5) Connective2324 les 5.pptx

Bindweefsel Hoofdfunctie BW: voorzien en onderhouden van vorm en stevigheid in het lichaam Mechanische rol: Verbinden van cellen en organen >Het lichaam ondersteunen 3 structurele componenten: > cellen, > vezels, > grondsubstantie Vooral extracellulaire matrix!!! >> proteïne vezels (collageen, ret...

Bindweefsel Hoofdfunctie BW: voorzien en onderhouden van vorm en stevigheid in het lichaam Mechanische rol: Verbinden van cellen en organen >Het lichaam ondersteunen 3 structurele componenten: > cellen, > vezels, > grondsubstantie Vooral extracellulaire matrix!!! >> proteïne vezels (collageen, reticulair and elastische vezels) & >> grondsubstantie: hydrofiel, visceus >>> anionische macromolecules >>>>glycosaminoglycanen >>> >proteoglycanen >>> multiadhesive glycoproteins: binden op integrines op het celoppervlak BW is een uitwisselings medium tussen cellen en de bloedbaan BW: herstel na beschadiging Diversiteit van BW types door variatie in de samenstelling en respectieve hoeveelheid van de 3 componenten Figure 5–30. Electron micrograph showing the structural organization of the connective tissue matrix. The ground substance is a fine granular material that fills the spaces between the collagen (C) and elastic (E) fibers and surrounds fibroblast cells and processes (F). The granularity of ground substance is an artifact of the glutaraldehyde–tannic acid fixation procedure. x100,000. Cellular and extracellular components of connective tissue. Connective tissue is composed of fibroblasts and other cells and an ECM of various protein fibers, all of which are surrounded by watery ground substance. In all types of connective tissue, the extracellular volume exceeds that of the cells. CELLEN VAN HET BINDWEEFSEL Permanente BW cellen > < tijdelijke bewoners Figure 5–1. Simplified representation of the connective tissue cell lineage derived from the multipotential embryonic mesenchyme cell. Dotted arrows indicate that intermediate cell types exist between the examples illustrated. Note that the cells are not drawn in proportion to actual sizes, eg, adipocyte, megakaryocyte, and osteoclast cells are significantly larger than the other cells illustrated. (1) Fibroblasten(5-3), (5-4), (5-5) Synthetiseren de extracellulaire matrix componenten > collageen > elastine > Glycosaminoglycanen ( koolydraten) > multiadhesive glycoproteïnen (eiwit met suiker antene) afiniteit met alles wat ze tegen komen) Fibroblast = actieve cel > < fibrocyt = minder actief Kenmerken van een fibroblast: > aanzienlijke hoeveelheid cytoplasma (vertakte cel) > grote, ovale nucleus > prominente nucleolus > veel RER > goed ontwikkeld Golgi complex Fibrocyt: kleiner met minder ontwikkelde celcomponenten Figure 5–2. Section of rat skin. A connective tissue layer (dermis) shows several fibroblasts (F), which are the elongated cells. H&E stain. Medium magnification. Figure 5–3. Quiescent fibroblasts are elongated cells with thin cytoplasmic extensions and condensed chromatin. Pararosaniline-toluidine blue (PT) stain. Medium magnification. Figure 5–4. Active (left) and quiescent (right) fibroblasts. External morphologic characteristics and ultrastructure of each cell are shown. Fibroblasts that are actively engaged in synthesis are richer in mitochondria, lipid droplets, Golgi complex, and rough endoplasmic reticulum than are quiescent fibroblasts (fibrocytes). Figure 5–5. Electron micrograph revealing portions of several flattened fibroblasts in dense connective tissue. Abundant mitochondria, rough endoplasmic reticulum, and vesicles distinguish these cells from the less active fibrocytes. Multiple strata of collagen fibrils (C) lie among the fibroblasts. x30,000. Fibroblasts. (a)Fibroblasts typically have large active nuclei and eosinophilic cytoplasm that tapers off in both directions along the axis of the nucleus, a morphology often referred to as “spindle-shaped.” Nuclei (arrows) are clearly seen, but the eosinophilic cytoplasmic processes resemble the collagen bundles (C) that fill the ECM and are difficult to distinguish in H&E-stained sections. (b)Both active and quiescent fibroblasts may sometimes be distinguished, as in this section of dermis. Active fibroblasts have large, euchromatic nuclei and basophilic cytoplasm, while inactive fibroblasts (or fibrocytes) are smaller with more heterochromatic nuclei (arrows). The round, very basophilic round cells are in leukocytes. (Both X400; H&E) Fibroblasts. (a)Fibroblasts typically have large active nuclei and eosinophilic cytoplasm that tapers off in both directions along the axis of the nucleus, a morphology often referred to as “spindle-shaped.” Nuclei (arrows) are clearly seen, but the eosinophilic cytoplasmic processes resemble the collagen bundles (C) that fill the ECM and are difficult to distinguish in H&E-stained sections. (b)Both active and quiescent fibroblasts may sometimes be distinguished, as in this section of dermis. Active fibroblasts have large, euchromatic nuclei and basophilic cytoplasm, while inactive fibroblasts (or fibrocytes) are smaller with more heterochromatic nuclei (arrows). The round, very basophilic round cells are in leukocytes. (Both X400; H&E) (2) Macrofagen (5-6), (5-7), (5-8) Kenmerken: > Onregelmatig oppervlak: met veel uitstulpingen = endocytose activiteit > Goed ontwikkeld GC > Veel lysosomen > Prominent RER Macrofagen zijn afgeleid van monocyten die in het bloed circuleren. >Monocyten verlaten de capillairen en penetreren het BW waar ze verdere maturatie ondergaan. > Lang levende cellen = Kupffer cellen, microglia cellen, Langerhans cellen, osteoclasten. Van monocyt naar macrofaag=> toename van GC, # of lysosomen, # microtubulen, # microfilamenten. Figure 5–6. Section of pancreas from a rat injected with the vital dye trypan blue. Note that 3 macrophages (arrows) have engulfed and accumulated the dye in the form of granules. H&E stain. Low magnification. Figure 5–7. Electron micrograph of a macrophage. Note the secondary lysosomes (L), the nucleus (N), and the nucleolus (Nu). The arrows indicate phagocytic vacuoles. Figure 5–8. Electron micrograph of several macrophages and 2 eosinophils in a region adjacent to a tumor. This figure illustrates the participation of macrophages in tissue reaction to tumor invasion. (3) Mestcellen (5-10) Eigenschappen:  Gepakt met secreet granula ( zit heel veel granula in )  Centrale, ronde nucleus De granula bevatten mediatoren (bv. Histamine) en proteasen( kan proteïne kapotmaken) , eosinofiel chemotactische factoren, neutrofiel chemotactische factoren.  Functie: stockeren van chemische mediatoren van de ontstekingsreactie  Mestcellen stellen leukotriënen vrij (aangemaakt uit membraan fosfolipiden) >Paracrine secretie ( nauwe omgeving ) Figure 5–10. Section of rat tongue. Several mast cells in the connective tissue surround muscle cells and blood vessels. PT stain. Medium magnification. Figure 5–11. Electron micrograph of a human mast cell. The granules (G) contain heparin and histamine. Note the characteristic scroll-like structures within the granules. M, mitochondrion; C, collagen fibrils; E, elastic fibril; N, nucleus. x14,700. Inset: Higher magnification view of a mast cell granule. x44,600. (Courtesy of MC Williams.) Figure 5–12. Mast-cell secretion. 1: IgE molecules are bound to the surface receptors. 2: After a second exposure to an antigen (eg, bee venom), IgE molecules bound to surface receptors are cross-linked by the antigen. This activates adenylate cyclase and results in the phosphorylation of certain proteins. 3: At the same time, Ca2+ enters the cell. 4: These events lead to intracellular fusion of specific granules and exocytosis of their contents. 5: In addition, phospholipases act on membrane phospholipids to produce leukotrienes. The process of extrusion does not damage the cell, which remains viable and synthesizes new granules. ECF-A, eosinophil chemotactic factor of anaphylaxis. (4) Plasma cells (5-13), (5-14), (5-15) Eigenschappen > Grote, ovale cellen, met veel RER (synthese van Antilichamen) (5) Adipose cells (6-1), (6-5) Figure 5–13. Portion of a chronically inflamed intestinal villus. The plasma cells are characterized by their size and abundant basophilic cytoplasm (rough endoplasmic reticulum) and are involved in the synthesis of antibodies. A large Golgi complex (arrows) is where the terminal glycosylation of the antibodies (glycoproteins) occurs. Plasma cells produce antibodies of importance in immune reactions. PT stain. Medium magnification. Figure 5–14. Ultrastructure of a plasma cell. The cell contains a well-developed rough endoplasmic reticulum, with dilated cisternae containing immunoglobulins (antibodies). In plasma cells, the secreted proteins do not aggregate into secretory granules. Nu, nucleolus. (Redrawn and reproduced, with permission, from Ham AW: Histology, 6th ed. Lippincott, 1969.) Figure 5–15. Electron micrograph of a plasma cell showing an abundance of rough endoplasmic reticulum (R). Note that many cisternae are dilated. Four profiles of the Golgi complex (G) are observed near the nucleus (N). M, mitochondria. (Courtesy of P. Abrahamsohn.) Plasma cells. Antibody-secreting plasma cells are present in variable numbers in the connective tissue of many organs. (a)Plasma cells are large, ovoid cells, with basophilic cytoplasm. The round nuclei frequently show peripheral clumps of heterochromatin, giving the structure a “clock-face” appearance. (X640; H&E) (b)Plasma are often more abundant in infected tissues, as in the inflamed lamina propria shown here. A large pale Golgi apparatus (arrows) at a juxtanuclear site in each cell is actively involved in the terminal glycosylation of the antibodies (glycoproteins). Plasma cells leave their sites of origin in lymphoid tissues, move to connective tissue, and produce antibodies that mediate immunity. (X400; PT) (6) Leukocytes (12-10) Eosinofielen: > bevatten basische proteïnen >> doden van parasieten > produceren substanties die de onstekingsreactie mediëren >> inactivatie van histamines, leukotriënen > fagocytose van AG-AL-complexen Migratie uit de bloedbaan: diapedesis Figure 5–16. Section of an inflamed intestinal lamina propria. Inflammation was caused by nematode parasitism. Aggregated eosinophils and plasma cells function mainly in the connective tissue by modulating the inflammatory process. Giemsa stain. Low magnification. VEZELS Proteïnen die polymeriseren tot langgerekte structuren (1) collagene vezels (2) reticulaire vezels (3) elastische vezels De mix van (1), (2), (3) is gerelateerd met de specifieke eigenschappen van het weefsel. (1) Collageen Collageen is het meest voorkomende proteïne in het menselijk lichaam Classificatie naar functie en structuur a) Collageen dat lange fibrillen vormt (5-17) Verschillende types (I, II, III, V, XI) met type I als het meest voorkomende type. Collagene vezels in bot, dentine, pezen, kapsels rond organen, de dermis b) Fibril-geässocieerde collageen korte structuren die collageen fibrillen binden > aan elkander >aan de extracellulaire matrix Types (IX, XII, XIV) c) Collageen dat netwerken vormt Collageen type IV: moleculen assembleren in een netwerk dat deel uitmaakt van de lamina basalis d) Collageen dat verankeringsvezels vormt Collageen type VII,aanwezig in verankerings fibrilen die collageen vezels binden op de lamina basalis Figure 5–17. Electron micrograph of human collagen fibrils in cross and longitudinal sections. Each fibril consists of regular alternating dark and light bands that are further divided by cross-striations. Ground substance completely surrounds the fibrils. x100,000. Figure 5–18. In the most abundant form of collagen, type I, each molecule (tropocollagen) is composed of two alpha1 and one alpha2 peptide chains, each with a molecular mass of approximately 100 kDa, intertwined in a right-handed helix and held together by hydrogen bonds and hydrophobic interactions. Each complete turn of the helix spans a distance of 8.6 nm. The length of each tropocollagen molecule is 280 nm, and its width is 1.5 nm. Collageen synthese Niet alleen de fibroblasten produceren collageen! aminozuren: > glycine (33.5%) > proline (12%) > hydroxyproline (10%) Hydroxyproline en hydroxylysine zijn specifiek voor collageen De eenheid die polymeriseert is Tropocollageen: > 3 polypeptide ketens gewonden in een triple helix >de chemische structuur van de subeenheden is verantwoordelijk voor de verschillende vormen Tropocollageen moleculen aggregeren tot microfibrilaire eenheden die gestapeld worden om fibrillen te vormen. Versterking van de structuur door covalente cross-links Collageen fibrillen hebben een dwarse streping met een typische periodiciteit van 64nm Figure 5–19. Schematic drawing of an aggregate of collagen molecules (tropocollagen), fibrils, fibers, and bundles. There is a stepwise overlapping arrangement of rodlike tropocollagen subunits, each measuring 280 nm (1). This arrangement results in the production of alternating lacunar and overlapping regions (2) that cause the cross-striations characteristic of collagen fibrils and confer a 64-nm periodicity of dark and light bands when the fibril is observed in the electron microscope (3). Fibrils aggregate to form fibers (4), which aggregate to form bundles (5) routinely called collagen fibers. Collagen type III usually does not form bundles. Assembly of type I collagen. Shown here are the relationships among type I collagen molecules, fibrils, fibers, and bundles. Rodlike triple-helix collagen molecules, each 300-nm long, self-assemble in a highly organized, lengthwise arrangement of overlapping regions. The regular, overlapping arrangement of subunits continues as large collagen fibrils are assembled. This structure causes fibrils to have characteristic cross striations with alternating dark and light bands when observed in the EM. Fibrils assemble further and are linked together in larger collagen fibers visible by light microscopy. Type I fibers often form into still larger aggregates bundled and linked together by other collagens. Figure 5–20. Electron micrograph of hyaline cartilage matrix showing the fine collagen fibrils of collagen type II interspersed with abundant ground substance. Transverse striations of the fibrils are barely visible because of the interaction of collagen with chondroitin sulfate. In the center is a portion of a chondrocyte. Compare the appearance of these fibrils with those of fibrocartilage (see Figure 7–8 in Chapter 7). Biosynthese van collageen (5-21) > polypetide ketens gevormd op polyribosomen (RER) > geïnjecteerd in de cisternae als preprocollageen > verwijdering van de signaalsequentie en vorming van procollageen Stap 2: > hydroxylatie van proline en lysine (co-factor: vit C) Stap 3: > Glycolisatie van hydroxylysine (# en type KH in functie van het collageen type) Stap 4: > de registratiepeptides verzekeren een correcte assemblering van de ketens > de registratiepeptides verzekeren de oplosbaarheid > de registratiepeptides voorkomen een intracellulaire assemblage > procollageen wordt uit de cel getransporteerd Stap 5: >procollageen peptidasen verwijderen de registratiepeptiden zodat tropocollageen ontstaat > tropocollageen kan dan assembleren tot polymere collageen fibrillen Stap 6: > Collageen fibrillen aggregeren spontaan om vezels te vormen. Stap 7: > Fibrillaire structuren worden versterkt door covalente cross-links tussen tropocollageen molecules. Collageen vernieuwing is in het algemeen een traag proces: > Stabiele collageen in pezen en ligamenten > periodontale ligamenten hebben een hoge turn over!!! Degradatie door collagenases. Na 1 actie van het enzym collagenase kunnen normale proteases de collageen vezels afbreken. In vele plaatsen van het lichaam worden collagenevezels parallel georganiseerd tot bundels. (523) (5-24) Stap 1: Figure 5–21. Collagen synthesis. The assembly of the triple helix and the hydroxylation and glycosylation of procollagen molecules are simultaneous processes that begin as soon as the 3 chains cross the membrane of the rough endoplasmic reticulum (RER). Because collagen synthesis depends on the expression of several genes and on several post-translation events, many collagen diseases have been described. Figure 5–23. Dense irregular connective tissue from human dermis contains thick bundles of collagen fibers, fibroblast nuclei (arrowheads), and a few small blood vessels (bv). H&E stain. Medium magnification. Type I collagen. (b) The large bundles of type I collagen fibrils (C) appear as acidophilic collagen fibers in connective tissues, where they may fill the extracellular space. Subunits for these fibers were secreted by the fibroblasts (arrows) associated with them. (X400; H&E) (2) Reticulaire vezels > Bevatten vooral type III collageen vezels (5-22) (5-24) > Extreem dun (0.5 to 2 µm) > Vormen een ruimtelijk netwerk > Bevatten tot 12% hexosen (slechts 1% in collageen vezels) > netwerk: een combinatie van >> type III collageen >> glycoproteïnen voor interfibrillaire bruggen >> proteoglycanen voor interfibrillaire bruggen => Vormen van een flexibel netwerk in gladde spieren, endoneurium, bloedvormende organen (5-25), (5-26) Figure 5–22. Section of a muscular artery stained with picro-sirius and observed with polarization optics. The upper tunica media (muscular layer) contains reticular fibers consisting mainly of collagen type III. The lower layer (tunica adventitia) contains thick fibers and bundles of collagen type I. Deficiencies of collagen type III may result in rupture of the arterial wall. Medium magnification. Figure 5–25. Section of an adrenal cortex, silver stained to show reticular fibers. This is a thick section made to emphasize the networks formed by these fibers, which consist of collagen type III. Nuclei are black, and cytoplasm is unstained. Medium magnification. Figure 5–26. Electron micrograph of cross sections of reticular (left) and collagen (right) fibers. Note that each fiber type is composed of numerous smaller collagen fibrils. Reticular fibrils (R) are significantly narrower in diameter than collagen fibrils of collagen fibers (C; see histogram inset); in addition, the constituent fibrils of the reticular fibers reveal an abundant surface-associated granularity not present on regular collagen fibrils (right). x70,000. (3) Elastische vezels (5-27) (5-28) Wordt gevormd uit 3 types vezels: > Oxytalan > Elaunine > Elastische Ontwikkeling van het elastisch netwerk: Fase 1: Oxytalanvezels onstaan uit bundels van microfibrillen die agregeren : verschillende glycoproteinen waaronder fibrilline (netwerk voor elastine dispositie). Fase 2: een dispositie van elastine tussen de oxytalanvezels (ontstaan van elauninevezels) Fase 3: elastine hoopt zich op tot in het centrum van de elauninevezels, die omringd blijven door een dunne laag microfibrillen Oxytalan vezels zijn niet elastisch en weerstaan aan trekkrachten Elastische vezels stretchen gemakkelijk: (5-29) De verschillende verhouding tussen microfibrillen en elastine zorgen voor eigenschappen aangepast aan de locale weefsel vereisten. Proelastine is een globulaire molecule die polymeriseert en alzo elastine vormt (amorf rubberachtige glycoproteine). Elastine bevat veel glycine en proline en 2 ongewone aminozuren: desmosine en isodesmosine (covalente reacties tussen lysine residues) => cross linking Figure 5–24. A: Total preparation of young rat mesentery showing red picrosirius-stained nonanastomosing bundles of collagen fibers, while the elastic fibers appear as thin, dark anastomosing fibers stained by orcein. Collagen and elastic fibers provide structure and elasticity, respectively, to the mesentery. Medium magnification. B: The same preparation observed with polarizing microscopy. Collagen bundles of various thicknesses are observed. In the superimposed regions, the bundles of collagen are a dark color. Medium magnification. Figure 5–27. Skin dermis, selectively stained for elastic fibers. Dark elastic fibers are interspersed with pale red collagen fibers. The elastic fibers are responsible for skin’s elasticity. Medium magnification. Figure 5–28. Electron micrographs of developing elastic fibers. A: In early stages of formation, developing fibers consist of numerous small glycoprotein microfibrils. B: With further development, amorphous aggregates of elastin are found among the microfibrils. C: The amorphous elastin accumulates, ultimately occupying the center of an elastic fiber delineated by microfibrils. Note the collagen fibrils, seen in cross section. (Courtesy of GS Montes.) Figure 5–29. Elastin molecules are joined by covalent bonds to generate an extensive cross-linked network. Because each elastin molecule in the network can expand and contract like a random coil, the entire network can stretch and recoil like a rubber band. (Reproduced, with permission, from Alberts B et al: Molecular Biology of the Cell. Garland, 1983.) Elastic fibers. Elastic fibers or lamellae (sheets) add resiliency to connective tissue. Such fibers may be difficult to discern in H&E-stained tissue, but elastin has a distinct, darker-staining appearance with other staining procedures. (a)The length, diameter, distribution, and density of dark elastic fibers are easily seen in this spread preparation of nonstretched connective tissue in a mesentery. (X200; Hematoxylin and orcein) (b)In sectioned tissue at higher magnification, elastic fibers can be seen among the acidophilic collagen bundles of dermis. (X400; Aldehyde fuchsin) (c)Elastic lamellae in the wall of the aorta are more darkly stained, incomplete sheets of elastin between the layers of eosinophilic smooth muscle. (X80; H&E) GRONDSUBSTANTIE De intercellulaire grondsubstantie is sterk gehydrateerd Componenten: > Glycosaminoglycanen (repetitieve disachariden) > proteoglycanen (GAG + eiwit) > multiadhesive glycoproteïnen Vult de ruimte op tussen de cellen en de vezels (5-30) (5-31) De grondsubstantie heeft een hoge viscositeit: > smeermiddel > barrière Figure 5–30. Electron micrograph showing the structural organization of the connective tissue matrix. The ground substance is a fine granular material that fills the spaces between the collagen (C) and elastic (E) fibers and surrounds fibroblast cells and processes (F). The granularity of ground substance is an artifact of the glutaraldehyde–tannic acid fixation procedure. x100,000. Ground substance of the ECM. (a)TEM of connective tissue ECM reveals ground substance as areas containing only fine granular material among the collagen (C) fibers, elastic (E) fibers, and fibroblast processes (F). X100,000. (b)As shown here schematically, connective tissue ground substance contains a vast complex of proteoglycans linked to very long hyaluronan molecules. Each proteoglycan monomer has a core protein with a few or many side chains of the sulfated GAGs listed in Table 5–5. Synthesized in the RER and Golgi apparatus like glycoproteins, proteoglycan monomers are distinguished by often being more heavily glycosylated and by the addition and sulfation of GAGs, which vary significantly among proteoglycans in their number, length, and the degree to which the sugar polymers are modified. Aggrecan, the most abundant and important proteoglycan in the articular cartilage of joints (see Chapter 8), is a very large macromolecule with a 250 kDa core protein approximately 400 nm long with roughly 100 chondroitin sulfate side chains, each 20 kDa, and 30-60 keratan sulfate side chains, each 5-15 kDa. Figure 5–31. Extracellular matrix of mouse endometrium after fixation in the presence of Safranin O. A network of proteoglycans fills the intercellular spaces. Some proteoglycan filaments are in close contact with the cell surface (arrows). Medium magnification. (Courtesy of C. Greca and T. Zorn.) (1) Glycosaminoglycanen (GAG) : lineare polyscacchariden (herhalende disaccharide eenheden b.v. glucosamine en glucuronic acid) 4 types GAG: > dermatan sulfaat > chondroitine sulfaat > keratan sulfaat > heparan sulfaat (2) Proteoglycanen = GAG gebonden aan een centraal eiwit (5-32) > 3-dimensionael structuur met een centrale proteïne 80 – 90 % koolhydraten => in staat tot het binden van cationen. De koolhydraten gedeeltes bevatten: hydroxyl, carboxyl, sulfaat groupen = hydrofiele polyanionen! Proteoglycanen zijn gehydrateerd en hebben een hoge viscositeit. Grote variatie aan proteoglycanen: > verschillende soorten core proteïnes > verschillend aantal GAGs > GAG met een verschillende lengte > GAG met een verschillende samenstelling Figure 5–32. The molecular structure of proteoglycans and glycoproteins. A: Proteoglycans contain a core of protein (vertical rod in drawing) to which molecules of glycosaminoglycans (GAGs) are covalently bound. A GAG is an unbranched polysaccharide made up of repeating disaccharides; one component is an amino sugar, and the other is uronic acid. Proteoglycans contain a greater amount of carbohydrate than do glycoproteins. B: Glycoproteins are globular protein molecules to which branched chains of monosaccharides are covalently attached. (Reproduced, with permission, from Junqueira LCU, Carneiro J: Biologia Celular e Molecular, 7a ed. Editora Guanabara Koogan. Rio de Janeiro, 2000.) 2 grote klassen proteoglycanen: 2.1- Cel-oppervlakte proteoglycanen : (5-33) > Het centrale proteïne overspant de plasma membraan > korte cytosol extensie (verbonden met het cytoskelet) > extracellulaire extensie met GAGs 2.2- extra-cellular matrix proteoglycanen > Niet specifiek gebonden op cel Proteoglycaan synthese: > proteïn synthese in het RER > glycolisatie start in het ER > sulfatering in het GC Figure 5–33. Schematic diagram of cell-surface synedcan proteoglycan. The core protein spans the plasma membrane through the cytoplasmic domain. The syndecan proteoglycans possess 3 heparan sulfate chains and sometimes chondroitin sulfate.  (3) Glycoproteïnen (Multiadhesive) = proteïne eenheid waaraan koolhydraten vast hangen > proteïn eenheid is het grootst vertakte polysacchariden Glycoproteïnen hebben een functie bij cel adhesie: (5-32) > bv. Fibronectine: binding sites voor (5-34) > cellen > collageen > GAGs >> betrokken bij cel adhesie en migratie > bv. Laminine: adhesie van epitheliale cellen aan de basale lamina De cellen bevatten matrix receptoren (integrines) die binden op: > collageen, > fibronectine > laminine Figure 5–32. The molecular structure of proteoglycans and glycoproteins. A: Proteoglycans contain a core of protein (vertical rod in drawing) to which molecules of glycosaminoglycans (GAGs) are covalently bound. A GAG is an unbranched polysaccharide made up of repeating disaccharides; one component is an amino sugar, and the other is uronic acid. Proteoglycans contain a greater amount of carbohydrate than do glycoproteins. B: Glycoproteins are globular protein molecules to which branched chains of monosaccharides are covalently attached. (Reproduced, with permission, from Junqueira LCU, Carneiro J: Biologia Celular e Molecular, 7a ed. Editora Guanabara Koogan. Rio de Janeiro, 2000.) Figure 5–34. A: The structure of fibronectin. Fibronectin is a dimer bound by S—S groups, formed by serially disposed coiled sites, that bind to type I collagen, heparan sulfate, other proteoglycans, and cell membrane receptors. B: The structure of laminin, which is formed by 3 intertwined polypeptides in the shape of a cross. The figure shows sites on the molecule with a high affinity for cell membrane receptors and type IV collagen and heparan sulfate, which are components of basal laminae. Laminin thus promotes adhesion of cells to basal laminae. (Reproduced, with permission, from Junqueira LCU, Carneiro J: Biologia Celular e Molecular, 7a ed. Editora Guanabara Koogan. Rio de Janeiro, 2000.) Figure 5–35. Transverse section of mouse endometrium. Immunocytochemical staining shows the distribution of fibronectin in the endometrial stroma. Medium magnification. (Courtesy of D. Tenório and T. Zorn.) Figure 5–36. Transverse section of tongue. Immunocytochemical staining shows the distribution of laminin basement membranes in epithelial layer, capillary blood vessels, nerve fibers, and striated muscle. Medium magnification. Op de Cel: Integrines (met matrix receptoren) zijn transmembranaire linker proteïnes > Binden met hun ligand in de extracellulaire matrix > zwakke affiniteit tussen integrines en ligand > Verkennen van de omgeving! Integrines interageren met het cytoskelet (actine microfilamenten).(5-37). Figure 5–37. Integrin cell-surface matrix receptor. By binding to a matrix protein and to the actin cytoskeleton (via alphaactinin) inside the cell, the integrin serves as a transmembrane link. The molecule is a heterodimer, with alpha and beta chains. The head portion may protrude some 20 nm from the surface of the cell membrane into the extracellular matrix. SOORTEN BINDWEEFSEL Alle types BW bevatten vezels, cellen en grondsubstantie (5-40) BW in engere zin (5-41) (5-42) (5-43) (5-44) (1) Losmazig: opvullen van ruimtes, ondersteuning van epitheliale weefsels, lagen rond lymfatische en bloed vaten (2) Dens (straf): weerstand en bescherming Weining cellen Dominatie van collagene vezels (2.1.) Straf ongeordend: > geen duidelijke oriëntatie > 3-dimensioneel network >resistent aan stress uit alle richtingen (2.2.) Straf geordend: (5-45) (5-46) (5-47) > lineare orientatie (pezen) > parallel dicht opeengepakte bundels collageen > weining intercellulaire grondsubstantie > fibrocyten: >> kern parallel met de vezels >>weining cytoplasmatische plooien Figure 5–40. Simplified scheme classifying the principal types of connective tissue, which are discussed in the chapters indicated. Figure 5–41. Section of rat skin in the process of repair of a lesion. The subepithelial connective tissue (dermis) is loose connective tissue formed soon after the lesion occurs. In this area, the cells, most of which are fibroblasts, are abundant. The deepest part of the dermis consists of dense irregular connective tissue, which contains many randomly oriented thick collagen fibers, scarce ground substance, and few cells. H&E stain. Medium magnification. Figure 5–42. Section of loose connective tissue. Many fibroblast nuclei are interspersed with irregularly distributed collagen fibers. Small blood vessels are indicated by arrows. H&E stain. Medium magnification. Figure 5–43. Section of immature dense irregular collagen tissue. This figure shows numerous fibroblasts (arrow) with many thin cytoplasmic extensions (arrowheads). As these cells are pressed by collagen fibers, the appearance of their cytoplasm depends on the section orientation; when the section is parallel to the cell surface, parts of the cytoplasm are visible. PT stain. Medium magnification. Figure 5–44. Dense irregular connective tissue contains many randomly oriented bundles of collagen fibers. H&E stain. Medium magnification. Figure 5–45. Longitudinal section of dense regular connective tissue (tendon). Bundles of collagen fibers fill the spaces between the elongated fibroblasts. H&E stain. Medium magnification. Figure 5–46. Longitudinal section of dense regular connective tissue from a tendon. A: Thick bundles of parallel collagen fibers fill the intercellular spaces between fibroblasts. Low magnification. B: Higher magnification view of a tendon of a young animal. Note active fibroblasts with prominent Golgi regions and dark cytoplasm rich in RNA. PT stain. Figure 5–47. Electron micrograph of a fibrocyte in dense regular connective tissue. The sparse cytoplasm of the fibrocytes is divided into numerous thin cytoplasmic processes that interdigitate among the collagen fibers. x25,000. Een peesschede bestaat uit 2 lagen platte cellen die een visceuze vloeistof produceren (vergelijkbaar met het synoviaal vocht in gewrichten) – water – proteinen – GAGs – glycoproteinen – ionen Smeermiddel die zorgt voor een beweegbaarheid van de pees in de peesschede Dit systeem wordt verstoord bij peesschede ontsteking Loose connective tissue and dense irregular connective tissue. Examples of these connective tissue types shown here indicate the close association that often occurs between these two types. (a)Loose connective tissue (L) of a gland contains faintly stained ground substance with fine fibers of collagen and frequently forms a thin layer near epithelia, while dense irregular connective tissue (D) forms a thicker layer and is invariably much richer in larger bundles of collagen. Scattered leukocytes can be seen in both connective tissues, along with the large irregular spaces of lymphatic vessels (left). (X100; H&E) (b)Trichrome staining of a section from skin demonstrates the blue staining of collagen with this method and its relative density in loose (L) and dense irregular (D) connective tissue. (X100; Mallory trichrome) (c)Another example of dense irregular connective tissue, showing the randomly arranged large collagen bundles. The arrangement of collagen strengthens the tissues and resists tearing from all directions. (X150; H&E) (d)Dense irregular connective tissue (D) forms a thick, protective capsule around many organs such as the testis shown here. Here the