Connective tissue 1. Connective tissue – terminology and classification 2. Cells of the connective tissue 3. Extracellular matrix: V ground substance V protein fibers 4. Connective tissue proper: V loose connective tissue V dense connective tissue regular irregular 5. Mononuclear phagocyte system Terminology and peculiarities ° Textus connectivus: V cells of mesenchymal origin V extracellular matrix ° connective tissue features: V interior location – never found at the surface V cellular polymorphism V abundant amounts of extracellular matrix – determines the species diversity V absence of cell polarity V high adaptive and regenerative capabilities V metaplastic abilities V specialized structures: intracellular extracellular NB: most abundant of the basic tissues – ½ of the human body mass Prof. Dr. Nikolai Lazarov 2 Functions of connective tissue V binding together other tissues in the formation of organs – capsules V structural support (mechanical role) – bones, ligaments and tendons V nutritive role (homeostasis) – blood V defensive functions (barrier and immunologic – antibodies) Prof. Dr. Nikolai Lazarov 3 Cells of the connective tissue V productive and nutritive: synthesize and secrete the extracellular matrix regenerative and repair abilities V defense cells: motile and circulatory activity V pigment cells: presence of specialized structures Prof. Dr. Nikolai Lazarov 4 Productive and nutritive cells V Productive cells: fibroblasts, chondroblasts, osteoblasts, odontoblasts fibrocytes, chondrocytes, osteocytes V Undifferentiated mesenchymal cells – stem cells V Nutritive cells: lipocytes (adipocytes, fat cells) • unilocular • multilocular Prof. Dr. Nikolai Lazarov 5 Defense cells V macrophages (Gr. big eaters) – monocytic origin: fixed (histiocytes) tissue macrophages migrated macrophages dendritic cells V plasma cells (plasmocytes) – differentiation from B-lymphocytes produce antibodies (immunoglobulins) V mast cells (mastocytes, Gr. masto , I feed) – metachromasia: connective tissue mast cell – heparin, ECF-A, SRS-A mucosal – chondroitin sulfate primary and secondary mediators immediate hypersensitivity reactions – anaphylactic shock V blood cells: granulocytes • neutrophilic – microphages • eosinophilic • basophilic lymphocytes Prof. Dr. Nikolai Lazarov 6 Pigment cells V melanin-containing cells: melanocytes – dermis, choroidea, meninges melanophores – skin V chromatophores: chemosiderophores lipochromophores Prof. Dr. Nikolai Lazarov 7 Functions of connective tissue cells Prof. Dr. Nikolai Lazarov 8 Extracellular matrix ° Extracellular matrix: V amorphous substance (ground substance, tissue fluid) V connective tissue fibers – protein fibers – types: collagen fibers elastic fibers reticular fibers Prof. Dr. Nikolai Lazarov 9 Amorphous intercellular substance ° ground substance – the non-cellular component of the matrix: V viscous, gel-like V highly hydrated V transparent V colorless complex mixture ° molecular components: V glycosaminoglycans (acid mucopolysaccharides) V proteoglycans V structural glycoproteins ° tissue fluid Prof. Dr. Nikolai Lazarov 10 Ground substance ° glycosaminoglycans – long unbranched polysaccharides consisting of a repeating disaccharide unit: V non-sulfated – hyaluronic acid V sulfated: heparan sulfate chondroitin-4-sulfate chondroitin-6-sulfate dermatan sulfate keratan sulfate Prof. Dr. Nikolai Lazarov 11 Ground substance ° proteoglycans – glycoproteins that are heavily glycosylated: V a core protein V one or more covalently attached glycosaminoglycan(s) – 80-90%: heparan sulfate chondroitin-4-sulfate chondroitin-6-sulfate dermatan sulfate keratan sulfate ° extracellular matrix proteoglycans : V aggrecan V perlecan V decorin V biglycan ° cell-surface proteoglycans: V syndecan V fibroglycan V glypican Prof. Dr. Nikolai Lazarov 12 Ground substance ° multiadhesive glycoproteins – proteins that contain oligosaccharide chains (glycans) covalently attached to polypeptide side-chains: V a protein moiety – predominant V attached carbohydrate fibronectin (Lat. fibra, fiber + nexus, interconnection) chondronectin laminin Prof. Dr. Nikolai Lazarov 13 Tissue fluid ° tissue fluid – 10-12 l (60-70% of the matrix): V similar to blood plasma V contains: plasma proteins of low molecular weight ions and diffusible substances V hydrostatic and osmotic pressure edema Prof. Dr. Nikolai Lazarov 14 Protein fibers ° Connective tissue fibers: V collagen V elastic V reticular NB: in many cases, the predominant fiber type is responsible for conferring specific properties on the tissue! Prof. Dr. Nikolai Lazarov 15 Collagen fibers Gr. kolla, glue ° fibra collagenosa: V most abundant (30% of dry b.w.) V low elasticity – 5% V strength – sustain 500 kg/cm 2 V acidophilic collagen fibers – 1-20 µm thick V collagen fibrils – 0.1-0.5 µm in diameter V collagen microfibrils – 50-90 nm; 68 nm periodicity V collagen molecules – molecular mass 360000 Da ° collagen: tropocollagen – 280 nm/1.5 nm 3 subunit α-polypeptide chains – triple helix amino acid content: glycine (33.5%) proline (12%) hydroxyproline (10%) hydroxylysine Prof. Dr. Nikolai Lazarov 16 Collagen biosynthesis ° producing cells – fibroblasts, chondroblasts, osteoblasts etc. ° Steps of collagenogenesis: V intracellular synthesis – rough ER hydroxylation of prolyl and lysyl residues glycosylation of hydroxylysine pro-alpha chains procollagen molecule V secretion exocytosis V extracellular assembling: propeptide removal peptidases tropocollagen – telopeptides Prof. Dr. Nikolai Lazarov 17 Collagen types ° 28 types of collagen: Prof. Dr. Nikolai Lazarov NB: collagen = 25-30% of all proteins in the human body 18 Reticular fibers ° fibra reticulares: V extremely thin – diameter 0.2-2 µm V form a network (rete = network) V resistant to acids and trypsin V PAS-positive – carbohydrates V argyrophilic – selective affinity for silver salts (Gr. argyros , silver + philein, to love) V 68 nm periodicity V loosely packed thin (45 nm) fibrils V content: collagen type ІІІ • rich in cystine, poor of proline and hydroxyproline • 6-12% hexoses • glycoproteins • proteoglycans V build up the reticular tissue: framework of hemopoietic organs smooth muscles, endoneurium Prof. Dr. Nikolai Lazarov 19 Elastic fibers ° fibra elastica: V thinner – diameter 0.2-4 µm V highly resistant to tension – 150% V lower force of strain – sustain 20-30 kg/cm2 V resistant to boiling, acid and alkali extraction, digestion by proteases V selective staining – orcein, resorcin-fucsin V content: elastin (750 amino acids; 70 kDa) • glycine and proline • desmosine and isodesmosine (4 lysine residues) microfibrils – 10-12 nm • polar amino acids • absent OH-lysine and -proline • fibrillin ~5% • fibromoduline І and ІІ • 0.5-2% proteoglycans Prof. Dr. Nikolai Lazarov 20 Elastic fiber system ° producing cells – fibroblasts ° 3 types of fibers – stages of development: V oxytalan fibers – 10 nm (Gr. oxys, thin) fibrae zonulares of the eye dermis glycoprotein-containing microfibrils (fibrillin) V elaunin fibers (Gr. elaunem, to drive) around sweat glands, dermis aorta elastic cartilage secretion of proelastin V elastic fibers: centrally – elastin peripherally – microfibrils Prof. Dr. Nikolai Lazarov 21 Classification of connective tissue Prof. Dr. Nikolai Lazarov 22 Classification of connective tissue Prof. Dr. Nikolai Lazarov 23 Loose (areolar) connective tissue ° textus connectivus fibrosus laxus: V most widespread type of connective tissue V cells and extracellular matrix: V fibers: collagen elastic reticular V amorphous ground substance ° Cells – productive, nutritive and defense: V proper (fixed): fibroblasts and fibrocytes V free: macrophages (histiocytes) – phagocytosis plasma cells – unmature and mature (Russell bodies) mast cells leukocytes – granular and agranular melanocytes Prof. Dr. Nikolai Lazarov 24 Compact dense connective tissue ° textus connectivus fibrosus compactus: V widely distributed – resistant to stress V cells and extracellular matrix – collagen fibers ° Cells – relatively few: V fibroblasts and fibrocytes ° Types: V dense irregular connective tissue: sclera reticular layer of the dermis capsules of the organs V dense regular connective tissue: tendons ligaments parallel , closely packed bundles of collagen fibrocytes alar cells Prof. Dr. Nikolai Lazarov 25 Lamellar dense connective tissue ° textus connectivus fibrosus lamellaris: V widespread distribution – aponeuroses and fascia of the muscles, dura mater ° Cells – relatively few: V fibroblasts and fibrocytes ° Intercellular matrix: V numerous collagen fibers V lesser elastic fibers: layers lamellae Prof. Dr. Nikolai Lazarov 26 Reticuloendothelial system V Systema reticuloendothelialis s. macrophagorum – Aschoff, 1924 V Synonym: Reticulohistiocyte system Karl Albert Ludwig Aschoff (1866-1942) Prof. Dr. Nikolai Lazarov 27 Mononuclear phagocyte system V Mononuclear phagocyte system – Van Furth, 1969 Prof. Dr. Nikolai Lazarov 28 Mononuclear phagocyte system V Reticuloendothelial System (RES) Ludwig Aschoff , 1924 V Reticulohistiocyte System (RHS) V Mononuclear Phagocyte System (MPS) Ralph Van Furth , 1969 1866-1942 Prof. Dr. Nikolai Lazarov 29 Thank you ... to be continued ... Prof. Dr. Nikolai Lazarov 30.