive hydrostatic pressure develops within the vessels, though, some fluid can leak back into the interstitial spaces. Flow of the lymph in the duct in an average resting person usually approximates 100ml per hour. Accompanied by another ~25ml per hour in other vessels, total lymph flow in the body is about 4 to 5 liters per day. Which can be elevated several folds in case of exercising, thus it can be estimated that without lymphatic flow, an average resting person would die within 24 hours
16.
Red blood cell
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RBCs take up oxygen in the lungs, or gills of fish, and release it into tissues while squeezing through the bodys capillaries. The cytoplasm of erythrocytes is rich in hemoglobin, a biomolecule that can bind oxygen and is responsible for the red color of the cells. In humans, mature red cells are flexible and oval biconcave disks. They lack a nucleus and most organelles, in order to accommodate maximum space for hemoglobin, they can be viewed as sacks of hemoglobin. Approximately 2.4 million new erythrocytes are produced per second in human adults, the cells develop in the bone marrow and circulate for about 100–120 days in the body before their components are recycled by macrophages. Each circulation takes about 60 seconds, approximately a quarter of the cells in the human body are red blood cells. Nearly half of the volume is red blood cells. Red blood cells are known as RBCs, red cells, red blood corpuscles, haematids. Packed red blood cells are red blood cells that have donated, processed. Almost all vertebrates, including all mammals and humans, have red blood cells, red blood cells are cells present in blood in order to transport oxygen. The only known vertebrates without red blood cells are the crocodile icefish, they live in very cold water. While they no longer use hemoglobin, remnants of hemoglobin genes can be found in their genome, oxygen can easily diffuse through the red blood cells cell membrane. Myoglobin, a related to hemoglobin, acts to store oxygen in muscle cells. The color of red cells is due to the heme group of hemoglobin. However, blood can appear bluish when seen through the vessel wall, pulse oximetry takes advantage of the hemoglobin color change to directly measure the arterial blood oxygen saturation using colorimetric techniques. Hemoglobin also has a high affinity for carbon monoxide, forming carboxyhemoglobin which is a very bright red in color. Flushed, confused patients with a reading of 100% on pulse oximetry are sometimes found to be suffering from carbon monoxide poisoning. The red blood cells of mammals are typically shaped as disks, flattened and depressed in the center, with a dumbbell-shaped cross section
17.
Optical microscope
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The optical microscope, often referred to as light microscope, is a type of microscope which uses visible light and a system of lenses to magnify images of small samples. Optical microscopes are the oldest design of microscope and were invented in their present compound form in the 17th century. Basic optical microscopes can be simple, although there are many complex designs which aim to improve resolution. The image from a microscope can be captured by normal light-sensitive cameras to generate a micrograph. Originally images were captured by photographic film but modern developments in CMOS, purely digital microscopes are now available which use a CCD camera to examine a sample, showing the resulting image directly on a computer screen without the need for eyepieces. Alternatives to optical microscopy which do not use visible light include scanning electron microscopy, there are two basic types of optical microscopes, simple microscopes and compound microscopes. A simple microscope is one which uses a lens for magnification. A compound microscope uses several lenses to enhance the magnification of an object, the vast majority of modern research microscopes are compound microscopes while some cheaper commercial digital microscopes are simple single lens microscopes. Compound microscopes can be divided into a variety of other types of microscopes which differ in their optical configurations, cost. A simple microscope uses a lens or set of lenses to enlarge an object through angular magnification alone, the use of a single convex lens or groups of lenses are still found in simple magnification devices such as the magnifying glass, loupes, and eyepieces for telescopes and microscopes. A compound microscope uses a close to the object being viewed to collect light which focuses a real image of the object inside the microscope. That image is magnified by a second lens or group of lenses that gives the viewer an enlarged inverted virtual image of the object. The use of a compound objective/eyepiece combination allows for higher magnification. Common compound microscopes often feature exchangeable objective lenses, allowing the user to quickly adjust the magnification, a compound microscope also enables more advanced illumination setups, such as phase contrast. There are many variants of the optical microscope design for specialized purposes. Comparison microscope, which has two light paths allowing direct comparison of two samples via one image in each eye. Inverted microscope, for studying samples from below, useful for cell cultures in liquid, student microscope, designed for low cost, durability, and ease of use. Polarizing microscope, similar to the petrographic microscope, phase contrast microscope, which applies the phase contrast illumination method
18.
Antigen presentation
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Antigen presentation describes a vital immune process which is essential for T cell immune response triggering. Cellular membranes separate these two cellular environments - intracellular and extracellular, cytotoxic T cells express CD8 coreceptor are a population of T cells that are specialised for inducing programmed cell death of other cells. Cytotoxic T cells regularly patrol all body cells to maintain the organismal homeostasis, all nucleated cells in the body display class I major histocompatibility complex. Antigens generated endogenously within these cells are bound to MHC-I molecules and this antigen presentation pathway enables the immune system to detect transformed or infected cells displaying peptides from modified-self or foreign proteins. In the presentation process, these proteins are mainly degraded into small peptides by proteases in the proteasome. There are several ER chaperones involved in MHC-I assembly, such as calnexin, clareticulin and tapasin, peptides are loaded to MHC-I peptide binding groove between two alpha helices at the bottom of the α1 and α2 domains of the MHC class I molecule. After releasing from tapasin, peptide-MHC-I complexes exit the ER and are transported to the surface by exocytic vesicles. Naïve anti-viral T cells cannot directly eliminate transformed or infected cells and they have to be activated by the pMHC-I complexes of antigen-presenting cells. Here, antigen can be presented directly or indirectly from virus-infected and non-infected cells, cross-presentation is a special case in which MHC-I molecules are able to present extracellular antigens, usually displayed only by MHC-II molecules. This ability appears in several APCs, mainly plasmacytoid dendritic cells in tissues that stimulate CD8+ T cells directly and this process is essential when APCs are not directly infected, triggering local antiviral and anti-tumor immune responses immediately without trafficking the APCs in the local lymph nodes. APCs usually internalise exogenous antigens by endocytosis, but also by pinocytosis, macroautophagy, in the first case, after internalisation, the antigens are enclosed in vesicles called endosomes. This process is favored by gradual reduction of the pH, the main proteases in endosomes are cathepsins and the result is the degradation of the antigens into oligopeptides. MHC-II molecules are transported from the ER to the MHC class II loading compartment together with the protein Invariant chain, a non classical MHC-II molecule catalyses the exchange of part of the CD74 with the peptide antigen. Peptide-MHC-II complexes are transported to the membrane and the processed antigen is presented to the helper T cells in the lymph nodes. As well as in CD8+ cytotoxic T cells, APCs need pMHC-II, alternative pathway of endogenous antigen processing and presentation over MHC-II molecules exists in medulary thymic epithelial cells via the process of autophagy. It is important for the process of central tolerance of T cells in particular the selection of autoreactive clones. Random gene expression of the genome is achieved via the action of AIRE. Large complexes of antigen are presented in lymph nodes to B cells by follicular dendritic cells in the form of immune complexes
19.
Bacteria
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Bacteria constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a number of shapes, ranging from spheres to rods, Bacteria were among the first life forms to appear on Earth, and are present in most of its habitats. Bacteria inhabit soil, water, acidic hot springs, radioactive waste, Bacteria also live in symbiotic and parasitic relationships with plants and animals. Most bacteria have not been characterised, and only half of the bacterial phyla have species that can be grown in the laboratory. The study of bacteria is known as bacteriology, a branch of microbiology, There are typically 40 million bacterial cells in a gram of soil and a million bacterial cells in a millilitre of fresh water. There are approximately 5×1030 bacteria on Earth, forming a biomass which exceeds that of all plants, Bacteria are vital in many stages of the nutrient cycle by recycling nutrients such as the fixation of nitrogen from the atmosphere. The nutrient cycle includes the decomposition of bodies and bacteria are responsible for the putrefaction stage in this process. In March 2013, data reported by researchers in October 2012, was published and it was suggested that bacteria thrive in the Mariana Trench, which with a depth of up to 11 kilometres is the deepest known part of the oceans. Other researchers reported related studies that microbes thrive inside rocks up to 580 metres below the sea floor under 2.6 kilometres of ocean off the coast of the northwestern United States. According to one of the researchers, You can find microbes everywhere—theyre extremely adaptable to conditions, the vast majority of the bacteria in the body are rendered harmless by the protective effects of the immune system, though many are beneficial particularly in the gut flora. However several species of bacteria are pathogenic and cause diseases, including cholera, syphilis, anthrax, leprosy. The most common fatal diseases are respiratory infections, with tuberculosis alone killing about 2 million people per year. In developed countries, antibiotics are used to treat infections and are also used in farming, making antibiotic resistance a growing problem. Once regarded as constituting the class Schizomycetes, bacteria are now classified as prokaryotes. Unlike cells of animals and other eukaryotes, bacterial cells do not contain a nucleus and these evolutionary domains are called Bacteria and Archaea. The ancestors of modern bacteria were unicellular microorganisms that were the first forms of life to appear on Earth, for about 3 billion years, most organisms were microscopic, and bacteria and archaea were the dominant forms of life. In 2008, fossils of macroorganisms were discovered and named as the Francevillian biota, however, gene sequences can be used to reconstruct the bacterial phylogeny, and these studies indicate that bacteria diverged first from the archaeal/eukaryotic lineage. Bacteria were also involved in the second great evolutionary divergence, that of the archaea, here, eukaryotes resulted from the entering of ancient bacteria into endosymbiotic associations with the ancestors of eukaryotic cells, which were themselves possibly related to the Archaea
20.
T helper cell
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The T helper cells are a type of T cell that play an important role in the immune system, particularly in the adaptive immune system. They help the activity of immune cells by releasing T cell cytokines. These cells help suppress or regulate immune responses and they are essential in B cell antibody class switching, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages. Mature Th cells express the surface protein CD4 and are referred to as CD4+ T cells, such CD4+ T cells are generally treated as having a pre-defined role as helper T cells within the immune system. For example, when a cell expresses an antigen on MHC class II. CD154, also called CD40 ligand or CD40L, is a surface protein that mediates T cell helper function in a contact-dependent process and is a member of the TNF superfamily of molecules. It binds to CD40 on antigen-presenting cells, which leads to many effects depending on the cell type. CD154 acts as a molecule and is particularly important on a subset of T cells called T follicular helper cells. On TFH cells, CD154 promotes B cell maturation and function by engaging CD40 on the B cell surface, a defect in this gene results in an inability to undergo immunoglobulin class switching and is associated with hyper IgM syndrome. Absence of CD154 also stops the formation of germinal centers and therefore prohibiting antibody affinity maturation, the importance of helper T cells can be seen from HIV, a virus that primarily infects CD4+ T cells. In the advanced stages of HIV infection, loss of functional CD4+ T cells leads to the stage of infection known as the acquired immunodeficiency syndrome. When the HIV virus is detected early in blood or other bodily fluids, therapy can also better manage the course of AIDS if and when it occurs. There are other rare disorders such as lymphocytopenia which result in the absence or dysfunction of CD4+ T cells and these disorders produce similar symptoms, many of which are fatal. Following T cell development, matured, naïve T cells leave the thymus and begin to spread throughout the body, like all T cells, they express the T cell receptor-CD3 complex. The T cell receptor consists of constant and variable regions. The variable region determines what antigen the T cell can respond to, CD4+ T cells have TCRs with an affinity for Class II MHC, and CD4 is involved in determining MHC affinity during maturation in the thymus. Class II MHC proteins are only found on the surface of specialised antigen-presenting cells. Specialised antigen presenting cells are dendritic cells, macrophages and B cells
21.
Cytotoxic T cell
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A cytotoxic T cell is a T lymphocyte that kills cancer cells, cells that are infected, or cells that are damaged in other ways. Most cytotoxic T cells express T-cell receptors that can recognize a specific antigen, an antigen is a molecule capable of stimulating an immune response, and is often produced by cancer cells or viruses. Antigens inside a cell are bound to class I MHC molecules, and brought to the surface of the cell by the class I MHC molecule, where they can be recognized by the T cell. If the TCR is specific for that antigen, it binds to the complex of the class I MHC molecule and the antigen, and the T cell destroys the cell. In order for the TCR to bind to the class I MHC molecule, the former must be accompanied by a glycoprotein called CD8, therefore, these T cells are called CD8+ T cells. The affinity between CD8 and the MHC molecule keeps the TC cell and the target cell bound together during antigen-specific activation. CD8+ T cells are recognized as TC cells once they become activated and are classified as having a pre-defined cytotoxic role within the immune system. However, CD8+ T cells also have the ability to make some cytokines, the immune system must recognize millions of potential antigens. There are fewer than 30,000 genes in the human body, instead, the DNA in millions of white blood cells in the bone marrow is shuffled to create cells with unique receptors, each of which can bind to a different antigen. Some receptors bind to tissues in the body itself, so to prevent the body from attacking itself. TCRs have two parts, usually an alpha and a beta chain, if that rearrangement is successful, the cells then rearrange their alpha-chain TCR DNA to create a functional alpha-beta TCR complex. The vast majority of T cells express alpha-beta TCRs, but some T cells in epithelial tissues express gamma-delta TCRs, T cells with functionally stable TCRs express both the CD4 and CD8 co-receptors and are therefore termed double-positive T cells. Only those T cells that bind to the MHC-self-antigen complexes weakly are positively selected and it is the CD8+ T-cells that will mature and go on to become cytotoxic T cells following their activation with a class I-restricted antigen. With an exception of some types, such as non-nucleated cells. When these cells are infected with a virus, the cells degrade foreign proteins via antigen processing and these result in peptide fragments, some of which are presented by MHC Class I to the T cell antigen receptor on CD8+ T cells. For instance, consider the two signal model for TC cell activation, a simple activation of naive CD8+ T cells requires the interaction with professional antigen-presenting cells, mainly with matured dendritic cells. To generate longlasting memory T cells and to allow repetitive stimulation of cytotoxic T cells, during this process, the CD4+ helper T cells license the dendritic cells to give a potent activating signal to the naive CD8+ T cells. While in most cases activation is dependent on TCR recognition of antigen, for example, cytotoxic T cells have been shown to become activated when targeted by other CD8 T cells leading to tolerization of the latter
22.
Enzyme
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Enzymes /ˈɛnzaɪmz/ are macromolecular biological catalysts. Enzymes accelerate, or catalyze, chemical reactions, the molecules at the beginning of the process upon which enzymes may act are called substrates and the enzyme converts these into different molecules, called products. Almost all metabolic processes in the cell need enzymes in order to occur at rates fast enough to sustain life, the set of enzymes made in a cell determines which metabolic pathways occur in that cell. The study of enzymes is called enzymology, enzymes are known to catalyze more than 5,000 biochemical reaction types. Most enzymes are proteins, although a few are catalytic RNA molecules, enzymes specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the rate of a reaction by lowering its activation energy, some enzymes can make their conversion of substrate to product occur many millions of times faster. An extreme example is orotidine 5-phosphate decarboxylase, which allows a reaction that would take millions of years to occur in milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, enzymes differ from most other catalysts by being much more specific. Enzyme activity can be affected by other molecules, inhibitors are molecules that decrease enzyme activity, many drugs and poisons are enzyme inhibitors. An enzymes activity decreases markedly outside its optimal temperature and pH, some enzymes are used commercially, for example, in the synthesis of antibiotics. French chemist Anselme Payen was the first to discover an enzyme, diastase and he wrote that alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells. In 1877, German physiologist Wilhelm Kühne first used the term enzyme, the word enzyme was used later to refer to nonliving substances such as pepsin, and the word ferment was used to refer to chemical activity produced by living organisms. Eduard Buchner submitted his first paper on the study of yeast extracts in 1897, in a series of experiments at the University of Berlin, he found that sugar was fermented by yeast extracts even when there were no living yeast cells in the mixture. He named the enzyme that brought about the fermentation of sucrose zymase, in 1907, he received the Nobel Prize in Chemistry for his discovery of cell-free fermentation. Following Buchners example, enzymes are usually named according to the reaction they carry out, the biochemical identity of enzymes was still unknown in the early 1900s. Sumner showed that the enzyme urease was a protein and crystallized it. These three scientists were awarded the 1946 Nobel Prize in Chemistry, the discovery that enzymes could be crystallized eventually allowed their structures to be solved by x-ray crystallography. This high-resolution structure of lysozyme marked the beginning of the field of structural biology, an enzymes name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase
23.
Immunity (medical)
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Immunity is the capability of multicellular organisms to resist harmful microorganisms from entering it. Immunity involves both specific and nonspecific components, the nonspecific components act as barriers or eliminators of a wide range of pathogens irrespective of their antigenic make-up. Other components of the immune system adapt themselves to each new disease encountered and are able to generate pathogen-specific immunity, an immune system may contain innate and adaptive components. The innate system in mammalians for example is composed of bone marrow cells that are programmed to recognise foreign substances. The adaptive system is composed of more advanced lymphatic cells that are programmed to recognise self substances, the reaction to foreign substances is etymologically described as inflammation, meaning to set on fire. The non-reaction to self substances is described as immunity, meaning to exempt or as immunotolerance, disease can arise when what is foreign cannot be eliminated or what is self is not spared. Innate immunity, also called native immunity, exists by virtue of an organisms constitution and it is divided into two types, Non-Specific innate immunity, a degree of resistance to all infections in general. Specific innate immunity, a resistance to a kind of microorganism only. As a result some races, specific individuals or breeds in agriculture do not suffer from certain infectious diseases, passive immunity is acquired through transfer of antibodies or activated T-cells from an immune host, it is short lived—usually lasting only a few months. The diagram below summarizes these divisions of immunity, humoral immunity is called active when the organism generates its own antibodies, and passive when antibodies are transferred between individuals or species. Similarly, cell mediated immunity is active when the organisms’ own T-cells are stimulated, the concept of immunity has intrigued mankind for thousands of years. Between the time of Hippocrates and the 19th century, when the foundations of the methods were laid. If someone were exposed to the miasma in a swamp, in evening air, or breathing air in a sickroom or hospital ward, the modern word immunity derives from the Latin immunis, meaning exemption from military service, tax payments or other public services. For no one was attacked a second time, or not with a fatal result. The term immunes, is found in the epic poem Pharsalia written around 60 B. C. by the poet Marcus Annaeus Lucanus to describe a North African tribes resistance to snake venom. In the treatise, Al Razi describes the presentation of smallpox. The first scientist who developed full theory of immunity was Ilya Mechnikov after he revealed phagocytosis in 1882, the birth of active immunotherapy may have begun with Mithridates VI of Pontus. To induce active immunity for snake venom, he recommended using a similar to modern toxoid serum therapy
24.
Major histocompatibility complex
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The main function of MHC molecules is to bind to antigens derived from pathogens and display them on the cell surface for recognition by the appropriate T-cells. MHC molecules mediate interactions of leukocytes, also called white blood cells, the MHC determines compatibility of donors for organ transplant, as well as ones susceptibility to an autoimmune disease via crossreacting immunization. The human MHC is also called the HLA complex, the mouse MHC is called the H-2 complex or H-2. In a cell, protein molecules of the hosts own phenotype or of other entities are continually synthesized and degraded. Each MHC molecule on the surface displays a molecular fraction of a protein. The presented antigen can be either self or non-self, thus preventing an immune system targeting its own cells. In its entirety, the MHC population is like a meter indicating the balance of proteins within the cell, the MHC gene family is divided into three subgroups, class I, class II, and class III. Class I MHC molecules have β2 subunits so can only be recognised by CD8 co-receptors, class II MHC molecules have β1 and β2 subunits and can be recognised by CD4 co-receptors. In this way MHC molecules chaperone which type of lymphocytes may bind to the antigen with high affinity. Major histocompatibility complex and sexual selection has been observed in male mice making mate choices of females with different MHCs, also, at least for MHC I presentation, there has been evidence of antigenic peptide splicing which can combine peptides from different proteins, vastly increasing antigen diversity. The first descriptions of the MHC were made by British immunologist Peter Gorer in 1936, MHC genes were first identified in inbred mice strains. Clarence Little transplanted tumors across differing strains and found rejection of transplanted tumors according to strains of host versus donor, for this work, Snell was awarded the 1980 Nobel Prize in Physiology or Medicine, together with Baruj Benacerraf and Jean Dausset and Duncan Rhodes. Of the three MHC classes identified, attention commonly focuses on classes I and II, by interacting with CD4 molecules on surfaces of helper T cells, MHC class II mediates establishment of specific immunity. By interacting with CD8 molecules on surfaces of cytotoxic T cells, MHC class I mediates destruction of infected or malignant host cells, MHC is the tissue-antigen that allows the immune system to bind to, recognize, and tolerate itself. MHC is also the chaperone for intracellular peptides that are complexed with MHCs, essentially, the MHC-peptide complex is a complex of autoantigen/alloantigen. Upon binding, T cells should in principle tolerate the auto-antigen, disease states occur when this principle is disrupted. Tissue allorecognition, MHC molecules in complex with peptide epitopes are essentially ligands for TCR, T cells become activated by binding to the peptide-binding grooves of any MHC molecule that T cells were not trained to recognize during thymus positive selection. As a lineage of leukocytes, lymphocytes reside in peripheral tissues, including lymphoid follicles and lymph nodes, and include B cells, T cells
25.
MHC class I
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MHC class I molecules are one of two primary classes of major histocompatibility complex molecules and are found on the cell surface of all nucleated cells in the bodies of jawed vertebrates. They also occur on platelets, but not on red blood cells, because MHC class I molecules present peptides derived from cytosolic proteins, the pathway of MHC class I presentation is often called cytosolic or endogenous pathway. In humans, the HLAs corresponding to MHC class I are HLA-A, HLA-B, Class I MHC molecules bind peptides generated mainly from degradation of cytosolic proteins by the proteasome. The MHC I, peptide complex is then inserted via endoplasmic reticulum into the plasma membrane of the cell. The epitope peptide is bound on extracellular parts of the class I MHC molecule, thus, the function of the class I MHC is to display intracellular proteins to cytotoxic T cells. However, class I MHC can also present peptides generated from exogenous proteins, a normal cell will display peptides from normal cellular protein turnover on its class I MHC, and CTLs will not be activated in response to them due to central and peripheral tolerance mechanisms. When a cell expresses foreign proteins, such as viral infection. Consequently, CTLs specific for the MHC, peptide complex will recognize, alternatively, class I MHC itself can serve as an inhibitory ligand for natural killer cells. Reduction in the levels of surface class I MHC, a mechanism employed by some viruses. Paired-immunoglobulin-like receptor B, an MHCI-binding receptor, is involved in the regulation of visual plasticity, PirB is expressed in the central nervous system and diminishes ocular dominance plasticity in the developmental critical period and adulthood. When the function of PirB was abolished in mutant mice, ocular dominance plasticity became more pronounced at all ages, PirB loss of function mutant mice also exhibited enhanced plasticity after monocular deprivation during the critical period. These results suggest PirB may be involved in modulation of synaptic plasticity in the visual cortex, MHC class I molecules are heterodimers that consist of two polypeptide chains, α and β2-microglobulin. The two chains are linked noncovalently via interaction of b2m and the α3 domain, only the α chain is polymorphic and encoded by a HLA gene, while the b2m subunit is not polymorphic and encoded by the Beta-2 microglobulin gene. The α3 domain is plasma membrane-spanning and interacts with the CD8 co-receptor of T-cells, the α1 and α2 domains fold to make up a groove for peptides to bind. MHC class I molecules bind peptides that are 8-10 amino acid in length, the peptides are generated mainly in the cytosol by the proteasome. The proteasome is a macromolecule that consists of 28 subunits, of which half affect proteolytic activity, the proteasome degrades intracellular proteins into small peptides that are then released into the cytosol. The peptides have to be translocated from the cytosol into the endoplasmic reticulum to meet the MHC class I molecule and they have membrane proximal Ig fold. The peptide translocation from the cytosol into the lumen of the ER is accomplished by the associated with antigen processing
26.
Interferon
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Interferons are a group of signaling proteins made and released by host cells in response to the presence of several pathogens, such as viruses, bacteria, parasites, and also tumor cells. In a typical scenario, a cell will release interferons causing nearby cells to heighten their anti-viral defenses. IFNs belong to the class of proteins known as cytokines, molecules used for communication between cells to trigger the protective defenses of the immune system that help eradicate pathogens. Interferons are named for their ability to interfere with viral replication by protecting cells from virus infections, certain symptoms of infections, such as fever, muscle pain and flu-like symptoms, are also caused by the production of IFNs and other cytokines. More than twenty distinct IFN genes and proteins have been identified in animals and they are typically divided among three classes, Type I IFN, Type II IFN, and Type III IFN. IFNs belonging to all three classes are important for fighting infections and for the regulation of the immune system. Based on the type of receptor through which they signal, human interferons have been classified into three major types, Interferon type I, All type I IFNs bind to a specific cell surface receptor complex known as the IFN-α/β receptor that consists of IFNAR1 and IFNAR2 chains. The type I interferons present in humans are IFN-α, IFN-β, IFN-ε, IFN-κ, in general, type I interferons are produced when the body recognizes a virus has invaded it. They are produced by fibroblasts and monocytes, however, the production of type I IFN-α is prohibited by another cytokine known as Interleukin-10. Once released, type I interferons will activate molecules which prevent the virus from producing and replicating its RNA and DNA, overall, IFN-α can be used to treat hepatitis B and C infections, while IFN-β can be used to treat multiple sclerosis. Interferon type II, This is also known as immune interferon and is activated by Interleukin-12, furthermore, type II interferons are released by T helper cells, type 1 specifically. However, they block the proliferation of T helper cells type two, the previous results in an inhibition of Th2 immune response and a further induction of Th1 immune response, which leads to the development of debilitating diseases such as multiple sclerosis. IFN type II binds to IFNGR, which consists of IFNGR1, Interferon type III, Signal through a receptor complex consisting of IL10R2 and IFNLR1. Although discovered more recently than type I and type II IFNs, in general, type I and II interferons are responsible for regulating and activating the immune response. All interferons share several common effects, they are antiviral agents, administration of Type I IFN has been shown experimentally to inhibit tumor growth in animals, but the beneficial action in human tumors has not been widely documented. A virus-infected cell releases viral particles that can infect nearby cells, however, the infected cell can prepare neighboring cells against a potential infection by the virus by releasing interferons. In response to interferon, cells produce large amounts of a known as protein kinase R. Another cellular enzyme, RNAse L—also induced by interferon action—destroys RNA within the cells to reduce protein synthesis of both viral and host genes
27.
Haematopoiesis
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Haematopoiesis is the formation of blood cellular components. All cellular blood components are derived from stem cells. In a healthy person, approximately 1011–1012 new blood cells are produced daily in order to maintain steady state levels in the peripheral circulation. Haematopoietic stem cells reside in the medulla of the bone and have the ability to give rise to all of the different mature blood cell types and tissues. HSCs are self-renewing cells, when they proliferate, at least some of their daughter cells remain as HSCs, so the pool of stem cells is not depleted. This phenomenon is called asymmetric division. The other daughters of HSCs can follow any of the other pathways that lead to the production of one or more specific types of blood cell. The pool of progenitors is heterogeneous and can be divided into two groups, long-term self-renewing HSC and only transiently self-renewing HSC, also called short-terms and this is one of the main vital processes in the body. All blood cells are divided into three lineages, erythroid cells are the oxygen carrying red blood cells. Both reticulocytes and erythrocytes are functional and are released into the blood, in fact, a reticulocyte count estimates the rate of erythropoiesis. Lymphocytes are the cornerstone of the immune system. They are derived from common lymphoid progenitors, the lymphoid lineage is primarily composed of T-cells and B-cells. In developing embryos, blood formation occurs in aggregates of cells in the yolk sac. As development progresses, blood formation occurs in the spleen, liver, when bone marrow develops, it eventually assumes the task of forming most of the blood cells for the entire organism. However, maturation, activation, and some proliferation of lymphoid cells occurs in the spleen, thymus, in children, haematopoiesis occurs in the marrow of the long bones such as the femur and tibia. In adults, it mainly in the pelvis, cranium, vertebrae. In some cases, the liver, thymus, and spleen may resume their haematopoietic function and it may cause these organs to increase in size substantially. During fetal development, since bones and thus the bone marrow develop later, therefore, the liver is enlarged during development. In some vertebrates, haematopoiesis can occur wherever there is a loose stroma of connective tissue and slow blood supply, such as the gut, spleen or kidney
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Stem cell
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Stem cells are undifferentiated biological cells that can differentiate into specialized cells and can divide to produce more stem cells. They are found in multicellular organisms, in mammals, there are two broad types of stem cells, embryonic stem cells, which are isolated from the inner cell mass of blastocysts, and adult stem cells, which are found in various tissues. In adult organisms, stem cells and progenitor cells act as a system for the body. There are three known accessible sources of adult stem cells in humans, Bone marrow, which requires extraction by harvesting. Adipose tissue, which requires extraction by liposuction, Stem cells can also be taken from umbilical cord blood just after birth. Of all stem cell types, autologous harvesting involves the least risk, by definition, autologous cells are obtained from ones own body, just as one may bank his or her own blood for elective surgical procedures. Adult stem cells are used in various medical therapies. Stem cells can now be artificially grown and transformed into specialized cell types with characteristics consistent with cells of tissues such as muscles or nerves. Embryonic cell lines and autologous stem cells generated through somatic cell nuclear transfer or dedifferentiation have also been proposed as promising candidates for future therapies. Research into stem cells grew out of findings by Ernest A. McCulloch, till at the University of Toronto in the 1960s. The classical definition of a cell requires that it possess two properties, Self-renewal, the ability to go through numerous cycles of cell division while maintaining the undifferentiated state. Potency, the capacity to differentiate into specialized cell types, apart from this it is said that stem cell function is regulated in a feed back mechanism. Stochastic differentiation, when one cell develops into two differentiated daughter cells, another stem cell undergoes mitosis and produces two stem cells identical to the original. Potency specifies the differentiation potential of the stem cell, totipotent stem cells can differentiate into embryonic and extraembryonic cell types. Such cells can construct a complete, viable organism and these cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the egg are also totipotent. Pluripotent stem cells are the descendants of totipotent cells and can differentiate into all cells. Multipotent stem cells can differentiate into a number of cell types, oligopotent stem cells can differentiate into only a few cell types, such as lymphoid or myeloid stem cells
29.
Cellular differentiation
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In developmental biology, cellular differentiation is the process where a cell changes from one cell type to another. Most commonly the cell changes to a specialized type. Differentiation occurs numerous times during the development of an organism as it changes from a simple zygote to a complex system of tissues. Differentiation continues in adulthood as adult stem cells divide and create fully differentiated daughter cells during tissue repair, some differentiation occurs in response to antigen exposure. Differentiation dramatically changes a cells size, shape, membrane potential, metabolic activity and these changes are largely due to highly controlled modifications in gene expression and are the study of epigenetics. With a few exceptions, cellular differentiation almost never involves a change in the DNA sequence itself, thus, different cells can have very different physical characteristics despite having the same genome. There are multiple levels of potency, the cells ability to differentiate into other cell types. A greater potency indicates a number of cells that can be derived. A cell that can differentiate into all types, including the placental tissue, is known as totipotent. In mammals, only the zygote and subsequent blastomeres are totipotent, a cell that can differentiate into all cell types of the adult organism is known as pluripotent. Such cells are called meristematic cells in plants and embryonic stem cells in animals. Virally induced expression of four transcription factors Oct4, Sox2, c-Myc, a multipotent cell is one that can differentiate into multiple different, but closely related cell types. Oligopotent cells are more restricted than multipotent, but can still differentiate into a few closely related cell types, finally, unipotent cells can differentiate into only one cell type, but are capable of self-renewal. In cytopathology, the level of differentiation is used as a measure of cancer progression. Grade is a marker of how differentiated a cell in a tumor is, three basic categories of cells make up the mammalian body, germ cells, somatic cells, and stem cells. Most cells are diploid, they have two copies of each chromosome, such cells, called somatic cells, make up most of the human body, such as skin and muscle cells. Cells differentiate to specialize for different functions, germ line cells are any line of cells that give rise to gametes—eggs and sperm—and thus are continuous through the generations. Stem cells, on the hand, have the ability to divide for indefinite periods
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Lymphopoiesis
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Lymphopoiesis is the generation of lymphocytes, one of the five types of white blood cell. It is more known as lymphoid hematopoiesis. Pathosis in lymphopoiesis leads to any of various disorders, such as the lymphomas. Lymphocytes are considered to be of the lineage as opposed to other lineages of blood cells such as the myeloid lineage. It is rare now for lymphopoiesis to refer to the creation of lymphatic tissues, and it gives insight into the nature of redundancy and overlap in the immune system and hints how to use this to advantage. The partial loss of or loss of function of any white blood cell type is a health matter. Were this system to fail, the body would be largely undefended from infection, examples of such cells are CFUs such as CFU-T. In mice, transplantation of a single cell can reconstitute a sub-lethally irradiated host with all these lineages of cells. This has been known for more than 40 years, lymphopoiesis continues throughout life and so progenitor cells and their parent stem cells must always be present. It is often not effective in preventing infections in the newborn, however early in gestation the developing embryo has begun its own lymphopoiesis from the fetal liver. Lymphopoiesis also arises from the yolk sac and this is in contrast to the adult where all lymphocytes originate in the bone marrow. There are four types of lymphocytes, many sub-types. All are generated by normal or abnormal lymphopoiesis except for certain artificial strains created in the laboratory by development from existing strains and this is hardly a simple topic. Lymphopoiesis can be viewed in a sense as a recursive process of cell division and also as a process of differentiation. Given that lymphocytes arise from specific types of limited stem cells - which we can call P cells - such cells can divide in several ways and these are general principles of limited stem cells. Considering the P as the cell, but not a true stem cell. Or the mother cell P may divide unequally into two new daughter cells both of which differ from other and also from the mother. Any daughter cell will usually have new specialized abilities and if it is able to divide it will form a new sub-lineage, the difference of a daughter cell from the mother may be great, but it could also be much less, even subtle
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Peyer's patch
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Peyers patches are organized lymphoid follicles, named after the 17th-century Swiss anatomist Johann Conrad Peyer. Peyers patches are observable as elongated thickenings of the intestinal epithelium measuring a few centimeters in length, about 100 are found in humans. Microscopically, Peyers patches appear as oval or round lymphoid follicles located in the layer of the ileum. The number of Peyers patches peaks at age 15–25 and then declines during adulthood, in the distal ileum, they are numerous and they form a lymphoid ring. At least 46% of Peyers patches are concentrated in the distal 25 cm of ileum in humans and it is important to note that there are large variations in size, shape, and distribution of Peyers patches from one individual to another one. In adults, B lymphocytes are seen to dominate the follicles germinal centers, T lymphocytes are found in the zones between follicles. Among the mononuclear cells, CD4+/CD25+ cells and CD8+/CD25+ cells are more abundant in Peyers patches than in the peripheral blood, Peyers patches are characterized by the follicle-associated epithelium, which covers every lymphoid follicles. Moreover, basal lamina of follicle-associated epithelium is more porous compare to intestinal villus, finally, follicle-associated epithelium is less permeable for ions and macromolecules, basically due to higher expression of tight junction proteins. Because the lumen of the tract is exposed to the external environment. Peyers patches thus establish their importance in the surveillance of the intestinal lumen. Peyers patches thus act for the system much as the tonsils act for the respiratory system, trapping foreign particles, surveilling them. Dendritic cells and macrophages can also sample the lumen by extending dendrites through transcellular M cell-specific pores. At the same time the paracellular pathway of follicle-associated epithelium is closed tightly to prevent penetration of antigens, T cells, B-cells and memory cells are stimulated upon encountering antigen in Peyers patches. These cells then pass to the lymph nodes where the immune response is amplified. The hypertrophy of Peyers patches has also associated with susceptibility to transmissible spongiform encephalopathies. Salmonella typhi and poliovirus also target this section of the intestine
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Lymphatic system
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The lymphatic system was first described in the seventeenth century independently by Olaus Rudbeck and Thomas Bartholin. Unlike the cardiovascular system, the system is not a closed system. The human circulatory system processes an average of 20 liters of blood per day through capillary filtration, roughly 17 litres of the filtered plasma are reabsorbed directly into the blood vessels, while the remaining three litres remain in the interstitial fluid. One of the functions of the lymph system is to provide an accessory return route to the blood for the surplus three litres. The other main function is that of defense in the immune system, lymph is very similar to blood plasma, it contains lymphocytes and other white blood cells. It also contains waste products and cellular debris together with bacteria, associated organs composed of lymphoid tissue are the sites of lymphocyte production. Lymphocytes are concentrated in the lymph nodes, the spleen and the thymus are also lymphoid organs of the immune system. The tonsils are lymphoid organs that are associated with the digestive system. Lymphoid tissues contain lymphocytes, and also other types of cells for support. Lymph is the fluid that is formed when interstitial fluid enters the lymphatic vessels of the lymphatic system. Eventually, the lymph vessels empty into the ducts, which drain into one of the two subclavian veins, near their junction with the internal jugular veins. The lymphatic system consists of lymphatic organs, a network of lymphatic vessels. The primary or central lymphoid organs generate lymphocytes from immature progenitor cells, the thymus and the bone marrow constitute the primary lymphoid organs involved in the production and early clonal selection of lymphocyte tissues. Bone marrow is responsible for both the creation of T cells and the production and maturation of B cells, from the bone marrow, B cells immediately join the circulatory system and travel to secondary lymphoid organs in search of pathogens. T cells, on the hand, travel from the bone marrow to the thymus. Mature T cells join B cells in search of pathogens, the other 95% of T cells begin a process of apoptosis, a form of programmed cell death. Secondary or peripheral lymphoid organs, which include lymph nodes and the spleen, maintain mature naive lymphocytes, the peripheral lymphoid organs are the sites of lymphocyte activation by antigens. Activation leads to clonal expansion and affinity maturation, mature lymphocytes recirculate between the blood and the peripheral lymphoid organs until they encounter their specific antigen
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Lymph node
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A lymph node or lymph gland, is an ovoid or kidney-shaped organ of the lymphatic system, and of the adaptive immune system, that is widely present throughout the body. They are linked by the vessels as a part of the circulatory system. Lymph nodes are major sites of B and T lymphocytes, Lymph nodes are important for the proper functioning of the immune system, acting as filters for foreign particles and cancer cells. Lymph nodes do not have a function, which is primarily dealt with by the liver. In the lymphatic system the lymph node is a secondary lymphoid organ, a lymph node is enclosed in a fibrous capsule and is made up of an outer cortex and an inner medulla. Lymph nodes also have clinical significance and they become inflamed or enlarged in various diseases which may range from trivial throat infections, to life-threatening cancers. The condition of the nodes is very important in cancer staging, which decides the treatment to be used. When swollen, inflamed or enlarged, lymph nodes can be hard, Lymph nodes are kidney or oval shaped and range in size from a few millimeters to about 1–2 cm long. Each lymph node is surrounded by a capsule, which extends inside the lymph node to form trabeculae. The substance of the node is divided into the outer cortex. The cortex is continuous around the medulla except where the medulla comes into contact with the hilum. Thin reticular fibers of reticular connective tissue, and elastin form a supporting meshwork called a reticulin inside the node, B cells, are mainly found in the outer where they are clustered together as follicular B cells in lymphoid follicles and the T cells are mainly in the paracortex. The number and composition of follicles can change especially when challenged by an antigen, elsewhere in the node, there are only occasional leucocytes. As part of the network there are follicular dendritic cells in the B cell follicle. The reticular network not only provides the support, but also the surface for adhesion of the dendritic cells. It allows exchange of material with blood through the high endothelial venules and provides the growth and regulatory factors necessary for activation and maturation of immune cells. All of these sinuses drain the filtered lymphatic fluid into the medullary sinuses and these vessels are smaller and dont allow the passage of the macrophages so that they remain contained to function within the lymph node. In the course of the lymph, lymphocytes may be activated as part of the immune response
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Antigen
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In immunology, an antigen is a molecule capable of inducing an immune response on the part of the host organism, though sometimes antigens can be part of the host itself. In other words, an antigen is any substance that causes a system to produce antibodies against it. In most cases, an antibody can bind one specific antigen, in some instances, however. An antigen is a molecule that binds to Ag-specific receptors, Antigens are usually peptides, polysaccharides or lipids. In general, molecules other than peptides qualify as antigens but not as immunogens since they cannot elicit a response on their own. Furthermore, for a peptide to induce a response it must be a large enough size. The term antigen originally described a structural molecule that specifically to an antibody. It expanded to refer to any molecule or a molecular fragment that can be recognized by highly variable antigen receptors of the adaptive immune system. The antigen may originate from within the body or from the external environment, antigen presenting cells present antigens in the form of peptides on histocompatibility molecules. The T cells of the immune system recognize the antigens. Depending on the antigen and the type of the histocompatibility molecule, for T-Cell Receptor recognition, the peptide must be processed into small fragments inside the cell and presented by a major histocompatibility complex. The antigen cannot elicit the immune response without the help of an immunologic adjuvant, similarly, the adjuvant component of vaccines plays an essential role in the activation of the innate immune system. An immunogen is a substance that is able to trigger a humoral and/or cell-mediated immune response and it first initiates an innate immune response, which then causes the activation of the adaptive immune response. An antigen binds the highly variable immunoreceptor products once these have been generated, all immunogen molecules are also antigens, although the reverse is not true. At the molecular level, an antigen can be characterized by its ability to bind to an antibodys variable Fab region, different antibodies have the potential to discriminate among specific epitopes present on the antigen surface. A hapten is a molecule that changes the structure of an antigenic epitope. In order to induce a response, it needs to be attached to a large carrier molecule such as a protein. Antigens are usually proteins and polysaccharides, and less frequently, lipids and this includes parts of bacteria, viruses, and other microorganisms
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. PMID 15807853.
