Histology 6 - Connective Tissues PDF

Differences between connective tissues and epithelia cells —> organisation of the cells (sparse cells in connective tissues), junctions (there aren’t junctions in connective tissues), extracellular matrix (a lot in connective tissue and almost none in epithelia cells) Connective tissues comprises a...

Differences between connective tissues and epithelia cells —> organisation of the cells (sparse cells in connective tissues), junctions (there aren’t junctions in connective tissues), extracellular matrix (a lot in connective tissue and almost none in epithelia cells) Connective tissues comprises a diverse group of cells within an extracellular matrix. The role of connective tissues is that of connecting and supporting other tissues. The connective tissues are made of cells and an abundant extra-cellular matrix (ECM). Almost all connective tissues come from the mesoderm Classification: Embryonic —> mesenchyme, mucous Connective tissue proper —> loose and dense Supportive connective tissue —> cartilage, bone Liquid connective tissue —> blood and lymphatic ECM is composed by: Protein fibers —> collagen fibers, reticular fibers and elastic fibers Ground substance —> jelly water based substance in which the proteins can be found Different connective tissues have different ratios of protein fibers and ground substance (es: blood has more ground substance as it is more fluid) Functions of ECM Provide mechanical and structural support to tissues Connects all the elements anchoring and supporting the body and its organs Transport of metabolites and other molecules Repair of injuries (via cell proliferation and fibers formation) Cell differentiation, activation and localisation All the components of the ECM are organised and have a defined role Three types of protein fibers in the ECM —> collagen, reticular and elastic. These proteins are released by cells (mostly fibroblasts) Fibroblasts —> principal cells producing collagen —> however in some tissues collagen is synthesised by osteoblasts, chondrocytes and pericytes Collagen types I - skin, bond, tendon, cornea II - cartilage III - reticular fibers, loose c.t., blood vessel walls, dermis  IV - basal lamina of epithelium and kidney glomeruli COLLAGEN FIBERS They are long, flexible non-branched fibers made of collagen —> they don’t extend much but they are highly resistant to mechanical stress (tendons, bone, cartilage and skin) Collagen is made of 3 procollagen chains together without the procollagen at the end Collagen I is made of 2 alpha chains and 1 beta mm chain The synthesis of collagen happens in the RER of fibroblasts —> folded pro-collagen molecules pass to the Golgi apparatus where fibrils assemble. Then covalent cross-links are made Collagen fibers —> Sequence of closely spaced transverse bands that repeat every 68nm along the length of the fibril coeeagenatTEN Collagen turnover —> collagen keeps being synthesised by fibroblasts and degraded by MMPs phagocytes —> this is because the ECM needs to be continuously renovated. With aging the turnover process slows down and it is harder to keep a renovated ECM The enzymes degrading ECM components are the metalloproteinases. TIMPs are inhibitors of MMPs (to regulate the degradation). MMPs are responsible for wounds healing and for some pathological conditions such as atherosclerosis. RETICULAR FIBERS Less abundant than the collagen fibers —> they are small branched fibers filling spaces and providing thin stroma of organs. They are made of COLLAGEN TYPE III comparison Collagen fibers are tightly packed, linear and made of different types of collagen while reticular fibers are only made of collagen III, they are sparse and arranged three- dimensionally They form the supportive stroma and basal lamina of epithelia, they are most common in liver, spleen and lymph nodes The prevalence of reticular fibers is also an indicator of tissue immaturity —> initial stages of wound healings (provide mechanical strength to newly synthesised ECM). They are gradually replaced by stronger type I collagen CLINICAL DROP: Osteogenesis imperfecta —> bones and ligaments are not well formed because the collagen is not perfectly assembled. It is caused by a gene mutation causing a defect in collagen synthesis ELASTIC FIBERS They are resistant to stress and they are made of elastin and fibrillin (no collagen). They are branched and respond to stretch and distension Elastic fibers are produced by fibroblasts and vascular smooth muscle cells, they are elastic, they are formed by two components (amorphous + microfibrillary) Amorphous component —> central core, elastin (synthesised as tropoelastin) Microfibrillary component —> surrounds the central core, fibrillin (filamentous protein polymerised in microfibrils). Aggregation happens in the extracellular environment CLINICAL DROP: Marfan syndrome —> non proper development of some sites of the body (skeletal, ocular and cardiovascular defects) caused by a deficiency of elastin-associated microfibrils GROUND SUBSTANCE Composed mainly by water and electrolytes + specialised molecules The ground substance is made of two families of molecules —> 1. Proteoglycans (core proteins and glycosaminoglycans) 2. Multiadhesive glycoproteins (Fibronectin and Laminin) Proteoglycans (or mucopolysaccharides)—> very large molecules composed of a core protein and glycosaminoglycans (GAGs) Different types of proteoglycans depending on the GAGs disaccharides used The molecules of water interact with the GAGs (negative charge) GAGs —> long polysaccharides containing repeating disaccharides units. GAGs: Hyaluronic acid Heparin Keratin Sulfate Heparin sulfate Chondroitin sulfate Dermatan sulfate Hyaluronic acid is a huge GAG and it cannot bind to the protein core —> it interacts with proteoglycans. The complex is called “proteoglycan aggregate” and it functions as a shock absorber (presence of water). Lysosomal storage diseases consist of malfunctions of lysosomes due to mutations which lead to an accumulation of glycosaminoglycans in the cell and in the ECM which affects the whole body Ground substance also contains multi adhesive glycoproteins (such as Fibronectin, Laminin and Osteopontin). Glycoproteins are more proteins than carbs while proteoglycans are more carbs than protein Fibronectin —> links cells to several components of the ECM, it is recognised by cells as a ligand for cell surface adhesive receptors, it is responsible for cell adhesion and involved in cell migration Fibronectin binding to integrin receptors induces reorganisation of actin micro filaments and cell adhesion Laminin —> binds to components of the ECM (collagen) and binds cell surface adhesive receptors (integrin family). Laminin interacts with receptors to allow the recognition of the Cells basement membrane Osteopontin —> present in the ECM of the bone, it attaches osteoclasts to the bone surface and it plays a role in calcium sequestration in the bone CELLS OF THE CONNECTIVE TISSUE —> 1. Resident cells (fibroblasts, adipocytes, mast cells, pericytes and macrophages) 2. Transient cells (monocytes, neutrophils, eosinophils, lymphocytes and plasma cells) RESIDENT CELLS Fibroblasts —> principal cells of the connective tissue, they are responsible for the synthesis of collagen, elastic fibers, reticular fibers and the carbohydrates of the ECM. They contribute to the homeostasis of the connective tissue.  nucleisqueezed in betweencollagen Myofibroblasts are cells closely related to fibroblasts and they are characterised by the presence of actin filaments of the α-smooth muscle actin (α-SMA). They are present in damaged tissues and are important during wound healing. They are linked to some pathological conditions (like fibrosis and tumour). They are even more active than normal fibroblasts. A normal fibroblast DOES NOT express α-SMA. Scars are a result of the overproduction of fibers by the myofibroblasts (so at a certain point they have to be turned back into fibroblasts to avoid excess tissue to be synthesised). Myofibroblasts sense the environment and get activated as a consequence. They have a really high mechanosensitivity. Macrophages —> they are phagocytise cells that derive from embryonic precursors (which develop during the embryonal phase and then stay there for the whole life) and circulating monocytes (which are attracted by a tissue and then differentiate into macrophages). They are immune cells but stay in the tissues. Macrophages eat debris, destroy pathogens and degrade aged elements of the ECM. They are 10-30 μm in diameter, they have a stellate shape, a kidney-shaped nucleus and abundant lysosomes. They are increased during inflammation and they live up to 2-3 months (low rates of proliferation) Defense function —> phagocytosis + antigen presentation + secretion of cytokines and enzymes Macrophages acquire different morphologies and functions depending on the tissues Lungs —> alveolar macrophages Brain —> microglia Liver —> Kupffer macrophages Kidney —> glomerulus macrophages Macrophages are plastic cells —> A macrophage can acquire different functions depending on what it interacts with (stimuli). It can acquire tumoural functions or anti inflammatory functions shape adifferent stimuli of because different Adipocytes (or fat cells) —> the nucleus and the cytoplasm are stored laterally below the plasma membrane due to a continuous accumulation of lipids Adipocytes don’t proliferate, the total number is determined in the newborn during the first months of life (then new ones can only be made from stem cells) Mast cells —> they originate as immune cells and then enter the connective tissue (where they differentiate into mast cells). The cytoplasm is rich of granules containing mediators of inflammation (histamine, heparin…). They try to increase the permeability of blood vessels to let the immune response arrive. They are around 20-30μm and they have IgE receptors to mediate the inflammatory process —> immediate hypersensitivity reactions to allergens TRANSIENT CELLS (they occasionally go in the connective tissue but are not fixed there) Leukocytes —> they exit the bloodstream and move in the connective tissue by crossing the walls of small veins and capillaries. Their number increases during inflammation. The cells are in the blood and to go the connective tissue they have to pass the epithelial cells of the blood vessel. To do this they squeeze between two cells. rousoutheenaothelie or Diapedesis araesion morewees receptor chemoetrectons Diapedesis —> finger-like protrusion or pseudopodium that penetrates between two endothelial cells