Eosinophils, sometimes called eosinophiles or, less acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along with mast cells and basophils, they control mechanisms associated with allergy and asthma, they are granulocytes that develop during hematopoiesis in the bone marrow before migrating into blood, after which they are terminally differentiated and do not multiply. These cells are eosinophilic or "acid-loving" due to their large acidophilic cytoplasmic granules, which show their affinity for acids by their affinity to coal tar dyes: Normally transparent, it is this affinity that causes them to appear brick-red after staining with eosin, a red dye, using the Romanowsky method; the staining is concentrated in small granules within the cellular cytoplasm, which contain many chemical mediators, such as eosinophil peroxidase, deoxyribonucleases, lipase and major basic protein.
These mediators are released by a process called degranulation following activation of the eosinophil, are toxic to both parasite and host tissues. In normal individuals, eosinophils make up about 1–3% of white blood cells, are about 12–17 micrometres in size with bilobed nuclei. While they are released into the bloodstream as neutrophils are, eosinophils reside in tissue, they are found in the medulla and the junction between the cortex and medulla of the thymus, and, in the lower gastrointestinal tract, uterus and lymph nodes, but not in the lungs, esophagus, or some other internal organs under normal conditions. The presence of eosinophils in these latter organs is associated with disease. For instance, patients with eosinophilic asthma have high levels of eosinophils that lead to inflammation and tissue damage, making it more difficult for patients to breathe. Eosinophils persist in the circulation for 8–12 hours, can survive in tissue for an additional 8–12 days in the absence of stimulation.
Pioneering work in the 1980s elucidated that eosinophils were unique granulocytes, having the capacity to survive for extended periods of time after their maturation as demonstrated by ex-vivo culture experiments. TH2 and ILC2 cells both express the transcription factor GATA-3 which promotes the production of TH2 cytokines, including the interleukins. IL-5 controls the development of eosinophils in the bone marrow, as they differentiate from myeloid precursor cells, their lineage fate is determined by transcription factors, including GATA and C/EBP. Eosinophils produce and store many secondary granule proteins prior to their exit from the bone marrow. After maturation, eosinophils circulate in blood and migrate to inflammatory sites in tissues, or to sites of helminth infection in response to chemokines like CCL11, CCL24, CCL5, 5-hydroxyicosatetraenoic acid and 5-oxo-eicosatetraenoic acid, certain leukotrienes like leukotriene B4 and MCP1/4. Interleukin-13, another TH2 cytokine, primes eosinophilic exit from the bone marrow by lining vessel walls with adhesion molecules such as VCAM-1 and ICAM-1.
When eosinophils are activated, they undergo cytolysis, where the breaking of the cell releases eosinophilic granules found in extracellular DNA traps. High concentrations of these DNA traps are known to cause cellular damage, as the granules they contain are responsible for the ligand-induced secretion of eosinophilic toxins which cause structural damage. There is evidence to suggest that eosinophil granule protein expression is regulated by the non-coding RNA EGOT. Following activation, eosinophils effector functions include production of the following: Cationic granule proteins and their release by degranulation Reactive oxygen species such as hypobromite and peroxide Lipid mediators like the eicosanoids from the leukotriene and prostaglandin families Enzymes, such as elastase Growth factors such as TGF beta, VEGF, PDGF Cytokines such as IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-13, TNF alphaThere are eosinophils that play a role in fighting viral infections, evident from the abundance of RNases they contain within their granules, in fibrin removal during inflammation.
Eosinophils, along with basophils and mast cells, are important mediators of allergic responses and asthma pathogenesis and are associated with disease severity. They fight helminth colonization and may be elevated in the presence of certain parasites. Eosinophils are involved in many other biological processes, including postpubertal mammary gland development, oestrus cycling, allograft rejection and neoplasia, they have been implicated in antigen presentation to T cells. Eosinophils are responsible for tissue damage and inflammation including asthma. High levels of interleukin-5 has been observed to up regulate the expression of adhesion molecules, which facilitate the adhesion of eosinophils to endothelial cells, thereby causing inflammation and tissue damage. An accumulation of eosinophils in the nasal mucosa is considered a major diagnostic criterion for allergic rhinitis. Following activation by an immune stimulus, eosinophils degranulate to release an array of cytotoxic granule cationic proteins that are capable of inducing tissue damage and dysfunction.
These include: major basic protein eosinophil cationic protein eosinophil peroxidase eosinophil-derived neurotoxin Major basic protein, eosinophil peroxidase, eosinophil cationic protein are toxic to many tissues. Eosinophil cationic protein and eosinophil-derived neurotoxin are ribonucleases w
Necrosis is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma which result in the unregulated digestion of cell components. In contrast, apoptosis is a occurring programmed and targeted cause of cellular death. While apoptosis provides beneficial effects to the organism, necrosis is always detrimental and can be fatal. Cellular death due to necrosis does not follow the apoptotic signal transduction pathway, but rather various receptors are activated, result in the loss of cell membrane integrity and an uncontrolled release of products of cell death into the extracellular space; this initiates in the surrounding tissue an inflammatory response which attracts leukocytes and nearby phagocytes which eliminate the dead cells by phagocytosis. However, microbial damaging substances released by leukocytes would create collateral damage to surrounding tissues.
This excess collateral damage inhibits the healing process. Thus, untreated necrosis results in a build-up of decomposing dead tissue and cell debris at or near the site of the cell death. A classic example is gangrene. For this reason, it is necessary to remove necrotic tissue surgically, a procedure known as debridement. Structural signs that indicate irreversible cell injury and the progression of necrosis include dense clumping and progressive disruption of genetic material, disruption to membranes of cells and organelles. There are six distinctive morphological patterns of necrosis: Coagulative necrosis is characterized by the formation of a gelatinous substance in dead tissues in which the architecture of the tissue is maintained, can be observed by light microscopy. Coagulation occurs as a result of protein denaturation, causing albumin to transform into a firm and opaque state; this pattern of necrosis is seen in hypoxic environments, such as infarction. Coagulative necrosis occurs in tissues such as the kidney and adrenal glands.
Severe ischemia most causes necrosis of this form. Liquefactive necrosis, in contrast to coagulative necrosis, is characterized by the digestion of dead cells to form a viscous liquid mass; this is typical of bacterial, or sometimes fungal, infections because of their ability to stimulate an inflammatory response. The necrotic liquid mass is creamy yellow due to the presence of dead leukocytes and is known as pus. Hypoxic infarcts in the brain presents as this type of necrosis, because the brain contains little connective tissue but high amounts of digestive enzymes and lipids, cells therefore can be digested by their own enzymes. Gangrenous necrosis can be considered a type of coagulative necrosis that resembles mummified tissue, it is characteristic of ischemia of the gastrointestinal tracts. If superimposed infection of dead tissues occurs liquefactive necrosis ensues Caseous necrosis can be considered a combination of coagulative and liquefactive necrosis caused by mycobacteria and some foreign substances.
The necrotic tissue appears as friable, like clumped cheese. Dead cells disintegrate but are not digested, leaving granular particles. Microscopic examination shows amorphous granular debris enclosed within a distinctive inflammatory border. Granuloma has this characteristic. Fat necrosis is specialized necrosis of fat tissue, resulting from the action of activated lipases on fatty tissues such as the pancreas. In the pancreas it leads to acute pancreatitis, a condition where the pancreatic enzymes leak out into the peritoneal cavity, liquefy the membrane by splitting the triglyceride esters into fatty acids through fat saponification. Calcium, magnesium or sodium may bind to these lesions to produce a chalky-white substance; the calcium deposits are microscopically distinctive and may be large enough to be visible on radiographic examinations. To the naked eye, calcium deposits appear as gritty white flecks. Fibrinoid necrosis is a special form of necrosis caused by immune-mediated vascular damage.
It is marked by complexes of antigen and antibodies, sometimes referred to as "immune complexes" deposited within arterial walls together with fibrin. There are very specific forms of necrosis such as gangrene, gummatous necrosis and hemorrhagic necrosis; some spider bites may lead to necrosis. In the United States, only spider bites from the brown recluse spider reliably progress to necrosis. In other countries, spiders of the same genus, such as the Chilean recluse in South America, are known to cause necrosis. Claims that yellow sac spiders and hobo spiders possess necrotic venom have not been substantiated. In blind mole rats, the process of necrosis replaces the role of the systematic apoptosis used in many organisms. Low oxygen conditions, such as those common in blind mole rats' burrows cause cells to undergo apoptosis. In adaptation to higher tendency of cell death, blind mole rats evolved a mutation in the tumor suppressor protein p53 to prevent cells from undergoing apoptosis. Human cancer patients have similar mutations, blind mole rats were thought to be more susceptible to cancer because their cells cannot undergo apoptosis.
However, after a specific amount of time (within 3 days according to a study conducted at the University of
Neutrophils are the most abundant type of granulocytes and the most abundant type of white blood cells in most mammals. They form an essential part of the innate immune system, their functions vary in different animals. They are formed from stem cells in the bone marrow and differentiated into subpopulations of neutrophil-killers and neutrophil-cagers, they are short-lived and motile, or mobile, as they can enter parts of tissue where other cells/molecules cannot. Neutrophils may be banded neutrophils, they form part of the polymorphonuclear cells family together with eosinophils. The name neutrophil derives from staining characteristics on hematoxylin and eosin histological or cytological preparations. Whereas basophilic white blood cells stain dark blue and eosinophilic white blood cells stain bright red, neutrophils stain a neutral pink. Neutrophils contain a nucleus divided into 2–5 lobes. Neutrophils are a type of phagocyte and are found in the bloodstream. During the beginning phase of inflammation as a result of bacterial infection, environmental exposure, some cancers, neutrophils are one of the first-responders of inflammatory cells to migrate towards the site of inflammation.
They migrate through the blood vessels through interstitial tissue, following chemical signals such as Interleukin-8, C5a, fMLP, Leukotriene B4 and H2O2 in a process called chemotaxis. They are the predominant cells in pus, accounting for its whitish/yellowish appearance. Neutrophils are recruited to the site of injury within minutes following trauma and are the hallmark of acute inflammation; when adhered to a surface, neutrophil granulocytes have an average diameter of 12–15 micrometers in peripheral blood smears. In suspension, human neutrophils have an average diameter of 8.85 µm. With the eosinophil and the basophil, they form the class of polymorphonuclear cells, named for the nucleus' multilobulated shape; the nucleus has the separate lobes connected by chromatin. The nucleolus disappears as the neutrophil matures, something that happens in only a few other types of nucleated cells. In the cytoplasm, the Golgi apparatus is small and ribosomes are sparse, the rough endoplasmic reticulum is absent.
The cytoplasm contains about 200 granules, of which a third are azurophilic. Neutrophils will show increasing segmentation. A normal neutrophil should have 3–5 segments. Hypersegmentation occurs in some disorders, most notably vitamin B12 deficiency; this is noted in a manual review of the blood smear and is positive when most or all of the neutrophils have 5 or more segments. Neutrophils are the most abundant white blood cells in humans; the stated normal range for human blood counts varies between laboratories, but a neutrophil count of 2.5–7.5 x 109/L is a standard normal range. People of African and Middle Eastern descent may have lower counts. A report may divide neutrophils into segmented bands; when circulating in the bloodstream and inactivated, neutrophils are spherical. Once activated, they change shape and become more amorphous or amoeba-like and can extend pseudopods as they hunt for antigens. Neutrophils have a preference to engulf refined carbohydrates over bacteria. In 1973 Sanchez et al. found that the neutrophil phagocytic capacity to engulf bacteria is affected when simple sugars are digested, that fasting strengthens the neutrophils' phagocytic capacity to engulf bacteria.
However, the digestion of normal starches has no effect. It was concluded that the function, not the number, of phagocytes in engulfing bacteria was altered by the ingestion of sugars. In 2007 researchers at the Whitehead Institute of Biomedical Research found that given a selection of sugars, neutrophils engulf some types of sugar preferentially; the average lifespan of inactivated human neutrophils in the circulation has been reported by different approaches to be between 5 and 90 hours. Upon activation, they marginate and undergo selectin-dependent capture followed by integrin-dependent adhesion in most cases, after which they migrate into tissues, where they survive for 1–2 days. Neutrophils are much more numerous than the longer-lived monocyte/macrophage phagocytes. A pathogen is to first encounter a neutrophil; some experts hypothesize. The short lifetime of neutrophils minimizes propagation of those pathogens that parasitize phagocytes because the more time such parasites spend outside a host cell, the more they will be destroyed by some component of the body's defenses.
Because neutrophil antimicrobial products can damage host tissues, their short life limits damage to the host during inflammation. Neutrophils will be removed after phagocytosis of pathogens by macrophages. PECAM-1 and phosphatidylserine on the cell surface are involved in this process. Neutrophils undergo a process called chemotaxis via amoeboid movement, which allows them to migrate toward sites of infection or inflammation. Cell surface receptors allow neutrophils to detect chemical gr
Bacteria are a type of biological cell. They constitute a large domain of prokaryotic microorganisms. A few micrometres in length, bacteria have a number of shapes, ranging from spheres to rods and spirals. Bacteria were among the first life forms to appear on Earth, are present in most of its habitats. Bacteria inhabit soil, acidic hot springs, radioactive waste, the deep portions of Earth's crust. Bacteria live in symbiotic and parasitic relationships with plants and animals. Most bacteria have not been characterised, only about half of the bacterial phyla have species that can be grown in the laboratory; the study of bacteria is known as a branch of microbiology. There are 40 million bacterial cells in a gram of soil and a million bacterial cells in a millilitre of fresh water. There are 5×1030 bacteria on Earth, forming a biomass which exceeds that of all plants and animals. Bacteria are vital in many stages of the nutrient cycle by recycling nutrients such as the fixation of nitrogen from the atmosphere.
The nutrient cycle includes the decomposition of dead bodies. In the biological communities surrounding hydrothermal vents and cold seeps, extremophile bacteria provide the nutrients needed to sustain life by converting dissolved compounds, such as hydrogen sulphide and methane, to energy. Data reported by researchers in October 2012 and published in March 2013 suggested that bacteria thrive in the Mariana Trench, with a depth of up to 11 kilometres, is the deepest known part of the oceans. Other researchers reported related studies that microbes thrive inside rocks up to 580 metres below the sea floor under 2.6 kilometres of ocean off the coast of the northwestern United States. According to one of the researchers, "You can find microbes everywhere—they're adaptable to conditions, survive wherever they are."The famous notion that bacterial cells in the human body outnumber human cells by a factor of 10:1 has been debunked. There are 39 trillion bacterial cells in the human microbiota as personified by a "reference" 70 kg male 170 cm tall, whereas there are 30 trillion human cells in the body.
This means that although they do have the upper hand in actual numbers, it is only by 30%, not 900%. The largest number exist in the gut flora, a large number on the skin; the vast majority of the bacteria in the body are rendered harmless by the protective effects of the immune system, though many are beneficial in the gut flora. However several species of bacteria are pathogenic and cause infectious diseases, including cholera, anthrax and bubonic plague; the most common fatal bacterial diseases are respiratory infections, with tuberculosis alone killing about 2 million people per year in sub-Saharan Africa. In developed countries, antibiotics are used to treat bacterial infections and are used in farming, making antibiotic resistance a growing problem. In industry, bacteria are important in sewage treatment and the breakdown of oil spills, the production of cheese and yogurt through fermentation, the recovery of gold, palladium and other metals in the mining sector, as well as in biotechnology, the manufacture of antibiotics and other chemicals.
Once regarded as plants constituting the class Schizomycetes, bacteria are now classified as prokaryotes. Unlike cells of animals and other eukaryotes, bacterial cells do not contain a nucleus and harbour membrane-bound organelles. Although the term bacteria traditionally included all prokaryotes, the scientific classification changed after the discovery in the 1990s that prokaryotes consist of two different groups of organisms that evolved from an ancient common ancestor; these evolutionary domains are called Archaea. The word bacteria is the plural of the New Latin bacterium, the latinisation of the Greek βακτήριον, the diminutive of βακτηρία, meaning "staff, cane", because the first ones to be discovered were rod-shaped; the ancestors of modern bacteria were unicellular microorganisms that were the first forms of life to appear on Earth, about 4 billion years ago. For about 3 billion years, most organisms were microscopic, bacteria and archaea were the dominant forms of life. Although bacterial fossils exist, such as stromatolites, their lack of distinctive morphology prevents them from being used to examine the history of bacterial evolution, or to date the time of origin of a particular bacterial species.
However, gene sequences can be used to reconstruct the bacterial phylogeny, these studies indicate that bacteria diverged first from the archaeal/eukaryotic lineage. The most recent common ancestor of bacteria and archaea was a hyperthermophile that lived about 2.5 billion–3.2 billion years ago. Bacteria were involved in the second great evolutionary divergence, that of the archaea and eukaryotes. Here, eukaryotes resulted from the entering of ancient bacteria into endosymbiotic associations with the ancestors of eukaryotic cells, which were themselves related to the Archaea; this involved the engulfment by proto-eukaryotic cells of alphaproteobacterial symbionts to form either mitochondria or hydrogenosomes, which are still found in all known Eukarya. Some eukaryotes that contained mitochondria engulfed cyanobacteria-like organisms, leading to the formation of chloroplasts in algae and plants; this is known as primary endosymbiosis. Bacteria display a wide diversity of sizes, called morphologies.
Bacterial cells are about one-tenth the size of eukaryotic cells
Histology microanatomy, is the branch of biology which studies the tissues of animals and plants using microscopy. It is studied using a light microscope or electron microscope, the specimen having been sectioned and mounted on a microscope slide. Histological studies may be conducted using tissue culture, where live animal cells are isolated and maintained in an artificial environment for various research projects; the ability to visualize or differentially identify microscopic structures is enhanced through the use of staining. Histology is one of the major preclinical subjects in medical school. Medical students are expected to be familiar with the morphological features and function of all cells and tissues of the human body from an early stage of their studies, so histology stretches over several semesters. Histopathology, the microscopic study of diseased tissue, is an important tool in anatomical pathology, since accurate diagnosis of cancer and other diseases requires histopathological examination of samples.
Trained physicians licensed pathologists, are the personnel who perform histopathological examination and provide diagnostic information based on their observations. The trained personnel who prepare histological specimens for examination are histotechnicians, histotechnologists, histology technicians, histology technologists, medical scientists, medical laboratory technicians, or biomedical scientists, their support workers, their field of study is called histotechnology. In the 17th century, Italian Marcello Malpighi invented one of the first microscopes for studying tiny biological entities. Malpighi analysed several parts of the organs of bats and other animals under the microscope. Malpighi, while studying the structure of the lung, noticed its membranous alveoli and the hair-like connections between veins and arteries, which he named capillaries, his discovery established how the oxygen enters the blood stream and serves the body. In the 19th century, histology was an academic discipline in its own right.
The French anatomist Bichat introduced the concept of tissue in anatomy in 1801, the term "histology" first appeared in a book of Karl Meyer in 1819. Bichat described twenty-one human tissues, which can be subsumed under the four categories accepted by histologists; the usage of illustrations in histology, deemed as useless by Bichat, was promoted by Jean Cruveilhier. During the 19th century, many fixation techniques were developed by Adolph Hannover, Franz Schulze and Max Schultze, Alexander Butlerov and Benedikt Stilling. In the early 1830, Purkynĕ invented a microtome with high precision. Mounting techniques were developed by Rudolf Heidenhain, Salomon Stricker, Andrew Pritchard and Edwin Klebs. Koelliker's laboratory developed haematoxylin staining, in 1870s, Vysockij introduced eosin as a double or counter staining; the 1906 Nobel Prize in Physiology or Medicine was awarded to histologists Camillo Golgi and Santiago Ramon y Cajal. They had conflicting interpretations of the neural structure of the brain based on differing interpretations of the same images.
Cajal won the prize for his correct theory, Golgi for the silver staining technique he invented to make it possible. There are four basic types of animal tissues: muscle tissue, nervous tissue, connective tissue, epithelial tissue. All tissue types are subtypes of these four basic tissue types. Epithelium: the lining of glands, bowel and some organs like the liver and kidney Endothelium: the lining of blood and lymphatic vessels Mesothelium: the lining of pleural and pericardial spaces Mesenchyme: the cells filling the spaces between the organs, including fat, bone and tendon cells Blood cells: the red and white blood cells, including those found in lymph nodes and spleen Neurons: any of the conducting cells of the nervous system Germ cells: reproductive cells Placenta: an organ characteristic of true mammals during pregnancy, joining mother and offspring, providing endocrine secretion and selective exchange of soluble, but not particulate, blood-borne substances through an apposition of uterine and trophoblastic vascularised parts Stem cells: cells with the ability to develop into different cell typesThe tissues from plants and microorganisms can be examined histologically.
Their structure is different from animal tissues. For plants, the study of their tissues is more called as plant anatomy, with the following main types: Dermal tissue Vascular tissue Ground tissue Meristematic tissue Chemical fixatives are used to preserve tissue from degradation, to maintain the structure of the cell and of sub-cellular components such as cell organelles; the most common fixative for light microscopy is 10% neutral buffered formalin. For electron microscopy, the most used fixative is glutaraldehyde as a 2.5% solution in phosphate buffered saline. These fixatives preserve tissues or cells by irreversibly cross-linking proteins; the main action of these aldehyde fixatives is to cross-link amino groups in proteins through the formation of methylene bridges, in the case of formaldehyde, or by C5H10 cross-links in the case of glutaraldehyde. This process, while preserving the structural integrity of the cells and tissue can damage the biological functionality of proteins enzymes, and
Inflammation is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, is a protective response involving immune cells, blood vessels, molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, initiate tissue repair; the five classical signs of inflammation are heat, redness and loss of function. Inflammation is a generic response, therefore it is considered as a mechanism of innate immunity, as compared to adaptive immunity, specific for each pathogen. Too little inflammation could lead to progressive tissue destruction by the harmful stimulus and compromise the survival of the organism. In contrast, chronic inflammation may lead to a host of diseases, such as hay fever, atherosclerosis, rheumatoid arthritis, cancer. Inflammation is therefore closely regulated by the body. Inflammation can be classified as either chronic.
Acute inflammation is the initial response of the body to harmful stimuli and is achieved by the increased movement of plasma and leukocytes from the blood into the injured tissues. A series of biochemical events propagates and matures the inflammatory response, involving the local vascular system, the immune system, various cells within the injured tissue. Prolonged inflammation, known as chronic inflammation, leads to a progressive shift in the type of cells present at the site of inflammation, such as mononuclear cells, is characterized by simultaneous destruction and healing of the tissue from the inflammatory process. Inflammation is not a synonym for infection. Infection describes the interaction between the action of microbial invasion and the reaction of the body's inflammatory response—the two components are considered together when discussing an infection, the word is used to imply a microbial invasive cause for the observed inflammatory reaction. Inflammation on the other hand describes purely the body's immunovascular response, whatever the cause may be.
But because of how the two are correlated, words ending in the suffix -itis are sometimes informally described as referring to infection. For example, the word urethritis means only "urethral inflammation", but clinical health care providers discuss urethritis as a urethral infection because urethral microbial invasion is the most common cause of urethritis, it is useful to differentiate inflammation and infection because there are typical situations in pathology and medical diagnosis where inflammation is not driven by microbial invasion – for example, trauma and autoimmune diseases including type III hypersensitivity. Conversely, there is pathology where microbial invasion does not cause the classic inflammatory response – for example, parasitosis or eosinophilia. Acute inflammation is a short-term process appearing within a few minutes or hours and begins to cease upon the removal of the injurious stimulus, it involves a coordinated and systemic mobilization response locally of various immune and neurological mediators of acute inflammation.
In a normal healthy response, it becomes activated, clears the pathogen and begins a repair process and ceases. It is characterized by five cardinal signs:An acronym that may be used to remember the key symptoms is "PRISH", for pain, immobility and heat; the traditional names for signs of inflammation come from Latin: Dolor Calor Rubor Tumor Functio laesa The first four were described by Celsus, while loss of function was added by Galen. However, the addition of this fifth sign has been ascribed to Thomas Sydenham and Virchow. Redness and heat are due to increased blood flow at body core temperature to the inflamed site. 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; the process of acute inflammation is initiated by resident immune cells present in the involved tissue resident macrophages, dendritic cells, Kupffer cells and mast cells. These cells possess surface receptors known as pattern recognition receptors, which recognize two subclasses of molecules: pathogen-associated molecular patterns and damage-associated molecular patterns.
PAMPs are compounds that are associated with various pathogens, but which are distinguishable from host molecules. DAMPs are compounds that are associated with host-related 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 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 bradykinin increase the sensitivity to pain. The mediator molecules alter the blood vessels to