Misplaced Pages

#618381

92-499: There are different categories of cancer cell, defined according to the cell type from which they originate. Cancer cells have distinguishing histological features visible under the microscope. The nucleus is often large and irregular, and the cytoplasm may also display abnormalities. The shape, size, protein composition, and texture of the nucleus are often altered in malignant cells . The nucleus may acquire grooves, folds or indentations, chromatin may aggregate or disperse, and

184-539: 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 induce their own phagocytosis by host macrophages in vivo, and inhibit digestion by lysosomal action, thereby using macrophages for their own replication and causing macrophage apoptosis. Macrophages can digest more than 100 bacteria before they finally die due to their own digestive compounds. When

276-796: A Russian Empire zoologist, in 1884. A majority of macrophages are stationed at strategic points where microbial invasion or accumulation of foreign particles is likely to occur. These cells together as a group are known as the mononuclear phagocyte system and were previously known as the reticuloendothelial system. Each type of macrophage, determined by its location, has a specific name: Investigations concerning Kupffer cells are hampered because in humans, Kupffer cells are only accessible for immunohistochemical analysis from biopsies or autopsies. From rats and mice, they are difficult to isolate, and after purification, only approximately 5 million cells can be obtained from one mouse. Macrophages can express paracrine functions within organs that are specific to

368-413: A description of this process). The neutrophils are at first attracted to a site, where they perform their function and die, before they or their neutrophil extracellular traps are phagocytized by the macrophages. When at the site, the first wave of neutrophils, after the process of aging and after the first 48 hours, stimulate the appearance of the macrophages whereby these macrophages will then ingest

460-419: A harder medium both as a support and to allow the cutting of thin tissue slices. In general, water must first be removed from tissues (dehydration) and replaced with a medium that either solidifies directly, or with an intermediary fluid (clearing) that is miscible with the embedding media. For light microscopy, paraffin wax is the most frequently used embedding material. Paraffin is immiscible with water,

552-559: A knife mounted in a microtome is used to cut tissue sections (typically between 5-15 micrometers thick) which are mounted on a glass microscope slide . For transmission electron microscopy (TEM), a diamond or glass knife mounted in an ultramicrotome is used to cut between 50 and 150 nanometer thick tissue sections. A limited number of manufacturers are recognized for their production of microtomes, including vibrating microtomes commonly referred to as vibratomes , primarily for research and clinical studies. Additionally, Leica Biosystems

644-400: A lack of these growth factors/anti-inflammatory cytokines and an overabundance of pro-inflammatory cytokines from M1 macrophages chronic wounds are unable to heal in a timely manner. Normally, after neutrophils eat debris/pathogens they perform apoptosis and are removed. At this point, inflammation is not needed and M1 undergoes a switch to M2 (anti-inflammatory). However, dysregulation occurs as

736-630: A large number of diseases. Some disorders, mostly rare, of ineffective phagocytosis and macrophage function have been described, for example. In their role as a phagocytic immune cell macrophages are responsible for engulfing pathogens to destroy them. Some pathogens subvert this process and instead live inside the macrophage. This provides an environment in which the pathogen is hidden from the immune system and allows it to replicate. Diseases with this type of behaviour include tuberculosis (caused by Mycobacterium tuberculosis ) and leishmaniasis (caused by Leishmania species). In order to minimize

828-649: A microscope. Other advanced techniques, such as nonradioactive in situ hybridization, can be combined with immunochemistry to identify specific DNA or RNA molecules with fluorescent probes or tags that can be used for immunofluorescence and enzyme-linked fluorescence amplification (especially alkaline phosphatase and tyramide signal amplification). Fluorescence microscopy and confocal microscopy are used to detect fluorescent signals with good intracellular detail. For electron microscopy heavy metals are typically used to stain tissue sections. Uranyl acetate and lead citrate are commonly used to impart contrast to tissue in

920-540: A mixture of wax and oil; and Andrew Pritchard (1804–1884) who, in 1832, used a gum/ isinglass mixture. In the same year, Canada balsam appeared on the scene, and in 1869 Edwin Klebs (1834–1913) reported that he had for some years embedded his specimens in paraffin. The 1906 Nobel Prize in Physiology or Medicine was awarded to histologists Camillo Golgi and Santiago Ramon y Cajal . They had conflicting interpretations of

1012-448: A number of factors such as growth factors and other cytokines, especially during the third and fourth post-wound days. These factors attract cells involved in the proliferation stage of healing to the area. Macrophages may also restrain the contraction phase. Macrophages are stimulated by the low oxygen content of their surroundings to produce factors that induce and speed angiogenesis and they also stimulate cells that re-epithelialize

SECTION 10

#1732884239619

1104-869: A pathogen invades, tissue resident macrophages are among the first cells to respond. Two of the main roles of the tissue resident macrophages are to phagocytose incoming antigen and to secrete proinflammatory cytokines that induce inflammation and recruit other immune cells to the site. Macrophages can internalize antigens through receptor-mediated phagocytosis. Macrophages have a wide variety of pattern recognition receptors (PRRs) that can recognize microbe-associated molecular patterns (MAMPs) from pathogens. Many PRRs, such as toll-like receptors (TLRs), scavenger receptors (SRs), C-type lectin receptors, among others, recognize pathogens for phagocytosis. Macrophages can also recognize pathogens for phagocytosis indirectly through opsonins , which are molecules that attach to pathogens and mark them for phagocytosis. Opsonins can cause

1196-463: A pro-inflammatory response that in return produce pro-inflammatory cytokines like Interleukin-6 and TNF. Unlike M1 macrophages, M2 macrophages secrete an anti-inflammatory response via the addition of Interleukin-4 or Interleukin-13. They also play a role in wound healing and are needed for revascularization and reepithelialization. M2 macrophages are divided into four major types based on their roles: M2a, M2b, M2c, and M2d. How M2 phenotypes are determined

1288-805: A role in naïve or memory CD8 T cell activation is still unclear. Macrophages have been shown to secrete cytokines BAFF and APRIL, which are important for plasma cell isotype switching. APRIL and IL-6 secreted by macrophage precursors in the bone marrow help maintain survival of plasma cells homed to the bone marrow. There are several activated forms of macrophages. In spite of a spectrum of ways to activate macrophages, there are two main groups designated M1 and M2 . M1 macrophages: as mentioned earlier (previously referred to as classically activated macrophages), M1 "killer" macrophages are activated by LPS and IFN-gamma , and secrete high levels of IL-12 and low levels of IL-10 . M1 macrophages have pro-inflammatory, bactericidal, and phagocytic functions. In contrast,

1380-462: A role. Stem cell research suggests that excess SP2 protein may turn stem cells into cancer cells. However, a lack of particular co-stimulated molecules that aid in the way antigens react with lymphocytes can impair the natural killer cells' function, ultimately leading to cancer. When a cell is deficient in the capacity to repair DNA damages , such damages tend to be retained within the cell at an increased level. These damages, upon replication of

1472-410: A scarring response. As described above, macrophages play a key role in removing dying or dead cells and cellular debris. Erythrocytes have a lifespan on average of 120 days and so are constantly being destroyed by macrophages in the spleen and liver. Macrophages will also engulf macromolecules , and so play a key role in the pharmacokinetics of parenteral irons . The iron that is released from

1564-461: A specific chemical is the Perls' Prussian blue reaction, used to demonstrate iron deposits in diseases like hemochromatosis . The Nissl method for Nissl substance and Golgi's method (and related silver stains ) are useful in identifying neurons are other examples of more specific stains. In historadiography , a slide (sometimes stained histochemically) is X-rayed. More commonly, autoradiography

1656-429: A stronger adhesion between the macrophage and pathogen during phagocytosis, hence opsonins tend to enhance macrophages’ phagocytic activity. Both complement proteins and antibodies can bind to antigens and opsonize them. Macrophages have complement receptor 1 (CR1) and 3 (CR3) that recognize pathogen-bound complement proteins C3b and iC3b, respectively, as well as fragment crystallizable γ receptors (FcγRs) that recognize

1748-533: A type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells , microbes , cellular debris, and foreign substances, which do not have proteins that are specific to healthy body cells on their surface. This process is called phagocytosis , which acts to defend the host against infection and injury. Macrophages are found in essentially all tissues, where they patrol for potential pathogens by amoeboid movement . They take various forms (with various names) throughout

1840-416: Is miscible with the wax, finally melted paraffin wax is added to replace the xylene and infiltrate the tissue. In most histology, or histopathology laboratories the dehydration, clearing, and wax infiltration are carried out in tissue processors which automate this process. Once infiltrated in paraffin, tissues are oriented in molds which are filled with wax; once positioned, the wax is cooled, solidifying

1932-425: Is 10% neutral buffered formalin , or NBF (4% formaldehyde in phosphate buffered saline ). For electron microscopy, the most commonly used fixative is glutaraldehyde , usually as a 2.5% solution in phosphate buffered saline . Other fixatives used for electron microscopy are osmium tetroxide or uranyl acetate . The main action of these aldehyde fixatives is to cross-link amino groups in proteins through

SECTION 20

#1732884239619

2024-661: Is a broad spectrum of macrophage activation phenotypes, there are two major phenotypes that are commonly acknowledged. They are the classically activated macrophages, or M1 macrophages, and the alternatively activated macrophages, or M2 macrophages. M1 macrophages are proinflammatory, while M2 macrophages are mostly anti-inflammatory. T H 1 cells play an important role in classical macrophage activation as part of type 1 immune response against intracellular pathogens (such as intracellular bacteria ) that can survive and replicate inside host cells, especially those pathogens that replicate even after being phagocytosed by macrophages. After

2116-533: Is caused by mutation and epimutation of the genetic material of normal cells, which upsets the normal balance between proliferation and cell death. This results in uncontrolled cell division in the body. The uncontrolled and often rapid proliferation of cells can lead to benign or malignant tumours (cancer). Benign tumors do not spread to other parts of the body or invade other tissues. Malignant tumors can invade other organs, spread to distant locations ( metastasis ) and become life-threatening. More than one mutation

2208-750: Is classified as connective tissue, since the blood cells are suspended in an extracellular matrix , the plasma ). For plants, the study of their tissues falls under the field of plant anatomy , with the following four main types: Histopathology is the branch of histology that includes the microscopic identification and study of diseased tissue. It is an important part of anatomical pathology and surgical pathology , as accurate diagnosis of cancer and other diseases often requires histopathological examination of tissue samples. Trained physicians, frequently licensed pathologists , perform histopathological examination and provide diagnostic information based on their observations. The field of histology that includes

2300-442: Is known as classical macrophage activation, and the activated macrophages are known as classically activated macrophages, or M1 macrophages. The M1 macrophages in turn upregulate B7 molecules and antigen presentation through MHC class II molecules to provide signals that sustain T cell help. The activation of T H 1 and M1 macrophage is a positive feedback loop, with IFN-γ from T H 1 cells upregulating CD40 expression on macrophages;

2392-413: Is known for its production of products related to light microscopy in the context of research and clinical studies. Biological tissue has little inherent contrast in either the light or electron microscope. Staining is employed to give both contrast to the tissue as well as highlighting particular features of interest. When the stain is used to target a specific chemical component of the tissue (and not

2484-540: Is necessary for carcinogenesis. In fact, a series of several mutations to certain classes of genes is usually required before a normal cell will transform into a cancer cell. Damage to DNA can be caused by exposure to radiation, chemicals, and other environmental sources, but mutations also accumulate naturally over time through uncorrected errors in DNA transcription , making age another risk factor. Oncoviruses can cause certain types of cancer, and genetics are also known to play

2576-456: Is not muscle specific; they accumulate in numerous tissues during the healing process phase following injury. Macrophages are essential for wound healing . They replace polymorphonuclear neutrophils as the predominant cells in the wound by day two after injury. Attracted to the wound site by growth factors released by platelets and other cells, monocytes from the bloodstream enter the area through blood vessel walls. Numbers of monocytes in

2668-417: Is observed in several different kinds of cancer (see Misplaced Pages article O-6-methylguanine-DNA methyltransferase ). Although a DNA repair deficiency can predispose a cell lineage to develop cancer, increased (rather than decreased) expression of a repair capability may also emerge in the progression of cancer cell lineages, and this capability may be clinically important as reviewed by Lingg et al. For instance,

2760-481: Is possible using appropriate protocols. Selection is the choice of relevant tissue in cases where it is not necessary to put the entire original tissue mass through further processing. The remainder may remain fixed in case it needs to be examined at a later time. Trimming is the cutting of tissue samples in order to expose the relevant surfaces for later sectioning. It also creates tissue samples of appropriate size to fit into cassettes. Tissues are embedded in

2852-433: Is rebuilding. The first subpopulation has no direct benefit to repairing muscle, while the second non-phagocytic group does. It is thought that macrophages release soluble substances that influence the proliferation, differentiation, growth, repair, and regeneration of muscle, but at this time the factor that is produced to mediate these effects is unknown. It is known that macrophages' involvement in promoting tissue repair

Cancer cell - Misplaced Pages Continue

2944-828: Is required for certain procedures such as antibody-linked immunofluorescence staining. Frozen sections are often prepared during surgical removal of tumors to allow rapid identification of tumor margins, as in Mohs surgery , or determination of tumor malignancy, when a tumor is discovered incidentally during surgery. Ultramicrotomy is a method of preparing extremely thin sections for transmission electron microscope (TEM) analysis. Tissues are commonly embedded in epoxy or other plastic resin. Very thin sections (less than 0.1 micrometer in thickness) are cut using diamond or glass knives on an ultramicrotome . Artifacts are structures or features in tissue that interfere with normal histological examination. Artifacts interfere with histology by changing

3036-535: Is still up for discussion but studies have shown that their environment allows them to adjust to whichever phenotype is most appropriate to efficiently heal the wound. M2 macrophages are needed for vascular stability. They produce vascular endothelial growth factor-A and TGF-β1 . There is a phenotype shift from M1 to M2 macrophages in acute wounds, however this shift is impaired for chronic wounds. This dysregulation results in insufficient M2 macrophages and its corresponding growth factors that aid in wound repair. With

3128-422: Is used in visualizing the locations to which a radioactive substance has been transported within the body, such as cells in S phase (undergoing DNA replication ) which incorporate tritiated thymidine , or sites to which radiolabeled nucleic acid probes bind in in situ hybridization . For autoradiography on a microscopic level, the slide is typically dipped into liquid nuclear tract emulsion, which dries to form

3220-528: The atheromatous plaque of atherosclerosis. The first step to understanding the importance of macrophages in muscle repair, growth, and regeneration is that there are two "waves" of macrophages with the onset of damageable muscle use– subpopulations that do and do not directly have an influence on repairing muscle. The initial wave is a phagocytic population that comes along during periods of increased muscle use that are sufficient to cause muscle membrane lysis and membrane inflammation, which can enter and degrade

3312-510: The fragment crystallizable (Fc) region of antigen-bound immunoglobulin G (IgG) antibodies. When phagocytosing and digesting pathogens, macrophages go through a respiratory burst where more oxygen is consumed to supply the energy required for producing reactive oxygen species (ROS) and other antimicrobial molecules that digest the consumed pathogens. Recognition of MAMPs by PRRs can activate tissue resident macrophages to secrete proinflammatory cytokines that recruit other immune cells. Among

3404-449: The nucleolus can become enlarged. In normal cells, the nucleus is often round or solid in shape, but in cancer cells the outline is often irregular. Different combinations of abnormalities are characteristic of different cancer types, to the extent that nuclear appearance can be used as a marker in cancer diagnostics and staging . Cancer cells are created when the genes responsible for regulating cell division are damaged. Carcinogenesis

3496-463: The telomeres of most cells shorten after each division, eventually causing the cell to die, telomerase extends the cell's telomeres. This is a major reason that cancer cells can accumulate over time, creating tumors. In February 2019, medical scientists announced that iridium attached to albumin , creating a photosensitized molecule , can penetrate cancer cells and, after being irradiated with light (a process called photodynamic therapy ), destroy

3588-689: The "killer" molecule nitric oxide , whereas M2 macrophages have the unique ability to metabolize arginine to the "repair" molecule ornithine . However, this dichotomy has been recently questioned as further complexity has been discovered. Human macrophages are about 21 micrometres (0.00083 in) in diameter and are produced by the differentiation of monocytes in tissues. They can be identified using flow cytometry or immunohistochemical staining by their specific expression of proteins such as CD14 , CD40 , CD11b , CD64 , F4/80 (mice)/ EMR1 (human), lysozyme M, MAC-1 /MAC-3 and CD68 . Macrophages were first discovered and named by Élie Metchnikoff ,

3680-554: The 17th century the Italian Marcello Malpighi used microscopes to study tiny biological entities; some regard him as the founder of the fields of histology and microscopic pathology. Malpighi analyzed several parts of the organs of bats, frogs and other animals under the microscope. While studying the structure of the lung, Malpighi noticed its membranous alveoli and the hair-like connections between veins and arteries, which he named capillaries. His discovery established how

3772-452: The DNA repair gene DMC1 encodes a protein that is normally expressed only in cells undergoing meiosis where it helps maintain an undamaged germ-line . However, DMC1 is also expressed in various cancer cell lines including cervical, breast, and lymphoma cancer cell lines. Expression of meiotic DNA repair genes such as DMC1 may promote tumor cell growth by dealing with endogenous DNA damage within

Cancer cell - Misplaced Pages Continue

3864-536: The M1 macrophages are unable/do not phagocytose neutrophils that have undergone apoptosis leading to increased macrophage migration and inflammation. Both M1 and M2 macrophages play a role in promotion of atherosclerosis . M1 macrophages promote atherosclerosis by inflammation. M2 macrophages can remove cholesterol from blood vessels, but when the cholesterol is oxidized, the M2 macrophages become apoptotic foam cells contributing to

3956-521: The M2 "repair" designation (also referred to as alternatively activated macrophages) broadly refers to macrophages that function in constructive processes like wound healing and tissue repair, and those that turn off damaging immune system activation by producing anti-inflammatory cytokines like IL-10 . M2 is the phenotype of resident tissue macrophages, and can be further elevated by IL-4 . M2 macrophages produce high levels of IL-10, TGF-beta and low levels of IL-12. Tumor-associated macrophages are mainly of

4048-515: The M2 phenotype, and seem to actively promote tumor growth. Macrophages exist in a variety of phenotypes which are determined by the role they play in wound maturation. Phenotypes can be predominantly separated into two major categories; M1 and M2. M1 macrophages are the dominating phenotype observed in the early stages of inflammation and are activated by four key mediators: interferon-γ (IFN-γ), tumor necrosis factor (TNF), and damage associated molecular patterns (DAMPs). These mediator molecules create

4140-550: The PGs, anti-inflammatory PGE2 and pro-inflammatory PGD2 increase the most after activation, with PGE2 increasing expression of IL-10 and inhibiting production of TNFs via the COX-2 pathway. Neutrophils are among the first immune cells recruited by macrophages to exit the blood via extravasation and arrive at the infection site. Macrophages secrete many chemokines such as CXCL1 , CXCL2 , and CXCL8 (IL-8) that attract neutrophils to

4232-498: The PRRs, TLRs play a major role in signal transduction leading to cytokine production. The binding of MAMPs to TLR triggers a series of downstream events that eventually activates transcription factor NF-κB and results in transcription of the genes for several proinflammatory cytokines, including IL-1β , IL-6 , TNF-α , IL-12B , and type I interferons such as IFN-α and IFN-β. Systemically, IL-1β, IL-6, and TNF-α induce fever and initiate

4324-560: The TCR of T H 1 cells recognize specific antigen peptide-bound MHC class II molecules on macrophages, T H 1 cells 1) secrete IFN-γ and 2) upregulate the expression of CD40 ligand (CD40L), which binds to CD40 on macrophages. These 2 signals activate the macrophages and enhance their ability to kill intracellular pathogens through increased production of antimicrobial molecules such as nitric oxide (NO) and superoxide (O ). This enhancement of macrophages' antimicrobial ability by T H 1 cells

4416-461: The acute phase response in which the liver secretes acute phase proteins . Locally, IL-1β and TNF-α cause vasodilation, where the gaps between blood vessel epithelial cells widen, and upregulation of cell surface adhesion molecules on epithelial cells to induce leukocyte extravasation . Additionally, activated macrophages have been found to have delayed synthesis of prostaglandins (PGs) which are important mediators of inflammation and pain. Among

4508-431: The aged neutrophils. The removal of dying cells is, to a greater extent, handled by fixed macrophages , which will stay at strategic locations such as the lungs, liver, neural tissue , bone, spleen and connective tissue, ingesting foreign materials such as pathogens and recruiting additional macrophages if needed. When a macrophage ingests a pathogen, the pathogen becomes trapped in a phagosome , which then fuses with

4600-532: The block and tissue. Paraffin wax does not always provide a sufficiently hard matrix for cutting very thin sections (which are especially important for electron microscopy). Paraffin wax may also be too soft in relation to the tissue, the heat of the melted wax may alter the tissue in undesirable ways, or the dehydrating or clearing chemicals may harm the tissue. Alternatives to paraffin wax include, epoxy , acrylic , agar , gelatin , celloidin , and other types of waxes. In electron microscopy epoxy resins are

4692-629: The body (e.g., histiocytes , Kupffer cells , alveolar macrophages , microglia , and others), but all are part of the mononuclear phagocyte system . Besides phagocytosis, they play a critical role in nonspecific defense ( innate immunity ) and also help initiate specific defense mechanisms ( adaptive immunity ) 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

SECTION 50

#1732884239619

4784-468: The bone marrow. When intracellular pathogens cannot be eliminated, such as in the case of Mycobacterium tuberculosis , the pathogen is contained through the formation of granuloma , an aggregation of infected macrophages surrounded by activated T cells. The macrophages bordering the activated lymphocytes often fuse to form multinucleated giant cells that appear to have increased antimicrobial ability due to their proximity to T H 1 cells, but over time,

4876-432: The cancer cells. Histological Histology , also known as microscopic anatomy or microanatomy , is the branch of biology that studies the microscopic anatomy of biological tissues . Histology is the microscopic counterpart to gross anatomy , which looks at larger structures visible without a microscope . Although one may divide microscopic anatomy into organology , the study of organs, histology ,

4968-535: The cells in the center start to die and form necrotic tissue. T H 2 cells play an important role in alternative macrophage activation as part of type 2 immune response against large extracellular pathogens like helminths . T H 2 cells secrete IL-4 and IL-13, which activate macrophages to become M2 macrophages, also known as alternatively activated macrophages. M2 macrophages express arginase-1 , an enzyme that converts arginine to ornithine and urea . Ornithine help increase smooth muscle contraction to expel

5060-430: The cell’s DNA, may cause replication errors, including mutations that lead to cancer. Numerous inherited DNA repair disorders have been described that increase cancer risk (see Misplaced Pages article DNA repair-deficiency disorder ). In addition, particular DNA repair enzymes have been found to be deficient in multiple cancers. For example, deficient expression of the DNA repair enzyme O-6-methylguanine-DNA methyltransferase

5152-720: The co-stimulatory signal. These interactions allow T helper cells to achieve full effector function and provide T helper cells with continued survival and differentiation signals preventing them from undergoing apoptosis due to lack of TCR signaling. For example, IL-2 signaling in T cells upregulates the expression of anti-apoptotic protein Bcl-2 , but T cell production of IL-2 and the high-affinity IL-2 receptor IL-2RA both require continued signal from TCR recognition of MHC-bound antigen. Macrophages can achieve different activation phenotypes through interactions with different subsets of T helper cells, such as T H 1 and T H 2. Although there

5244-407: The condition as blood disease, and named it leukämie in 1847 (later anglicised to leukemia ). In 1857, he was the first to describe a type of tumour called chordoma that originated from the clivus (at the base of the skull ). Cancer cells have unique features that make them "immortal" according to some researchers. The enzyme telomerase is used to extend the cancer cell's life span. While

5336-452: The contents of injured muscle fibers. These early-invading, phagocytic macrophages reach their highest concentration about 24 hours following the onset of some form of muscle cell injury or reloading. Their concentration rapidly declines after 48 hours. The second group is the non-phagocytic types that are distributed near regenerative fibers. These peak between two and four days and remain elevated for several days during while muscle tissue

5428-495: The electron microscope. Similar to the frozen section procedure employed in medicine, cryosectioning is a method to rapidly freeze, cut, and mount sections of tissue for histology. The tissue is usually sectioned on a cryostat or freezing microtome. The frozen sections are mounted on a glass slide and may be stained to enhance the contrast between different tissues. Unfixed frozen sections can be used for studies requiring enzyme localization in tissues and cells. Tissue fixation

5520-407: The exposure film. Individual silver grains in the film are visualized with dark field microscopy . Recently, antibodies have been used to specifically visualize proteins, carbohydrates, and lipids. This process is called immunohistochemistry , or when the stain is a fluorescent molecule, immunofluorescence . This technique has greatly increased the ability to identify categories of cells under

5612-431: The extracellular space that can then be killed by other activated macrophages. T H 1 cells also help recruit more monocytes, the precursor to macrophages, to the infection site. T H 1 secretion TNF-α and LT-α to make blood vessels easier for monocytes to bind to and exit. T H 1 secretion of CCL2 as a chemoattractant for monocytes. IL-3 and GM-CSF released by T H 1 cells stimulate more monocyte production in

SECTION 60

#1732884239619

5704-538: The formation of methylene bridges (-CH 2 -), in the case of formaldehyde, or by C 5 H 10 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, particularly enzymes . Formalin fixation leads to degradation of mRNA, miRNA, and DNA as well as denaturation and modification of proteins in tissues. However, extraction and analysis of nucleic acids and proteins from formalin-fixed, paraffin-embedded tissues

5796-652: The four categories currently accepted by histologists. The usage of illustrations in histology, deemed as useless by Bichat, was promoted by Jean Cruveilhier . In the early 1830s Purkynĕ invented a microtome with high precision. During the 19th century many fixation techniques were developed by Adolph Hannover (solutions of chromates and chromic acid ), Franz Schulze and Max Schultze ( osmic acid ), Alexander Butlerov ( formaldehyde ) and Benedikt Stilling ( freezing ). Mounting techniques were developed by Rudolf Heidenhain (1824–1898), who introduced gum Arabic ; Salomon Stricker (1834–1898), who advocated

5888-409: The function of that organ. In the testis , for example, macrophages have been shown to be able to interact with Leydig cells by secreting 25-hydroxycholesterol , an oxysterol that can be converted to testosterone by neighbouring Leydig cells. Also, testicular macrophages may participate in creating an immune privileged environment in the testis, and in mediating infertility during inflammation of

5980-567: The general structure), the term histochemistry is used. Hematoxylin and eosin ( H&E stain ) is one of the most commonly used stains in histology to show the general structure of the tissue. Hematoxylin stains cell nuclei blue; eosin, an acidic dye, stains the cytoplasm and other tissues in different stains of pink. In contrast to H&E, which is used as a general stain, there are many techniques that more selectively stain cells, cellular components, and specific substances. A commonly performed histochemical technique that targets

6072-414: The haemoglobin is either stored internally in ferritin or is released into the circulation via ferroportin . In cases where systemic iron levels are raised, or where inflammation is present, raised levels of hepcidin act on macrophage ferroportin channels, leading to iron remaining within the macrophages. Melanophages are a subset of tissue-resident macrophages able to absorb pigment, either native to

6164-429: The immune system, macrophages also play an important anti-inflammatory role and can decrease immune reactions through the release of cytokines . Macrophages that encourage inflammation are called M1 macrophages, whereas those that decrease inflammation and encourage tissue repair are called M2 macrophages. This difference is reflected in their metabolism; M1 macrophages have the unique ability to metabolize arginine to

6256-761: The interaction between CD40 on the macrophages and CD40L on T cells activate macrophages to secrete IL-12; and IL-12 promotes more IFN-γ secretion from T H 1 cells. The initial contact between macrophage antigen-bound MHC II and TCR serves as the contact point between the two cells where most of the IFN-γ secretion and CD-40L on T cells concentrate to, so only macrophages directly interacting with T H 1 cells are likely to be activated. In addition to activating M1 macrophages, T H 1 cells express Fas ligand (FasL) and lymphotoxin beta (LT-β) to help kill chronically infected macrophages that can no longer kill pathogens. The killing of chronically infected macrophages release pathogens to

6348-485: The lymph node and arrived at the site of infection or with tissue resident memory T cells. Macrophages supply both signals required for T helper cell activation: 1) Macrophages present antigen peptide-bound MHC class II molecule to be recognized by the corresponding T cell receptor (TCR), and 2) recognition of pathogens by PRRs induce macrophages to upregulate the co-stimulatory molecules CD80 and CD86 (also known as B7 ) that binds to CD28 on T helper cells to supply

6440-507: The lymph nodes where naïve T helper cells reside. Although macrophages are also found in secondary lymphoid organs like the lymph nodes, they do not reside in T cell zones and are not effective at activating naïve T helper cells. The macrophages in lymphoid tissues are more involved in ingesting antigens and preventing them from entering the blood, as well as taking up debris from apoptotic lymphocytes. Therefore, macrophages interact mostly with previously activated T helper cells that have left

6532-446: The macrophages that accumulate at diseased sites typically derive from circulating monocytes. Leukocyte extravasation describes monocyte entry into damaged tissue through the endothelium of blood vessels as they become macrophages. Monocytes are attracted to a damaged site by chemical substances through chemotaxis , triggered by a range of stimuli including damaged cells, pathogens and cytokines released by macrophages already at

6624-412: The main constituent of biological tissue, so it must first be removed in a series of dehydration steps. Samples are transferred through a series of progressively more concentrated ethanol baths, up to 100% ethanol to remove remaining traces of water. Dehydration is followed by a clearing agent (typically xylene although other environmental safe substitutes are in use ) which removes the alcohol and

6716-440: The most commonly employed embedding media, but acrylic resins are also used, particularly where immunohistochemistry is required. For tissues to be cut in a frozen state, tissues are placed in a water-based embedding medium. Pre-frozen tissues are placed into molds with the liquid embedding material, usually a water-based glycol, OCT , TBS , Cryogen, or resin, which is then frozen to form hardened blocks. For light microscopy,

6808-610: The neural structure of the brain based on differing interpretations of the same images. Ramón y Cajal won the prize for his correct theory, and Golgi for the silver-staining technique that he invented to make it possible. There is interest in developing techniques for in vivo histology (predominantly using MRI ), which would enable doctors to non-invasively gather information about healthy and diseased tissues in living patients, rather than from fixed tissue samples. Macrophages Macrophages ( / ˈ m æ k r oʊ f eɪ dʒ / ; abbreviated M φ , MΦ or MP ) are

6900-605: The oldest documented malignant hominin cancer. The understanding of cancer was significantly advanced during the Renaissance period and in to the Age of Discovery . Sir Rudolf Virchow , a German biologist and politician , studied microscopic pathology, and linked his observations to illness. He is described as "the founder of cellular pathology". In 1845, Virchow and John Hughes Bennett independently observed abnormal increase in white blood cells in patients. Virchow correctly identified

6992-404: The organism or exogenous (such as tattoos ), from extracellular space. In contrast to dendritic juncional melanocytes , which synthesize melanosomes and contain various stages of their development, the melanophages only accumulate phagocytosed melanin in lysosome-like phagosomes. This occurs repeatedly as the pigment from dead dermal macrophages is phagocytosed by their successors, preserving

7084-456: The oxygen breathed in enters the blood stream and serves the body. In the 19th century histology was an academic discipline in its own right. The French anatomist Xavier Bichat introduced the concept of tissue in anatomy in 1801, and the term "histology" ( German : Histologie ), coined to denote the "study of tissues", first appeared in a book by Karl Meyer in 1819. Bichat described twenty-one human tissues, which can be subsumed under

7176-440: The preparation of tissues for microscopic examination is known as histotechnology. Job titles for the trained personnel who prepare histological specimens for examination are numerous and include histotechnicians, histotechnologists, histology technicians and technologists, medical laboratory technicians , and biomedical scientists . Most histological samples need preparation before microscopic observation; these methods depend on

7268-823: The production of proinflammatory cytokine interferon gamma (IFN-γ) by NK cells, which serves as an important source of IFN-γ before the adaptive immune system is activated. IFN-γ enhances the innate immune response by inducing a more aggressive phenotype in macrophages, allowing macrophages to more efficiently kill pathogens. Some of the T cell chemoattractants secreted by macrophages include CCL5 , CXCL9 , CXCL10 , and CXCL11 . Macrophages are professional antigen presenting cells (APC), meaning they can present peptides from phagocytosed antigens on major histocompatibility complex (MHC) II molecules on their cell surface for T helper cells. Macrophages are not primary activators of naïve T helper cells that have never been previously activated since tissue resident macrophages do not travel to

7360-665: The site of infection. After neutrophils have finished phagocytosing and clearing the antigen at the end of the immune response, they undergo apoptosis, and macrophages are recruited from blood monocytes to help clear apoptotic debris. Macrophages also recruit other immune cells such as monocytes, dendritic cells, natural killer cells, basophils, eosinophils, and T cells through chemokines such as CCL2 , CCL4 , CCL5 , CXCL8 , CXCL9 , CXCL10 , and CXCL11 . Along with dendritic cells, macrophages help activate natural killer (NK) cells through secretion of type I interferons (IFN-α and IFN-β) and IL-12 . IL-12 acts with IL-18 to stimulate

7452-523: The site. At some sites such as the testis, macrophages have been shown to populate the organ through proliferation. Unlike short-lived neutrophils , macrophages survive longer in the body, up to 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 chronic inflammation, as the early stages of inflammation are dominated by neutrophils, which are ingested by macrophages if they come of age (see CD31 for

7544-401: The specimen and method of observation. Chemical fixatives are used to preserve and maintain the structure of tissues and cells; fixation also hardens tissues which aids in cutting the thin sections of tissue needed for observation under the microscope. Fixatives generally preserve tissues (and cells) by irreversibly cross-linking proteins. The most widely used fixative for light microscopy

7636-610: The study of tissues, and cytology , the study of cells , modern usage places all of these topics under the field of histology. In medicine , histopathology is the branch of histology that includes the microscopic identification and study of diseased tissue. In the field of paleontology , the term paleohistology refers to the histology of fossil organisms. There are four basic types of animal tissues: muscle tissue , nervous tissue , connective tissue , and epithelial tissue . All animal tissues are considered to be subtypes of these four principal tissue types (for example, blood

7728-463: The surface of the cell. These work to help macrophages detect and kill cancer cells. Early evidence of human cancer can be interpreted from Egyptian papers (1538 BCE) and mummified remains. In 2016, a 1.7 million year old osteosarcoma was reported by Edward John Odes (a doctoral student in Anatomical Sciences from Witwatersrand Medical School, South Africa) and colleagues, representing

7820-411: The tattoo in the same place. Every tissue harbors its own specialized population of resident macrophages, which entertain reciprocal interconnections with the stroma and functional tissue. These resident macrophages are sessile (non-migratory), provide essential growth factors to support the physiological function of the tissue (e.g. macrophage-neuronal crosstalk in the guts), and can actively protect

7912-643: The testis. Cardiac resident macrophages participate in electrical conduction via gap junction communication with cardiac myocytes . Macrophages can be classified on basis of the fundamental function and activation. According to this grouping, there are classically activated (M1) macrophages , wound-healing macrophages (also known as alternatively-activated (M2) macrophages ), and regulatory macrophages (Mregs). Macrophages that reside in adult healthy tissues either derive from circulating monocytes or are established before birth and then maintained during adult life independently of monocytes. By contrast, most of

8004-427: The tissue from inflammatory damage. Nerve-associated macrophages or NAMs are those tissue-resident macrophages that are associated with nerves. Some of them are known to have an elongated morphology of up to 200μm Due to their role in phagocytosis, macrophages are involved in many diseases of the immune system. For example, they participate in the formation of granulomas , inflammatory lesions that may be caused by

8096-436: The tissues appearance and hiding structures. Tissue processing artifacts can include pigments formed by fixatives, shrinkage, washing out of cellular components, color changes in different tissues types and alterations of the structures in the tissue. An example is mercury pigment left behind after using Zenker's fixative to fix a section. Formalin fixation can also leave a brown to black pigment under acidic conditions. In

8188-420: The tumor, and may also diminish the effectiveness of anticancer therapy, such as radiation therapy . Cells playing roles in the immune system, such as T-cells , are thought to use a dual receptor system when they determine whether or not to kill sick or damaged human cells. If a cell is under stress, turning into tumors, or infected, molecules including MIC-A and MIC-B are produced so that they can attach to

8280-656: The worm and also participates in tissue and wound repair. Ornithine can be further metabolized to proline , which is essential for synthesizing collagen . M2 macrophages can also decrease inflammation by producing IL-1 receptor antagonist (IL-1RA) and IL-1 receptors that do not lead to downstream inflammatory signaling (IL-1RII). Another part of the adaptive immunity activation involves stimulating CD8 via cross presentation of antigens peptides on MHC class I molecules. Studies have shown that proinflammatory macrophages are capable of cross presentation of antigens on MHC class I molecules, but whether macrophage cross-presentation plays

8372-401: The wound peak one to one and a half days after the injury occurs. Once they are in the wound site, monocytes mature into macrophages. The spleen contains half the body's monocytes in reserve ready to be deployed to injured tissue. The macrophage's main role is to phagocytize bacteria and damaged tissue, and they also debride damaged tissue by releasing proteases. Macrophages also secrete

8464-450: The wound, create granulation tissue, and lay down a new extracellular matrix . By secreting these factors, macrophages contribute to pushing the wound healing process into the next phase. Scientists have elucidated that as well as eating up material debris, macrophages are involved in the typical limb regeneration in the salamander. They found that removing the macrophages from a salamander resulted in failure of limb regeneration and

#618381