1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
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
8.
Macrophage
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These large phagocytes are found in essentially all tissues, where they patrol for potential pathogens by amoeboid movement. They take various forms throughout the body, but all are part of the mononuclear phagocyte system, besides phagocytosis, they play a critical role in nonspecific defense and also help initiate specific defense mechanisms by recruiting other immune cells such as lymphocytes. For example, they are important as antigen presenters to T cells, in humans, dysfunctional macrophages cause severe diseases such as chronic granulomatous disease that result in frequent infections. Beyond increasing inflammation and stimulating the system, macrophages also play an important anti-inflammatory role. Macrophages that encourage inflammation are called M1 macrophages, whereas those that decrease inflammation, human macrophages are about 21 micrometres in diameter and are produced by the differentiation of monocytes in tissues. They can be identified using flow cytometry or immunohistochemical staining by their expression of proteins such as CD14, CD40, CD11b, CD64, F4/80 /EMR1, lysozyme M, MAC-1/MAC-3. Macrophages were first discovered by Élie Metchnikoff, a Russian zoologist, when a monocyte enters damaged tissue through the endothelium of a blood vessel, a process known as the leukocyte extravasation, it undergoes a series of changes to become a macrophage. At some sites such as the testis, macrophages have shown to populate the organ through proliferation. Unlike short-lived neutrophils, macrophages survive longer in the body up to a maximum of several months, macrophages are professional phagocytes and are highly specialized in removal of dying or dead cells and cellular debris. This role is important in inflammation, as the early stages of inflammation are dominated by neutrophils. The neutrophils are at first attracted to a site, where they proliferate, when a macrophage ingests a pathogen, the pathogen becomes trapped in a phagosome, which then fuses with a lysosome. Within the phagolysosome, enzymes and toxic peroxides digest the pathogen, however, some bacteria, such as Mycobacterium tuberculosis, have become resistant to these methods of digestion. Typhoidal Salmonellae too induce their own phagocytosis by host macrophages in vivo, macrophages can digest more than 100 bacteria before they finally die due to their own digestive compounds. Macrophages are versatile cells that play many roles, as scavengers, they rid the body of worn-out cells and other debris. Along with dendritic cells, they are foremost among the cells present antigens. At the same time, they carry receptors for lymphokines that allow them to be activated into single-minded pursuit of microbes, after digesting a pathogen, a macrophage will present the antigen of the pathogen to the corresponding helper T cell. In some cases, pathogens are very resistant to adhesion by the macrophages, the antigen presentation on the surface of infected macrophages in a lymph node stimulates TH1 to proliferate. When a B-cell in the lymph node recognizes the same unprocessed surface antigen on the bacterium with its surface bound antibody, the processed antigen is then presented in MHCII on the surface of the B-cell
9.
Dendritic cell
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Dendritic cells are antigen-presenting cells of the mammalian immune system. Their main function is to process antigen material and present it on the surface to the T cells of the immune system. They act as messengers between the innate and the immune systems. Dendritic cells are present in tissues that are in contact with the external environment, such as the skin. They can also be found in a state in the blood. Once activated, they migrate to the nodes where they interact with T cells and B cells to initiate. At certain development stages they grow branched projections, the dendrites that give the cell its name, while similar in appearance, these are structures distinct from the dendrites of neurons. Immature dendritic cells are also called veiled cells, as they possess large cytoplasmic veils rather than dendrites, dendritic cells were first described by Paul Langerhans in the late nineteenth century. The term dendritic cells was coined in 1973 by Ralph M. Steinman, the morphology of dendritic cells results in a very large surface-to-volume ratio. That is, the cell has a very large surface area compared to the overall cell volume. The most common division of cells is myeloid vs. plasmacytoid, The markers BDCA-2, BDCA-3. Lymphoid and myeloid DCs evolve from lymphoid and myeloid precursors, respectively, the blood DCs are typically identified and enumerated in flow cytometry. Three types of DCs have been defined in human blood, the CD1c+ myeloid DCs, the CD141+ myeloid DCs and this represents the nomenclature proposed by the nomenclature committee of the International Union of Immunological Societies. Dendritic cells that circulate in blood do not have all the features of their counterparts in tissue. Still, they can perform functions including chemokine-production, cross-presentation. In some respects, dendritic cells cultured in vitro do not show the behaviour or capability as dendritic cells isolated ex vivo. Nonetheless, they are used for research as they are still much more readily available than genuine DCs. Mo-DC or MDDC refers to cells matured from monocytes HP-DC refers to cells derived from hematopoietic progenitor cells, while humans and non-human primates such as rhesus macaques appear to have DCs divided into these groups, other species have different subdivisions of DCs
10.
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
11.
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
12.
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
13.
Human
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Modern humans are the only extant members of Hominina tribe, a branch of the tribe Hominini belonging to the family of great apes. Several of these hominins used fire, occupied much of Eurasia and they began to exhibit evidence of behavioral modernity around 50,000 years ago. In several waves of migration, anatomically modern humans ventured out of Africa, the spread of humans and their large and increasing population has had a profound impact on large areas of the environment and millions of native species worldwide. Humans are uniquely adept at utilizing systems of communication for self-expression and the exchange of ideas. Humans create complex structures composed of many cooperating and competing groups, from families. Social interactions between humans have established a wide variety of values, social norms, and rituals. These human societies subsequently expanded in size, establishing various forms of government, religion, today the global human population is estimated by the United Nations to be near 7.5 billion. In common usage, the word generally refers to the only extant species of the genus Homo—anatomically and behaviorally modern Homo sapiens. In scientific terms, the meanings of hominid and hominin have changed during the recent decades with advances in the discovery, there is also a distinction between anatomically modern humans and Archaic Homo sapiens, the earliest fossil members of the species. The English adjective human is a Middle English loanword from Old French humain, ultimately from Latin hūmānus, the words use as a noun dates to the 16th century. The native English term man can refer to the species generally, the species binomial Homo sapiens was coined by Carl Linnaeus in his 18th century work Systema Naturae. The generic name Homo is a learned 18th century derivation from Latin homō man, the species-name sapiens means wise or sapient. Note that the Latin word homo refers to humans of either gender, the genus Homo evolved and diverged from other hominins in Africa, after the human clade split from the chimpanzee lineage of the hominids branch of the primates. The closest living relatives of humans are chimpanzees and gorillas, with the sequencing of both the human and chimpanzee genome, current estimates of similarity between human and chimpanzee DNA sequences range between 95% and 99%. The gibbons and orangutans were the first groups to split from the leading to the humans. The splitting date between human and chimpanzee lineages is placed around 4–8 million years ago during the late Miocene epoch, during this split, chromosome 2 was formed from two other chromosomes, leaving humans with only 23 pairs of chromosomes, compared to 24 for the other apes. There is little evidence for the divergence of the gorilla, chimpanzee. Each of these species has been argued to be an ancestor of later hominins
14.
Blood
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Blood is a body fluid in humans and other animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells. In vertebrates, it is composed of blood cells suspended in blood plasma, plasma, which constitutes 55% of blood fluid, is mostly water, and contains dissipated proteins, glucose, mineral ions, hormones, carbon dioxide, and blood cells themselves. Albumin is the protein in plasma, and it functions to regulate the colloidal osmotic pressure of blood. The blood cells are red blood cells, white blood cells. The most abundant cells in blood are red blood cells. These contain hemoglobin, a protein, which facilitates oxygen transport by reversibly binding to this respiratory gas. In contrast, carbon dioxide is mostly transported extracellularly as bicarbonate ion transported in plasma, vertebrate blood is bright red when its hemoglobin is oxygenated and dark red when it is deoxygenated. Some animals, such as crustaceans and mollusks, use hemocyanin to carry oxygen, insects and some mollusks use a fluid called hemolymph instead of blood, the difference being that hemolymph is not contained in a closed circulatory system. In most insects, this blood does not contain oxygen-carrying molecules such as hemoglobin because their bodies are small enough for their system to suffice for supplying oxygen. Jawed vertebrates have an immune system, based largely on white blood cells. White blood cells help to resist infections and parasites, platelets are important in the clotting of blood. Arthropods, using hemolymph, have hemocytes as part of their immune system, Blood is circulated around the body through blood vessels by the pumping action of the heart. Medical terms related to blood often begin with hemo- or hemato- from the Greek word αἷμα for blood. In terms of anatomy and histology, blood is considered a form of connective tissue, given its origin in the bones. The average adult has a volume of roughly 5 litres. These blood cells consist of erythrocytes, leukocytes, and thrombocytes, by volume, the red blood cells constitute about 45% of whole blood, the plasma about 54. 3%, and white cells about 0. 7%. Whole blood exhibits non-Newtonian fluid dynamics, if all human hemoglobin were free in the plasma rather than being contained in RBCs, the circulatory fluid would be too viscous for the cardiovascular system to function effectively. One microliter of blood contains,4.7 to 6.1 million,4.2 to 5.4 million erythrocytes, Red blood cells contain the bloods hemoglobin, mature red blood cells lack a nucleus and organelles in mammals
15.
Amoeba
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An amoeba, often called amoeboid, is a type of cell or organism which has the ability to alter its shape, primarily by extending and retracting pseudopods. Amoebas do not form a taxonomic group, instead, they are found in every major lineage of eukaryotic organisms. Amoeboid cells occur not only among the protozoa, but also in fungi, algae, microbiologists often use the terms amoeboid and amoeba interchangeably for any organism that exhibits amoeboid movement. In older classification systems, most amoebas were placed in the class or subphylum Sarcodina, however, molecular phylogenetic studies have shown that Sarcodina is not a monophyletic group whose members share common descent. Consequently, amoeboid organisms are no longer classified together in one group, the best known amoeboid protists are the Giant Amoebae Chaos carolinense and Amoeba proteus, both of which are widely cultivated and studied in classrooms and laboratories. Amoebae move and feed by using pseudopods, which are bulges of cytoplasm formed by the action of actin microfilaments pushing out the plasma membrane that surrounds the cell. The appearance and internal structure of pseudopods are used to distinguish groups of amoebae from one another, amoebozoan species, such as those in the genus Amoeba, typically have bulbous pseudopods, rounded at the ends and roughly tubular in cross-section. Cercozoan amoeboids, such as Euglypha and Gromia, have slender, foraminifera emit fine, branching pseudopods that merge with one another to form net-like structures. Some groups, such as the Radiolaria and Heliozoa, have stiff, needle-like, free-living amoebae may be testate, or naked. The shells of testate amoebae may be composed of substances, including calcium, silica, chitin, or agglutinations of found materials like small grains of sand. To regulate osmotic pressure, most freshwater amoebae have a contractile vacuole which expels excess water from the cell and this organelle is necessary because freshwater has a lower concentration of solutes than the amoebas own internal fluids. Because the surrounding water is hypotonic with respect to the contents of the cell, without a contractile vacuole, the cell would fill with excess water and, eventually, burst. Marine amoebae do not usually possess a contractile vacuole, because the concentration of solutes within the cell are in balance with the tonicity of the surrounding water, the food sources of amoebae vary. Some amoebae are predatory and live by consuming bacteria and other protists, Some are detritivores and eat dead organic material. Amoebae typically ingest their food by phagocytosis, extending pseudopods to encircle, Amoeboid cells do not have a mouth or cytostome, and there is no fixed place on the cell at which phagocytosis normally occurs. Some amoebae also feed by pinocytosis, imbibing dissolved nutrients through vesicles formed within the cell membrane, the size of amoeboid cells and species is extremely variable. The marine amoeboid Massisteria voersi is just 2.3 to 3 micrometres in diameter, at the other extreme, the shells of deep-sea xenophyophores can attain 20 cm in diameter. Some multicellular organisms have amoeboid cells only in certain phases of life, in the immune system of humans and other animals, amoeboid white blood cells pursue invading organisms, such as bacteria and pathogenic protists, and engulf them by phagocytosis
16.
Cytoplasm
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In cell biology, the cytoplasm is the material within a living cell, excluding the cell nucleus. It comprises cytosol and the organelles – the cells internal sub-structures, all of the contents of the cells of prokaryotic organisms are contained within the cytoplasm. Within the cells of organisms the contents of the cell nucleus are separated from the cytoplasm. The cytoplasm is about 80% water and usually colorless, the submicroscopic ground cell substance or cytoplasmatic matrix which remains after exclusion the cell organelles and particles is groundplasm. It is within the cytoplasm that most cellular activities occur, such as many metabolic pathways including glycolysis, the concentrated inner area is called the endoplasm and the outer layer is called the cell cortex or the ectoplasm. Movement of calcium ions in and out of the cytoplasm is an activity for metabolic processes. In plants, movement of the cytoplasm around vacuoles is known as cytoplasmic streaming, the term was introduced by Rudolf von Kölliker in 1863, originally as a synonym for protoplasm, but later it has come to mean the cell substance and organelles outside the nucleus. There has been disagreement on the definition of cytoplasm, as some authors prefer to exclude from it some organelles. The physical properties of the cytoplasm have been contested in recent years and it remains uncertain how the varied components of the cytoplasm interact to allow movement of particles and organelles while maintaining the cell’s structure. The flow of cytoplasmic components plays an important role in cellular functions which are dependent on the permeability of the cytoplasm. An example of function is cell signalling, a process which is dependent on the manner in which signaling molecules are allowed to diffuse across the cell. While small signaling molecules like calcium ions are able to diffuse with ease, larger molecules, the irregular dynamics of such particles have given rise to various theories on the nature of the cytoplasm. There has long been evidence that the cytoplasm behaves like a sol-gel and it is thought that the component molecules and structures of the cytoplasm behave at times like a disordered colloidal solution and at other times like an integrated network, forming a solid mass. Recently it has proposed that the cytoplasm behaves like a glass-forming liquid approaching the glass transition. A cells ability to vitrify in the absence of activity, as in dormant periods. There has been examining the motion of cytoplasmic particles independent of the nature of the cytoplasm. In such an approach, the aggregate random forces within the cell caused by motor proteins explain the non-Brownian motion of cytoplasmic constituents. The three major elements of the cytoplasm are the cytosol, organelles and inclusions, the cytosol is the portion of the cytoplasm not contained within membrane-bound organelles
17.
Granulocyte
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Granulocytes are a category of white blood cells characterized by the presence of granules in their cytoplasm. They are also called polymorphonuclear leukocytes because of the shapes of the nucleus. This distinguishes them from the mononuclear agranulocytes, in common parlance, the term polymorphonuclear leukocyte often refers specifically to neutrophil granulocytes, the most abundant of the granulocytes, the other types have lower numbers. Granulocytes are produced via granulopoiesis in the bone marrow, neutrophils are normally found in the bloodstream and are the most abundant type of phagocyte, constituting 50% to 60% of the total circulating white blood cells. One litre of blood contains about five billion neutrophils, which are about 12–15 micrometers in diameter. Once neutrophils have received the signals, it takes them about thirty minutes to leave the blood. Neutrophils do not return to the blood, they turn into pus cells, mature neutrophils are smaller than monocytes, and have a segmented nucleus with several sections, each section is connected by chromatin filaments. Neutrophils do not normally exit the bone marrow until maturity, neutrophils have three strategies for directly attacking micro-organisms, phagocytosis, release of soluble anti-microbials, and generation of neutrophil extracellular traps. Neutrophils are professional phagocytes, they are ferocious eaters and rapidly engulf invaders coated with antibodies and complement, the intracellular granules of the human neutrophil have long been recognized for their protein-destroying and bactericidal properties. Neutrophils can secrete products that stimulate monocytes and macrophages, these secretions increase phagocytosis, neutrophils have two types of granules, primary granules and secondary granules. In addition, secretions from the granules of neutrophils stimulate the phagocytosis of IgG antibody-coated bacteria. The secondary granules contain compounds that are involved in the formation of oxygen compounds, lysozyme. Neutrophil extracellular traps comprise a web of fibers composed of chromatin and serine proteases that trap, trapping of bacteria is a particularly important role for NETs in sepsis, where NET are formed within blood vessels. Eosinophils also have kidney-shaped lobed nuclei, the number of granules in an eosinophil can vary because they have a tendency to degranulate while in the blood stream. A polypeptide called interleukin-5 interacts with eosinophils and causes them to grow and differentiate, basophils are one of the least abundant cells in bone marrow and blood. Like neutrophils and eosinophils, they have lobed nuclei, however, basophils have receptors that can bind to IgE, IgG, complement, and histamine. The cytoplasm of basophils contains an amount of granules, these granules are usually numerous enough to partially conceal the nucleus. Granule contents of basophils are abundant with histamine, heparin, chondroitin sulfate, peroxidase, platelet-activating factor, when an infection occurs, mature basophils will be released from the bone marrow and travel to the site of infection
18.
Inflammation
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The classical signs of inflammation are heat, pain, redness, swelling, and loss of function. Inflammation is a response, and therefore it is considered as a mechanism of innate immunity, as compared to adaptive immunity. Too little inflammation could lead to tissue destruction by the harmful stimulus. In contrast, chronic inflammation may lead to a host of diseases, such as hay fever, periodontitis, atherosclerosis, rheumatoid arthritis, Inflammation is therefore normally closely regulated by the body. Inflammation can be classified as acute or chronic. Acute inflammation is the response of the body to harmful stimuli and is achieved by the increased movement of plasma. A series of biochemical events propagates and matures the inflammatory response, involving the vascular system, the immune system. Inflammation is not a synonym for infection, Inflammation on the other hand describes purely the bodys immunovascular response, whatever the cause may be. But because of how often the two are correlated, words ending in the suffix -itis are sometimes described as referring to infection. There are also situations where microbial invasion does not result in classic inflammatory response—for example, parasitosis. Acute inflammation is a process, usually appearing within a few minutes or hours. It involves a coordinated and systemic mobilisation response locally of various immune, endocrine, in a normal healthy response, it becomes activated, clears the pathogen and begins a repair process and then ceases. It is characterized by five signs, An acronym that may be used to remember the key symptoms is PRISH, for pain, redness, immobility, swelling. Loss of function has multiple causes, Acute inflammation of the lung does not cause pain unless the inflammation involves the parietal pleura, which does have pain-sensitive nerve endings. PAMPs are compounds that are associated with pathogens, but which are distinguishable from host molecules. DAMPs are compounds that are associated with host-related injury and cell damage, at the onset of an infection, burn, or other injuries, these cells undergo activation and release inflammatory mediators responsible for the clinical signs of inflammation. Vasodilation and its resulting increased blood flow causes the redness and increased heat, increased permeability of the blood vessels results in an exudation of plasma proteins and fluid into the tissue, which manifests itself as swelling. Some of the released mediators such as increase the sensitivity to pain
19.
Foam cell
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Foam cells are the fat-laden M2 macrophages seen in atherosclerosis. They are an indication of plaque build-up, or atherosclerosis, which is associated with increased risk of heart attack. Foam cells are formed when the body sends macrophages to the location of a fatty deposit on the vessel walls. The macrophage surrounds the fatty material in an attempt to destroy it, the cell becomes filled with lipids. The lipids surrounded by the macrophage give it a foamy appearance, in chronic hyperlipidemia, lipoproteins aggregate within the intima of blood vessels and become oxidized by the action of oxygen free radicals generated either by macrophages or endothelial cells. The macrophages engulf oxidized low-density lipoproteins by endocytosis via scavenger receptors, the oxidized LDL accumulates in the macrophages and other phagocytes, which are then known as foam cells. Foam cells form the fatty streaks of the plaques of atheroma in the intima of arteries. Low-density lipoprotein cholesterol is contained by a foam cell, LDL is also known as bad cholesterol. It becomes a marker for atherosclerosis, foam cells are the bodys way of trying to get rid of bad cholesterol from the blood vessels. Foam cells do not give off any explicit signs or symptoms, foam cells are very small in size and can only be truly detected by examining a fatty plaque under a microscope after it is removed from the body. HDL cholesterol is good cholesterol and it removes harmful bad cholesterol from where it does not belong, foam cells are not dangerous as such, but can become a problem when they accumulate at particular foci thus creating a necrotic centre of atherosclerosis. If the fibrous cap that prevents the necrotic centre from spilling into the lumen of a vessel ruptures, the occlusion of small vessels results in ischemia, and contributes to stroke and myocardial infarction, two of the leading causes of cardiovascular-related death. Atherosclerosis is the hardening and narrowing of the arteries, due to the formation of plaques in the blood vessel, atherosclerosis is the usual cause of heart attacks, strokes, and peripheral vascular disease. Together, these diseases are called cardiovascular disease, autoimmunity occurs when the body starts attacking itself. The link between atherosclerosis and autoimmunity is plasmacytoid dendritic cells, pDCs contribute to the early stages of the formation of atherosclerotic lesions in the blood vessels. Stimulation of pDCs leads to an increase of macrophages present in plaques, foamy macrophages are also found in diseases caused by pathogens that persist in the body, such as Chlamydia, Toxoplasma, or Mycobacterium tuberculosis. In tuberculosis, bacterial lipids disable macrophages from pumping out excess LDL, the cholesterol forms a rich food source for the bacteria. As the macrophages die, the mass of cholesterol in the center of the granuloma becomes a cheesy substance called caseum, foam cells may form around leaked silicone from breast implants, inhaled organic antigens and some drugs
20.
CD14
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CD14, also known as CD14, is a human gene. The protein encoded by this gene is a component of the immune system. CD14 exists in two forms, one anchored to the membrane by a tail, the other a soluble form. Soluble CD14 either appears after shedding of mCD14 or is directly secreted from intracellular vesicles, the x-ray crystal structure of human CD14 reveals a monomeric, bent solenoid structure containing a hydrophobic amino-terminal pocket. CD14 was the first described pattern recognition receptor, CD14 acts as a co-receptor for the detection of bacterial lipopolysaccharide. CD14 can bind LPS only in the presence of lipopolysaccharide-binding protein, although LPS is considered its main ligand, CD14 also recognizes other pathogen-associated molecular patterns such as lipoteichoic acid. CD14 is expressed mainly by macrophages and by neutrophils and it is also expressed by dendritic cells. The soluble form of the receptor is secreted by the liver, mCD14 and sCD14 are also present on enterocytes. SCD14 is also present in milk, where it is believed to regulate microbial growth in the infant gut. CD14+ monocytes can differentiate into a host of different cells, including dendritic cells, CD14 has been shown to interact with lipopolysaccharide-binding protein. Human CD14 genome location and CD14 gene details page in the UCSC Genome Browser, CD14 Antigens at the US National Library of Medicine Medical Subject Headings
21.
Interleukin 12
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Interleukin 12 is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells in response to antigenic stimulation. IL-12 is composed of a bundle of four alpha helices and it is a heterodimeric cytokine encoded by two separate genes, IL-12A and IL-12B. The active heterodimer, and a homodimer of p40 are formed following protein synthesis, IL-12 is involved in the differentiation of naive T cells into Th1 cells. It is known as a T cell-stimulating factor, which can stimulate the growth and it stimulates the production of interferon-gamma and tumor necrosis factor-alpha from T cells and natural killer cells, and reduces IL-4 mediated suppression of IFN-γ. T cells that produce IL-12 have a coreceptor, CD30, which is associated with IL-12 activity, IL-12 plays an important role in the activities of natural killer cells and T lymphocytes. IL-12 mediates enhancement of the activity of NK cells and CD8+ cytotoxic T lymphocytes. There also seems to be a link between IL-2 and the transduction of IL-12 in NK cells. IL-2 stimulates the expression of two IL-12 receptors, IL-12R-β1 and IL-12R-β2, maintaining the expression of a protein involved in IL-12 signaling in NK cells. Enhanced functional response is demonstrated by IFN-γ production and killing of target cells, IL-12 also has anti-angiogenic activity, which means it can block the formation of new blood vessels. It does this by increasing production of gamma, which in turn increases the production of a chemokine called inducible protein-10. IP-10 then mediates this anti-angiogenic effect, because of its ability to induce immune responses and its anti-angiogenic activity, there has been an interest in testing IL-12 as a possible anti-cancer drug. However, it has not been shown to have activity in the tumors tested to this date. There is a link that may be useful in treatment between IL-12 and the diseases psoriasis & inflammatory bowel disease, IL-12 binds to the IL-12 receptor, which is a heterodimeric receptor formed by IL-12R-β1 and IL-12R-β2. Upon binding, IL-12R-β2 becomes tyrosine phosphorylated and provides binding sites for kinases and these are important in activating critical transcription factor proteins such as STAT4 that are implicated in IL-12 signaling in T cells and NK cells. This pathway is known as the JAK-STAT pathway, administration of IL-12 to people suffering from autoimmune diseases was shown to worsen the autoimmune phenomena. This is believed to be due to its key role in induction of Th1 immune responses, in contrast, IL-12 gene knock-out in mice or a treatment of mice with IL-12 specific antibodies ameliorated the disease. Further investigation is underway, to whether the results found in mice are as profound in humans. Interleukin 12 is produced by activated antigen-presenting cells and it promotes the development of Th1 responses and is a powerful inducer of IFNγ production by T and NK cells
22.
CD4
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In molecular biology, CD4 is a glycoprotein found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was known as leu-3. In humans, the CD4 protein is encoded by the CD4 gene, CD4+ T helper cells are white blood cells that are an essential part of the human immune system. They are often referred to as CD4 cells, T-helper cells or T4 cells and they are called helper cells because one of their main roles is to send signals to other types of immune cells, including CD8 killer cells, which then destroy the infectious particle. Like many cell surface receptors/markers, CD4 is a member of the immunoglobulin superfamily and it has four immunoglobulin domains that are exposed on the extracellular surface of the cell, D1 and D3 resemble immunoglobulin variable domains. D2 and D4 resemble immunoglobulin constant domains, CD4 uses its D1 domain to interact with the β2-domain of MHC class II molecules. T cells expressing CD4 molecules on their surface, therefore, are specific for antigens presented by MHC II, MHC class I contains Beta-2 microglobulin. The short cytoplasmic/intracellular tail of CD4 contains a sequence of amino acids that allow it to interact with the lck molecule. CD4 is a co-receptor that assists the T cell receptor in communicating with an antigen-presenting cell, various types of T helper cells are thereby produced. CD4 also interacts directly with MHC class II molecules on the surface of the cell using its extracellular domain. The extracellular domain adopts an immunoglobulin-like beta-sandwich with seven strands in 2 beta sheets, during antigen presentation, both the TCR complex and CD4 are recruited to bind to different regions of the MHCII molecule. CD4 has also shown to interact with SPG21, Lck. HIV-1 uses CD4 to gain entry into host T-cells and achieves this through its viral envelope protein known as gp120, the binding to CD4 creates a shift in the conformation of gp120 allowing HIV-1 to bind to a co-receptor expressed on the host cell. These co-receptors are chemokine receptors CCR5 or CXCR4, following a structural change in another viral protein, HIV inserts a fusion peptide into the host cell that allows the outer membrane of the virus to fuse with the cell membrane. HIV infection leads to a reduction in the number of T cells expressing CD4. A CD4 count measures the number of T cells expressing CD4, while CD4 counts are not a direct HIV test—e. g. They do not check the presence of viral DNA, or specific antibodies against HIV—they are used to assess the system of a patient. Medical professionals also refer to CD4 tests to determine efficacy of treatment, viral load testing provides more information about the efficacy for therapy than CD4 counts
23.
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
24.
Monoblast
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Monoblasts are normally found in bone marrow and do not appear in the normal peripheral blood. They mature into monocytes which, in turn, develop into macrophages. A typical monoblast is about 12 to 20 µm in diameter, has a nuclear to cytoplasm ratio of 4,1 to 3,1, one to four nucleoli are usually visible. The nucleus can be central or eccentric and it can show evidence of indentation or folding, the cytoplasm is agranular, stains moderately to lightly basophilic, and often has an intensely stained periphery and a prominent perinuclear zone. The monoblast is the first stage of monocyte-macrophage maturation, the developmental stages of the monoblast are, CFU-GM -> monoblast -> promonocyte -> monocyte-> macrophage. Monocyte Macrophage Agranulocyte White blood cell
25.
Hematopoietic stem cell
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Hematopoietic stem cells or hemocytoblasts are the stem cells that give rise to all the other blood cells through the process of haematopoiesis. They are derived from mesoderm and located in the red bone marrow, HSCs give rise to both the myeloid and lymphoid lineages of blood cells. The definition of hematopoietic stem cells has evolved since HSCs were first discovered in 1961, the hematopoietic tissue contains cells with long-term and short-term regeneration capacities and committed multipotent, oligopotent, and unipotent progenitors. HSCs constitute 1,10.000 of cells in myeloid tissue, HSC studies through much of the past half century have led to a much deeper understanding. More recent advances have resulted in the use of HSC transplants in the treatment of cancers, HSCs are found in the bone marrow of adults, especially in the pelvis, femur, and sternum. They are also found in cord blood and, in small numbers. Stem and progenitor cells can be taken from the pelvis, at the iliac crest, using a needle, the cells can be removed as liquid or they can be removed via a core biopsy. In mammalian embryology, the first definitive HSCs are detected in the AGM, HSCs can replenish all blood cell types and self-renew. A small number of HSCs can expand to generate a large number of daughter HSCs. This phenomenon is used in bone marrow transplantation, when a number of HSCs reconstitute the hematopoietic system. This process indicates that, subsequent to bone marrow transplantation, symmetrical cell divisions into two daughter HSCs must occur. Stem cell self-renewal is thought to occur in the stem cell niche in the bone marrow and it was originally believed that all HSCs were alike in their self-renewal and differentiation abilities. The results of these studies led to the notion of lineage bias. Using the ratio ρ = L / M of lymphoid to myeloid cells in blood as a quantitative marker, balanced HSCs repopulate peripheral white blood cells in the same ratio of myeloid to lymphoid cells as seen in unmanipulated mice. Myeloid-biased HSCs give rise to very few lymphocytes resulting in ratios 0 < ρ <3, while lymphoid-biased HSCs generate very few myeloid cells, all three types are normal types of HSC, and they do not represent stages of differentiation. Rather, these are three classes of HSC, each with an epigenetically fixed differentiation program and these studies also showed that lineage bias is not stochastically regulated or dependent on differences in environmental influence. My-bi HSC self-renew longer than balanced or Ly-bi HSC, the myeloid bias results from reduced responsiveness to the lymphopoetin interleukin 7. Subsequently, other groups confirmed and highlighted the original findings, for example, the Eaves group confirmed in 2007 that repopulation kinetics, long-term self-renewal capacity, and My-bi and Ly-bi are stably inherited intrinsic HSC properties
26.
Red pulp
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The red pulp of the spleen is composed of connective tissue known as the cords of Billroth and many splenic sinuses that are engorged with blood, giving it a red color. Its primary function is to filter the blood of antigens, microorganisms, the spleen is made of red pulp and white pulp, separated by the marginal zone, 76-79% of a normal spleen is red pulp. Unlike white pulp, which mainly contains lymphocytes such as T cells, red pulp is made up of different types of blood cells, including platelets, granulocytes, red blood cells. The splenic sinuses of the spleen, also known as sinusoids, are wide vessels that drain into trabecular veins, gaps in the endothelium lining the sinusoids mechanically filter blood cells as they enter the spleen. Worn-out or abnormal red cells attempting to squeeze through the intercellular spaces become badly damaged. In addition to aged red blood cells, the sinusoids also filter out particles that could clutter up the bloodstream, such as remnants, platelets. Red pulp consists of a network of fine reticular fiber, continuous with those of the splenic trabeculae, to which are applied flat. The meshes of the reticulum are filled with blood, White corpuscles are found to be in proportion than they are in ordinary blood. Large rounded cells, termed splenic cells, are seen, these are capable of ameboid movement. In the young spleen, macrophages may also be found, each containing numerous nuclei or one compound nucleus, nucleated red-blood corpuscles have also been found in the spleen of young animals. In lymphoid leukemia, the pulp of the spleen hypertrophies. In some cases the white pulp can swell to 50% of the volume of the spleen. In myeloid leukemia, the white pulp atrophies and the red pulp expands and this article incorporates text in the public domain from the 20th edition of Grays Anatomy Anatomy Atlases - Microscopic Anatomy, plate 09.175 - Spleen, Red Pulp
27.
Blood cell
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A blood cell, also called a haematopoietic cell, hemocyte, or hematocyte, is a cell produced through hematopoiesis and found mainly in the blood. Red blood cells – Erythrocytes White blood cells – Leukocytes Platelets – Thrombocytes, together, these three kinds of blood cells add up to a total 45% of the blood tissue by volume, with the remaining 55% of the volume composed of plasma, the liquid component of blood. The volume percentage of red cells in the blood is measured by centrifuge or flow cytometry and is 45% of cells to total volume in males. Haemoglobin is an protein that facilitates transportation of oxygen from the lungs to tissues. Red blood cells or erythrocytes, primarily oxygen and collect carbon dioxide through the use of haemoglobin. In the process of being formed they go through a unipotent stem cell stage and they have the job alongside the white blood cells of protecting the healthy cells. RBCs are formed in the red marrow in the adults. After the completion of their lifespan, they are destroyed in the spleen, White blood cells or leukocytes, are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five diverse types of leukocytes exist, and are all produced and derived from multipotent cells in the bone known as a hematopoietic stem cells. They live for about 3 to 4 days in the human body. Leukocytes are found throughout the body, including the blood and lymphatic system, the two main categories of white blood cells are granulocytes and agranulocytes. Neutrophils are the most abundant of all the WBCs, Platelets, or thrombocytes or yellow blood cells, are very small, irregularly shaped clear cell fragments, 2–3 µm in diameter, which derive from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days, Platelets are a natural source of growth factors. They circulate in the blood of mammals and are involved in hemostasis, Platelets release thread-like fibers to form these clots. If the number of platelets is too low, excessive bleeding can occur, an abnormality or disease of the platelets is called a thrombocytopathy, which can be either a low number of platelets, a decrease in function of platelets, or an increase in the number of platelets. Platelets release a multitude of factors including Platelet-derived growth factor, a potent chemotactic agent, and TGF beta. Both of these factors have been shown to play a significant role in the repair. Local application of factors in increased concentrations through Platelet-rich plasma has been used as an adjunct to wound healing for several decades
28.
Vesicle (biology and chemistry)
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In cell biology, a vesicle is a small structure within a cell, consisting of fluid enclosed by a lipid bilayer. Vesicles form naturally during the processes of secretion, uptake and transport of materials within the cytoplasm, alternatively, they may be prepared artificially, in which case they are called liposomes. If there is only one phospholipid bilayer, they are called unilamellar liposome vesicles, the membrane enclosing the vesicle is also a lamellar phase, similar to that of the plasma membrane and vesicles can fuse with the plasma membrane to release their contents outside the cell. Vesicles can also fuse with other organelles within the cell, vesicles perform a variety of functions. Because it is separated from the cytosol, the inside of the vesicle can be made to be different from the cytosolic environment, for this reason, vesicles are a basic tool used by the cell for organizing cellular substances. Vesicles are involved in metabolism, transport, buoyancy control, and temporary storage of food and they can also act as chemical reaction chambers. Vesicle dysfunction is thought to contribute to Alzheimers disease, diabetes, some cases of epilepsy, some cancers and immunological disorders. Vacuoles are vesicles which contain mostly water, plant cells have a large central vacuole in the center of the cell that is used for osmotic control and nutrient storage. Contractile vacuoles are found in protists, especially those in Phylum Ciliophora. These vacuoles take water from the cytoplasm and excrete it from the cell to avoid bursting due to osmotic pressure, lysosomes are involved in cellular digestion. Food can be taken from outside the cell into food vacuoles by a process called endocytosis and these food vacuoles fuse with lysosomes which break down the components so that they can be used in the cell. This form of eating is called phagocytosis. Lysosomes are also used to destroy defective or damaged organelles in a process called autophagy and they fuse with the membrane of the damaged organelle, digesting it. Transport vesicles can move molecules between locations inside the cell, e. g. proteins from the endoplasmic reticulum to the Golgi apparatus. Membrane-bound and secreted proteins are made on ribosomes found in the endoplasmic reticulum. Most of these proteins mature in the Golgi apparatus before going to their destination which may be to lysosomes, peroxisomes. These proteins travel within the cell inside of transport vesicles, secretory vesicles contain materials that are to be excreted from the cell. Cells have many reasons to excrete materials, one reason is to dispose of wastes
29.
Granulocyte-macrophage colony-stimulating factor
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The pharmaceutical analogs of naturally occurring GM-CSF are called sargramostim and molgramostim. Unlike granulocyte colony-stimulating factor, which specifically promotes neutrophil proliferation and maturation, GM-CSF affects more cell types, especially macrophages, GM-CSF is a monomeric glycoprotein that functions as a cytokine - it is a white blood cell growth factor. GM-CSF stimulates stem cells to produce granulocytes and monocytes, monocytes exit the circulation and migrate into tissue, whereupon they mature into macrophages and dendritic cells. Thus, it is part of the cascade, by which activation of a small number of macrophages can rapidly lead to an increase in their numbers. GM-CSF also has effects on mature cells of the immune system. These include, for example, inhibiting neutrophil migration and causing an alteration of the receptors expressed on the cells surface, GM-CSF signals via signal transducer and activator of transcription, STAT5. In macrophages, it has also shown to signal via STAT3. The cytokine activates macrophages to inhibit fungal survival and it induces deprivation in intracellular free zinc and increases production of reactive oxygen species that culminate in fungal zinc starvation and toxicity. Thus, GM-CSF facilitates development of the system and promotes defense against infections. GM-CSF also plays a role in development by functioning as an embryokine produced by reproductive tract. Genes in the cluster include those encoding interleukins 4,5, human granulocyte macrophage colony-stimulating factor is glycosylated in its mature form. GM-CSF is manufactured using recombinant DNA technology and is marketed as a protein therapeutic called molgramostim or and it is used as a medication to stimulate the production of white blood cells and thus prevent neutropenia following chemotherapy. GM-CSF has also evaluated in clinical trials for its potential as a vaccine adjuvant in HIV-infected patients. In November 1996, the FDA also approved sargramostim for treatment of fungal infections, a liquid formulation was approved in 1995. Immunex was acquired by Amgen in 2002, as part of the acquisition, Leukine was spun off to Berlex, which became Bayer HealthCare in 2007. In 2009, Genzyme acquired the rights to Leukine from Bayer, GM-CSF is found in high levels in joints with rheumatoid arthritis and blocking GM-CSF may reduce the inflammation or damage. Some drugs are being developed to block GM-CSF
30.
Interleukin 4
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The interleukin 4 is a cytokine that induces differentiation of naive helper T cells to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4 in a feedback loop. The cell that initially produces IL-4, thus inducing Th0 differentiation, has not been identified and it is closely related and has functions similar to Interleukin 13. IL-4 has many roles, including the stimulation of activated B-cell and T-cell proliferation. It is a key regulator in humoral and adaptive immunity, IL-4 induces B-cell class switching to IgE, and up-regulates MHC class II production. IL-4 decreases the production of Th1 cells, macrophages, IFN-gamma, overproduction of IL-4 is associated with allergies. Tissue macrophages play an important role in inflammation and wound repair. The presence of IL-4 in extravascular tissues promotes alternative activation of macrophages into M2 cells, an increase in repair macrophages is coupled with secretion of IL-10 and TGF-β that result in a diminution of pathological inflammation. Release of arginase, proline, polyaminases and TGF-β by the activated M2 cell is tied with wound repair, the receptor for Interleukin-4 is known as the IL-4Rα. This receptor exists in 3 different complexes throughout the body, type 1 receptors are composed of the IL-4Rα subunit with a common γ chain and specifically bind IL-4. Type 2 receptors consist of an IL-4Rα subunit bound to a different subunit known as IL-13Rα1 and these type 2 receptors have the ability to bind both IL-4 and IL-13, two cytokines with closely related biological functions. IL-4 has a compact, globular fold, stabilised by 3 disulphide bonds, one half of the structure is dominated by a 4 alpha-helix bundle with a left-handed twist. The helices are anti-parallel, with 2 overhand connections, which fall into a 2-stranded anti-parallel beta-sheet and this cytokine was co-discovered by Maureen Howard and William E. Paul as well as by Ellen Vitetta and her research group in 1982. The nucleotide sequence for human IL-4 was isolated four years later confirming its similarity to a protein called B-cell stimulatory factor-1. IL-4 also has shown to drive mitogenesis, dedifferentiation. IL-4, along with other Th2 cytokines, is involved in the inflammation observed in the lungs of patients with allergic asthma
31.
Phagocytosis
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In cell biology, phagocytosis is the process by which a cell—often a phagocyte or a protist—engulfs a solid particle to form an internal compartment known as a phagosome. It is distinct from other forms of endocytosis like pinocytosis that involves the internalization of extracellular liquids, phagocytosis is involved in the acquisition of nutrients for some cells. In an organisms immune system, phagocytosis is a mechanism used to remove pathogens. For example, when a macrophage ingests a pathogenic microorganism, the pathogen becomes trapped in a phagosome which then fuses with a lysosome to form a phagolysosome, within the phagolysosome, enzymes and toxic peroxides digest the pathogen. Bacteria, dead cells, and small mineral particles are all examples of objects that may be phagocytized. The process has triggered the name Phagocytes for the 1st line of defence in the immune system, phagocytosis was first noted by Canadian physician William Osler, and later studied and named by Élie Metchnikoff. Phagocytosis in mammalian cells is activated by attachment to pathogen-associated molecular patterns. Opsonins such as C3b and antibodies can act as attachment sites, engulfment of material is facilitated by the actin-myosin contractile system. The phagosome of ingested material is fused with the lysosome, forming a phagolysosome. Degradation can be oxygen-dependent or oxygen-independent, oxygen-dependent degradation depends on NADPH and the production of reactive oxygen species. Hydrogen peroxide and myeloperoxidase activate a system, which leads to the creation of hypochlorite. Oxygen-independent degradation depends on the release of granules, containing proteolytic enzymes such as defensins, lysozyme, other antimicrobial peptides are present in these granules, including lactoferrin, which sequesters iron to provide unfavourable growth conditions for bacteria. It is possible for other than dedicated phagocytes to engage in phagocytosis. Some white blood cells in human immune system perform phagocytosis by gulping in some pathogenic, following apoptosis, the dying cells need to be taken up into the surrounding tissues by macrophages in a process called efferocytosis. Defects in apoptotic cell clearance is usually associated with impaired phagocytosis of macrophages, in many protists, phagocytosis is used as a means of feeding, providing part or all of their nourishment. This is called phagotrophic nutrition, distinguished from osmotrophic nutrition which takes place by absorption, in some, such as amoeba, phagocytosis takes place by surrounding the target object with pseudopods, as in animal phagocytes. In humans, entamoeba histolytica can phagocytose red blood cells, Entamoeba histolytica is an anaerobic parasitic protozoan, part of the genus Entamoeba. Predominantly infecting humans and other primates, E. histolytica is estimated to infect about 50 million people worldwide
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Opsonin
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An opsonin is any molecule that enhances phagocytosis by marking an antigen for an immune response or marking dead cells for recycling. Opson in ancient Greece referred to the delicious side-dish of any meal, versus the sitos, with the antigen coated in opsonins, binding to immune cells is greatly enhanced. Opsonization also mediates phagocytosis via signal cascades from cell surface receptors, Opsonins aid the immune system in a number of ways. All cell membranes have negative charges which makes it difficult for two cells to come close together, when opsonins bind to their targets they boost the kinetics of phagocytosis by favoring interaction between the opsonin and cell surface receptors on immune cells. This overrides the negative charges from cell membranes and this principle holds true for clearance of pathogens as well as dead or dying self cells. Opsonin molecules include, Antibodies are part of the immune response and are generated by B cells in response to antigen exposure. The Fab region of the antibody binds to the antigen, whereas the Fc region of the antibody binds to an Fc receptor on the phagocyte, the antigen-antibody complex can also activate complement through the classical complement pathway. Phagocytic cells do not have an Fc receptor for immunoglobulin M, however, IgM is extremely efficient at activating complement and is, therefore, considered an opsonin. IgG antibodies are also capable of binding immune effector cells via their Fc domain and this process, called antibody-dependent cellular cytotoxicity, can cause inflammation of surrounding tissues and damage to healthy cells. The complement system is a part of the immune response. C3b, C4b, and C1q are important complement molecules that serve as opsonins, as a part of the alternative complement pathway, the spontaneous activation of a complement cascade converts C3 to C3b, a component that can serve as an opsonin when bound to an antigens surface. Antibodies can also activate complement via the pathway, resulting in deposition of C3b. After C3b has bound to the surface of an antigen, it can be recognized by phagocyte receptors that signal for phagocytosis, complement receptor 1 is expressed on all phagocytes and recognizes a number of complement opsonins, including C3b and C4b which are both parts of C3-convertase. C1q, a member of the C1 complex, is able to interact with the Fc region of antibodies, pentraxins, collectins, and ficolins are all circulating proteins that are capable of serving as opsonins. They are secreted Pattern recognition receptors and these molecules coat the microbes as opsonins and enhance neutrophil reactivity against them through a number of mechanisms. Apoptosis is related to low tissue inflammation, a number of opsonins play a role in marking apoptotic cells for phagocytosis without a pro-inflammatory response. Members of the family can bind to apoptotic cell membrane components like phosphatidylcholine and phosphatidylethanolamine. IgM antibodies also bind to PC, collectin molecules such as mannose-binding lectin, surfactant protein A, and SP-D interact with unknown ligands on apoptotic cell membranes
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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
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Complement system
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It is part of the innate immune system, which is not adaptable and does not change over the course of an individuals lifetime. It can be recruited and brought into action by the immune system. The complement system consists of a number of proteins found in the blood, in general synthesized by the liver. When stimulated by one of several triggers, proteases in the system cleave specific proteins to release cytokines, over 30 proteins and protein fragments make up the complement system, including serum proteins, serosal proteins, and cell membrane receptors. They account for about 10% of the fraction of blood serum. Three biochemical pathways activate the complement system, the complement pathway, the alternative complement pathway. In 1888, George Nuttall found that blood serum had mild killing activity against the bacterium that causes anthrax. The killing activity disappeared when he heated the blood, in 1891, Hans Ernst August Buchner, noting the same property of blood in his experiments, named the killing property alexin, which means to ward off in Greek. By 1884, several laboratories had demonstrated that serum from guinea pigs that had recovered from cholera killed the cholera bacterium in vitro, heating the serum destroyed its killing activity. Nevertheless, the serum, when injected into guinea pigs exposed to the cholera bacteria. In 1899, Paul Ehrlich renamed the heat-sensitive component complement, Ehrlich introduced the term complement as part of his larger theory of the immune system. According to this theory, the system consists of cells that have specific receptors on their surface to recognize antigens. Upon immunisation with an antigen, more of these receptors are formed, Ehrlich, therefore, named this heat-labile component complement, because it is something in the blood that complements the cells of the immune system. Ehrlich believed that each antigen-specific amboceptor has its own specific complement, in the early 20th century, this controversy was resolved when it became understood that complement can act in combination with specific antibodies, or on its own in a non-specific way. Complement triggers the immune functions, Phagocytosis – by opsonizing antigens. But significant amounts are produced by tissue macrophages, blood monocytes. The three pathways of activation all generate homologous variants of the protease C3-convertase, the mannose-binding lectin pathway can be activated by C3 hydrolysis or antigens without the presence of antibodies. In all three pathways, C3-convertase cleaves and activates component C3, creating C3a and C3b, and causes a cascade of further cleavage, C3b binds to the surface of pathogens, leading to greater internalization by phagocytic cells by opsonization
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Antibody-dependent cell-mediated cytotoxicity
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In humans, ADCC is usually mediated by IgG. It is one of the mechanisms through which antibodies, as part of the immune response, can act to limit. Classical antibody-dependent cell-mediated cytotoxicity is mediated by natural killer cells, but macrophages, for example, eosinophils can kill certain parasitic worms known as helminths through ADCC mediated by IgE. ADCC is part of the immune response due to its dependence on a prior antibody response. The typical ADCC involves activation of NK cells by antibodies, a NK cell expresses Fc receptors, mostly CD16. These receptors recognize, and bind to, the Fc portion of an antibody, such as IgG, the most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII. Antibodies can then bind to these viral proteins, furthermore, NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface, indicating a non-self cell. This is because, generally, all nucleated cells of the body contain MHC I, large parasites like helminths are too big to be engulfed and killed by phagocytosis. They also have a structure or integument that is resistant to attack by substances released by neutrophils. After IgE coat these parasites, the Fc receptor of an eosinophil will then recognize IgE, subsequently, interaction between FceRI and the Fc portion of helminth-bound IgE signals the eosinophil to degranulate. Several laboratory methods exist for determining the efficacy of antibodies or effector cells in eliciting ADCC, among these methods include chromium-51 release assay, europium release assay, and sulfur-35 release assay. Usually, a target cell line expressing a certain surface-exposed antigen is incubated with antibody specific for that antigen. After washing, effector cells expressing Fc receptor CD16 are co-incubated with the target cells. Target cell lysis is subsequently measured by release of intracellular label by a counter or spectrophotometry. A common challenge faced by ADCC assays is high background signaling due to cellular leakiness, the coupled bioluminescent method aCella TOX is now in widespread use for ADCC and other cytotoxicity assessments. Since this technique measures the release of enzymes present in the target cells, no labeling step is required. Experiments in mice indicate that ADCC is an important mechanism of action of therapeutic antibodies, including trastuzumab and rituximab. In the clinic the FcgRIII 158V/F polymorphism interfere with the ability to generate ADCC responses in vitro during trastuzumab treatment, pier GB, Lyczak JB, Wetzler LM
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Chemokine
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Chemokines are a family of small cytokines, or signaling proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells, cytokine proteins are classified as chemokines according to behavior and structural characteristics. Chemokines are found in all vertebrates, some viruses and some bacteria, Chemokines have been classified into four main subfamilies, CXC, CC, CX3C and XC. The major role of chemokines is to act as a chemoattractant to guide the migration of cells, cells that are attracted by chemokines follow a signal of increasing chemokine concentration towards the source of the chemokine. These are known as homeostatic chemokines and are produced and secreted without any need to stimulate their source cell, some chemokines have roles in development, they promote angiogenesis, or guide cells to tissues that provide specific signals critical for cellular maturation. Their release is stimulated by pro-inflammatory cytokines such as interleukin 1. Inflammatory chemokines function mainly as chemoattractants for leukocytes, recruiting monocytes, neutrophils, certain inflammatory chemokines activate cells to initiate an immune response or promote wound healing. They are released by different cell types and serve to guide cells of both innate immune system and adaptive immune system. Chemokines are functionally divided into two groups, Homeostatic, are produced in certain tissues and are responsible for basal leukocyte migration. These include, CCL14, CCL19, CCL20, CCL21, CCL25, CCL27, CXCL12 and this classification is not strict, for example, CCL20 can act also as pro-inflammatory chemokine. Inflammatory, these are formed under conditions and actively participate in the inflammatory response attracting immune cells to the site of inflammation. Examples are, CXCL-8, CCL2, CCL3, CCL4, CCL5, CCL11, the main function of chemokines is to manage the migration of leukocytes in the respective anatomical locations in inflammatory and homeostatic processes. Basal, homeostatic chemokines are produced in the thymus and lymphoid tissues. Their homeostatic function in homing is best exemplified by the chemokines CCL19 and CCL21, using these ligands is possible routing antigen-presenting cells to lymph nodes during the adaptive immune response. Among other homeostatic chemokine receptors include, CCR9, CCR10, and CXCR5, CCR9 supports the migration of leukocytes into the intestine, CCR10 to the skin and CXCR5 supports the migration of B-cell to follicles of lymph nodes. As well CXCL12 constitutively produced in the bone marrow promotes proliferation of progenitor B cells in the bone marrow microenvironment, inflammatory, inflammatory chemokines are produced in high concentrations during infection or injury and determine the migration of inflammatory leukocytes into the damaged area. Typical inflammatory chemokines include, CCL2, CCL3 and CCL5, CXCL1, CXCL2, a typical example is CXCL-8, which chemoatractants for neutrophils. In contrast to the chemokine receptors, there is significantly promiscuous binding receptor
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Monocyte chemotactic protein-1
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For the ICAO airport code see Candle Lake Airpark, for the diradical compound see Dichlorocarbene. The chemokine ligand 2 is also referred to as monocyte chemoattractant protein 1, CCL2 is a small cytokine that belongs to the CC chemokine family. CCL2 recruits monocytes, memory T cells, and dendritic cells to the sites of inflammation produced by either injury or infection. In the human genome, CCL2 and many other CC chemokines are located on chromosome 17, the gene span is 1,927 bases and the CCL2 gene resides on the Watson strand. The CCL2 gene has three exons and two introns, the CCL2 protein precursor contains a signal peptide of 23 amino acids. In turn, the mature CCL2 is 76 amino acids long, the CCL2 predicted weight is 11.025 kiloDaltons. The gene homologous to CCL2 in the mouse is Sig-je, in humans, the levels of CCL2 can vary considerably. CCL2 is anchored in the membrane of endothelial cells by glycosaminoglycan side chains of proteoglycans. CCL2 is primarily secreted by monocytes, macrophages and dendritic cells, platelet derived growth factor is a major inducer of CCL2 gene. To become activated CCL2 protein has to be cleaved by metalloproteinase MMP-12, CCR2 and CCR4 are two cell surface receptors that bind CCL2. CCL2 exhibits a chemotactic activity for monocytes and basophils, however, it does not attract neutrophils or eosinophils. After deletion of the N-terminal residue, CCL2 loses its attractivity for basophils, basophils and mast cells that are treated with CCL2 release their granules to the intercellular space. This effect can be potentiated by a pre-treatment with IL-3 or even by other cytokines. CCL2 augments monocyte anti-tumor activity and it is essential for formation of granulomas, CCL2 can be found at the sites of tooth eruption and bone degradation. In the bone, CCL2 is expressed by osteoclasts and osteoblasts. In the human osteoclasts, CCL2 and RANTES and it is proposed that CCL2 and RANTES act as autocrine loop in human osteoclast differentiation. The CCL2 chemokine is also expressed by neurons, astrocytes and microglia, CCL2 is implicated in pathogeneses of several diseases characterized by monocytic infiltrates, such as psoriasis, rheumatoid arthritis and atherosclerosis. Administration of anti-CCL2 antibodies in a model of glomerulonephritis reduces infiltration of macrophages and T cells, reduces crescent formation, as well as scarring and renal impairment
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CCL7
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Chemokine ligand 7 is a small cytokine known as a chemokine that was previously called monocyte-chemotactic protein 3. Due to CCL7 possessing two adjacent N-terminal cysteine residues in its protein, it is classified among the subfamily of chemokines known as CC chemokines. CCL7 specifically attracts monocytes, and regulates macrophage function and it is produced by certain tumor cell lines and by macrophages. This chemokine is located on chromosome 17 in humans, in a cluster containing many other CC chemokines and is most closely related to CCL2. CCL7 has been shown to interact with MMP2, human CCL7 genome location and CCL7 gene details page in the UCSC Genome Browser
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