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Connective tissue proper There are three major components of connective fibers, ground substance and cells. According to connective tissue ground substance divide into: 1- connective tissue proper ( soft matrix ) a- embryonic C. T b- matrix c- fibro cartilage 2- cartilage ( rubbery): a- hyaline b- elastic 3- bone ( solid) permanent cells of the connective tissue = fixed cells 1- fibroblast it is flat, branched multiple processes thin nuclei oval - flat widely distributed in the connective tissue found in between the bundle of collagen fibers EM : They have achromatic nuclei, rich r ER ribosome's and a prominent GA They are responsible for the synthesis of collagen, elastic and reticular fibers and the ground substance it is highly motile and proliferative cells Mesenchymal cells: fibrocytes or perivascular cells or undifferentiated mesenchymal Site: They present near the blood vessels, they are directly continuous with basal lamia of blood capillary They have satellite shape oval nucleus It They are not highly differentiated cells. They retain the multiple potentials of embryonic mesenchymal cells. They can develop into other adult cells under certain conditions such as adipose cells, mast, smooth muscle, fibroblast. Adipose or fat cells Site: They are predominate in adipose C.T, present their in groups. They may present single in other types of C.T. They are large cells in the oval and peripherally located nucleus They synthesize + accumulate "store" fat in their cytoplasm If they store fat or lipid as a single large lipid droplet unilocular adipose cell The unilocular adipose cell is essential for energy storage They composes the with adipose tissue of humans. Adipose cell process receptors for hormone glycogen, ATCH which are lipolytic (breakdown of lipid) Hypertrophic growth i.e. increase in the size and number of adipocytes . later in life only size four times is affected. Loss of adipose tissue was ( as a reduction in calories) is due to reduction of fat cell size with no reduction in cell number. In some area ( kidney, feet, hand, around eyes) adipose tissue not depicted ( only in sever case of starvation) . Multilocular adipose tissue: brown fat Site: some mammals particularly these that hibernate in ferns + neonate ( of human ) Brown fat cell are unique in their abundance of mitochondria Have high ability to store fat and generated rapidly Their thermogenic properties are induced by noradrilanin and sympathetic innervations They allow rapid distribution of heat throughout the body -Atlas of hist. (di Fiore’s) -Atlas of hist. (di Fiore’s) Transient cells of C.T They are cells that migrate from the blood to the C. T tissue under certain condition « They originate from granulocytes, monocytes and lymphocytes . They include: eosinophils, neutrophils, basohils, moncytes, plasma cells NB: mast cells, plasma cells, Macrophages = they are present in C.T and do not normally occur in blood such I-Mast cells" other name largest" : C. T basophils ( originate from haematopioteic cells) They are related to but net identical to blood basophilia They are close to the blood vessels They mast cell are large ovoid cell with a spherical nucleus They contain large ( metachromatic) basophilic granules They posses large rER, GA, mitochondria EM : posses different size & form The substances that release by granules of the mast cell include: 1- Histamine ( vasodilator, permeability of the blood vessels 2- Heparin ( anticoagulant) 3- Leukotrienes (past= sbwractin substancey anaphylaxis ) SRS-A 4- Esenophil ehemotactic factors 5-Platcpct activating factor. 6- Prostaglandin cause bone spasm. 1+ 3 permeability of blood vessels localized edema. Mast cells and basophils posses receptors for IgE at the Fc domain called Fc receptors. When antigen + antibody interaction occur Localized or sever reaction anaphylactic shock. release mediator Site They are numerous in the area that have direct contract with the outside environment (lining of D.T, R.T, dermis). 2. Lymphocytes They are numerous in subepithelial C.T (lamina propria) especially of R.S. gastrointestinal. They occur in the sites of chronic inflammation and viral infection. They are motile. They are responsible of cell mediated immunity properties (see blood). 3. Plasma cells = They are antibody producing cell derived from B lymphocytes. They are responsible for humoral immunity. They have eccentric nucleus and intense cytoplasmic basophilia. The nucleus has a characteristic " wheel spoke" "cartwheel" "clock face" chromatin pattern. They are not motile and have a short life of 10 -30 days. EM : Extension rER, prominent GA to produce protein immunoglobulin. They have heterochromatine nucleus. This explained that each plasma cell is responsible for formation of only one protein, a specific antibody. Therefore only a small segment of genius must be exposed for transcription not the whole nucleus as in protein synthesis cells (i.e. fibroblast) 1- Macrophages = tissue histocytes - Highly motile, phagocytic, long lived cell. They are derived from monocytes of the blood. They have irregular shape cell bodies cell membrane thrown into folds pseudopodia They have acidophilic cytoplasm with numerous lysosomes vacuoles & residual bodies. -Atlas of hist. (di Fiore’s) They have indented kidney shaped nucleus. Lysosomes numerous fold or finger like projection of the cell membrane & cytoplasm are the structures indicative of the phagocytic capability of the cell. Macrophage function is phagocytosis of either bacteria or virus cell debris. Also they play a role in immune reaction by presenting lymphocytes with concentrated antigen derived from phagocytosed foreign cells or protein. They also produce immuno regulatory substances such interleukin 1 which enhance lymphocyte proliferation. Sometime when macrophage encounter large foreign bodies, they fuse to form large cell with up to 100 nuclei that engulfs the foreign body. These multinucleated cells are called foreign body giant cells. Some macrophages have specific fc + C3 (complement 3 ) receptors on their surface to bind with opsonins (IgA + IgM ) and C3. This will attract specific bacteria or foreign body to attach to antibodies A – Ab interactions promote or enhance the function of phagocytosis. Also macrophages may posses receptors for fibronection (non specific opsonins). This has a high affinity for damaged tissue attract macrophages to phagocytize damaged cells + extra cellular matrix. Macrophages produces immunoregulatory substances (interleukin 1), lysosomal hydrolase, neutral proteinases (such as plasminogen, activator, collagenas, elastase), arginase, antimicrobial lysozyme. Protein of the complement system Antiviral interferon. Growth factor and mitogenic protein. Endogenous pyrogen important mediator of fever. Prostaglandin Leukotrienes mediator of inflammation. H2o2 destruction of microbes. Connective tissue fibers Include collagen, elastic and reticular fibers. 1. Collagen fibers They are present in colorless wavy bundles. These bundles formed of non – branching small fibrils run parallel to each other. The bundle can branched or anastomosed with adjacent bundles. They resist tensile forces. Collagen fibers formed of a protein polymer called collagen, which formed of monomeric units called tropocollagen. Tropocollagen units are arranged in parallel overlapped quarter length with 280 nm long and 5 nm wide. This yield cross by quarter length striation repeated after 67 nm. Bundle fiber fibril myofibril show cross striation. They are found in the most of C.T. but vary in abundance. Collagen fiber destroyed by boiling or chemical treatment and transformed into gelatin. But gentle treatment (by neutral salt or weak acid solution) gives rise to free tropocollagen units. LM Fiber of collagen stained light pink H & E. Stained pink with van ginsen. Stained brown with silver. Formation of collagen fiber There are some events occur inside the fibroblast and other events occur on the surface of fibroblast. Cellular events uptake of amino acids need for formation of procollagen (precursor of collagen molecules) hydroxylation of protein chain formation of procollagen triple helix molecule packaging of procollagen in rER by golgi into secretory vesicles Exocytosis. Extracellular events = transformation of procollagen to tropocollagen polymerization of tropocollagen into collagen fibril. Thus = tropocollagen molecule is composed of 3 alpha units chain arrange in helical configuration. They are rich in glycin & proline. Vit. C is needed a cofactor for enzymatic conversion of proline to hydroxyproline and lysine to hydroxylysine. Vit C deficiency result in scurvy, because hydroxyproline is involved in hydrogen bonding between polypeptide chain. Hydroxylysine is involved in cross linking of tropocollage into bundles of collagen. Tropocollagen can be produce by fibroblast, chondroblast, osteoblast and smooth muscle cell. Types of collagen There are at least five molecular types of collagen (actually 9). The differences occur in amino acid composition of alpha chain. Type I: Most abundant + widespread collagen (all tissue) 90% of body collagen. Type II: Found in cartilage and some tissues of the eye. Type III: Skin, cardiovascular, uterus, alimentary tract, endoneurum, lung. Type IV: Basal lamina of epithelia + endothelial cells, glomeruli, it lacks periodicity. Type V: Adult C.T stroma, fetal membrane, placenta. 6 – 9: 6,8 not determined in function 7 basal lamina 9 cartilage. Function Provide resistance to force, tension and strech. Give structural support and elasticity. Play an important role in the selective permeability of the basment membrane. 2. Reticular fibers They are thin collagen fibers arranged in delicate networks instead of bundles. They stained by silver method. They branch and anastomose to form a network to support individual cells and organs. Collagen and reticular are very similar in chemical composition. Supportive to lymphoid organ a hemopoietic organs. 3. Elastic fibers They stretch easily but not strong as collagen. Appear yellow in fresh state. They are composed of protein called elastin. Site: They are present in tissues that require flexibility such as large arteries, trachea, framework of the spleen . The skin, intervertebral ligament (ligamentum flava) Their thickness, length, arrangement differ according to the site in large artery , they arrang in thick fenestrated lamellae. Elastic fibers are usually less than 1 Mm in diameter. They exhibit no periodicity. They are rich in glycin, prolin and inaddition (rather than collagen) valine, desmosine and isodesmosine. Ground substance of the connective tissue It is the component that occupies the space between the cells and fibers. In life, its viscous, clear substance that has slippery feel. It is composed of water, salt and glycosaminoglycan which provide its viscosity (most common: hyaluronic acid) which appears homogenous and transparent when stained with H&E. Other types of glycosaminoglycans are sulfated group: Sulfated proteoglycans. Chondrotin sulfate, dermatan sulfate, keratan sulfate, heparan sulfate. Ground substance provide x structural support Provide a medium for diffusion of nutritients & gases. Act as physical barrier to prevent spread of large particles especially bacteria (some bacteria produce hyaluronidase to promote their invasiveness). Some structural proteins in ground substance have specific function. Fibronectin (cell matrix ligand) Promotes attachment of fibroblast and other C.T cells to collagen fibers. Plays a role in cellular processes such migration, differentiation, chemotaxis, phagocytosis. Laminin Chondronectin Associated with basment membrane provide attachment of epithelial cells to type IV collagen. Promotes attachment of cartilage cells to collagen