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The Connective Tissue M. Soleimani , Ph.D

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The Connective Tissue M. Soleimani , Ph.D Connective tissue Connective tissue functions:
Establishing a structural framework Protecting delicate organs Supporting, surrounding and interconnecting tissues Transporting fluids and dissolved materials Storing energy reserves Defending the body from microorganisms Connective Tissue Classification
Embryonic Connective Tissue Connective Tissue Proper Loose Mesenchymal Dense irregular Dense Dense regular Mucous Reticular Adipose A Classification of Connective Tissues Connective Tissue Connective Tissue Composition
Fibers (collagen, elastic, reticular) Cells (fibroblasts, immune, vascular) Ground substance (glycosaminoglycans, proteoglycans, glycoproteins) Connective tissues contain
Specialized cells Matrix Composed of extracellular protein fibers and a ground substance CELLS OF AREOLAR LOOSE CONNECTIVE TISSUE
Resident Immigrant Fibroblast Lymphocyte Myofibroblast Neutrophil *Adipose Cell Eosinophil Plasma Cell Basophil Mast Cell Monocyte Macrophage *not motileRed :derived from immigrant cells Connective Tissue Cells
Fixed cells: Mesenchymal cells Fibroblasts Macrophages Mast cells Adipose cells Pericytes Transient cells: WBC of Blood Plasma cells FIBROBLAST Derived from fibroblast mitosis and also from primitive mesenchymal precursor cell differentiation Secretes collagen, all elastic fiber components,hyaluronic acid , proteoglycans etc. (i.e. most of the extracellular matrix) fibroblast ---structure: LM:
large,flattened cell with processes- stellate in shaped Large ovoid pale nucleus-contain more fine chromatin, with clear one-two nucleoli Weakly basophilic cytoplasm-homogeneous EM: rich in RER,Golgi appatatus and free ribosome ---function: synthesize fibers and ground substance Fibroblast Fibroblast Fibroblast *fibrocyte: still state or inactive fibroblast
---structure: spindle-shaped, small N:small,dark stained Acidophilic cytoplasma EM:less organelles ---function: become into fibroblast for repairing Macrophage, a long-lived defense cell
Derived from monocyte Functions: Phagocytosis Pinocytosis Bacterial killing Viruses only sometimes killed by macrophage but usually they stimulate macrophage to secrete lymphocye activators (e.g. interferons) that result in viral destruction but macrophages can become viral reservoirs (e.g. HIV) Antigen-presenting cell (i.e process & present to lymphocytes to stimulate lymphocyte function) Macrophage Phagocytosis of cell debris and microorganisms
Presenting antigens to lymphocytes RBC turnover in spleen Two categories: Resident and Elicited Foreign body giant cells in response to excessively large materials form from many macrophages macrophage ---structure: LM:
round or ovoid-irregular in shape when it have short blunt processes_pseudopodium Small and dark nucleus Acidophilic cytoplasm EM: rich in a. lysosome b. Phagosome phagocytosis and
pinosome pinocytosis c.Remnant d.Microfilament and microtubule Macrophage ---function: a.Chemotaxis: chemotactic factor b. phagocytosis: Special phagocytosis: recognize Bacterium, virus and foreign cell non special: carbon particles, dust and dead cells *Phagosome(pinosome) + primary lysosome secondary lysosome remnants c.secretion: lysozyme, complement and interleukin-I (IL-1)and interferon(INF)
b. antigen presenting function: *capture antigenprocesses+ MHC II molecule (major histocompatibility complex molecules)antigen-MHC II complexesTLC Micro Vacuum Cleaner! Macrophage vs Ecoli PLASMA CELLS Not normallyfound in plasma Derived from Type B lymphocytes that enter connective tissue Synthesize and secrete by exocytosis specific antibodies (immunoglobulins) that bind to specific antigens (i.e. the moleculesthat provoked the plasma cell formation from B lymphocyte) Antigen/antibody complex stimulate destruction of antigen (e.g. by stimulating phagocytosis or lysis of foreign cell source of that antigen) Some plasma cells may be exception to definition of resident cell as being long-lived since some only live 2 weeks but evidently plasma cells can also live longer Plasma Cell Differentiate from B - lymphocytes
Oval cell with basophilic cytoplasm, pale centrosome, clockface nucleus plasma cell ---structure: LM: round or ovoid Round eccentrically-located nucleus with more spot-liked heterochromatin Basophilic cytoplasm Plasma Cell Plasma Cell EM:rich in parallelly arranged RER, free ribosome and Golgi complex ---function: synthesize and secrete immunoglobulin, Ig-antibody Plasma Cell MAST CELLS Secretory cells rich in large secrtory granules Derived from bone marrow precursors Synthesize and secrete by exocytosis a variety of substances stored in large secretory granules Involved in inflammatory response Secrete (in response to IgE) Histamine (blood vessel permiablilty, smooth muscle constriction); heparin; proteases; chemotactic factor for eosinophils. Mast Cell mast cell ---structure: LM: round and large cell Small dark-stained nucleus Basophilic secreting granules Mast Cell Basophilic secreting granules:
heparin:an anticoagulant Histamine: cause cap. permeability, cap. leakage to form oedema and contraction of SM Eosinophil chemotactic factor Cytoplasm contain: leukotriene- slow reaction substance ---function: cause allergic reaction Mast Cell fat cell ---structure: large, round or polygonal flattened ovoid nucleus located on one side of cell thin layer of cytoplasm a large lipid droplet ---function: synthesize and store fat undifferentiated mesenchymal cell
---structure:similar to fibrocyto ---function:multidifferentiating potential leukocytes: neutrophil,acidophil and lymphocyte Mesenchymal cell The Extracellular Matrix
Structural Proteins collagens elastins Cell Binding Proteins Laminins Fibronectins Glycosaminoglycans (GAGs). Hyaluronans Chondroitin sulfates Heparan sulfates (including heparin) Keratan sulfates. Proteoglycans. GAGs bind to core proteins. e.g. aggrecan in cartilage. Fibers Collagens 25% (by mass) of all protein in the body At least 25 types
19 (Types arranged in 7 broad classes: Fibril-Forming Collagens w/ striated macrofibers: I, II, III, V, XI Network-Forming Collagens: IV, VIII, X Fibril-associated with interrupted triple helixes: IX, XII, XIV, XVI, XIX Beaded Filament-Forming Collagen: VI Collagen of Anchoring Fibrils: VII Collagens with a Transmembrane Domain: XIII, XVII Collagen Types XV and XVIII At Least 33 Different Gene Products, arranged as Homo- or Hetero-trimers Common structural elements: collagen helix Rich in (hydroxy)proline and (hydroxy)lysine glycine at every 3rd residue trimer in native structure How is collagen made? STEP 1: Synthesis of -chains of pre-procollagen on ribosomes and endoplasmic reticulum How is collagen made? STEP 2: Hydroxylation of proline residues to obtain hydroxyproline (an aminoacid unique to collagen). a reaction that substitutes a hydroxyl group, OH, for a hydrogen atom, H, in the proline the hydroxylation reaction secures the chains in the triple helix of collagen hydroxylation is catalyzed by the enzyme prolyl-4-hydroxylase Vitamin C is essential for enzyme action, scurvy! OH OH Alpha-chain OH How is collagen made? STEP 3: Hydroxylation of lysine residues to obtain hydroxylysine hydroxylysine is needed to permit the cross-linking of the triple helices into the fibers the enzyme peptidyl proline hydroxylase is essential OH OH OH Alpha-chain OH OH How is collagen made? STEP 4: Glycosylation of some hydroxlysine residues glucose and galactose are added by enzymes galactosyl transferase and glycosyl transferase may affect fibril size OH OH OH Alpha-chain OH OH Gal Glu How is collagen made? STEP 5: Assembly of the three alpha chains to from procollagen formation of disulphide bonds between parts of the polypeptide chains known as registration peptides at the C-terminal three chains associate, align and the triple helix forms in a zipper-fashion giving procollagen C-Terminal N-Terminal s Gly is crucial for forming collagen structure. EXTRACELLULAR SPACE N-terminal protease
STEP 6: Secretion of procollagen molecules by exocytosis into the extra cellular spaceSTEP 7: Cleavage of registration peptides in the extra cellular space, by procollagen peptidases. The resulting molecule is collagen (finally!) EXTRACELLULAR SPACE N-terminal protease Assembly of collagen fibers begins in the ER and is completed outside the cell
Hydroxylation of Pro & Lys glycoslyation of Lys Cleavage of C and N terminal propeptides makes collagen 1000x less soluble => Impt this occurs OUTSIDE of cell The basic structural unit of collagen is a triple helix
Fibrils stabilized by novel Collagen and elastin Pro/Lys X-links that are specific for these proteins Collagen fibrils form by lateral interactions of triple helices How is collagen made? STEP 8: Self-assembly or polymerization of collagen molecules form collagen fibrils. STEP 9: Cross-linkage between adjacent collagen molecules that stabilizes the fibrils. = collagen molecule Collagens form diverse structures
Types VI and IX are Fibril-Associated Collagens Collagen Synthesis collagenous fiber(white fiber)
LM: 1-20 um in diameter Belt-liked wave and branch to form a network Eosinophilic EM: parallel-arranged fibrils
20-200nm in diameter Have periodic cross striation at 64nm interval Collagen Fibroblast surrounded by collagen fibrils in the connective tissue of embryonic chick skin ELASTIC FIBERS Composed of: Elastin microfibrillar proteins (including fibrillin) Components made by: Fibroblasts In blood vessels most by smooth muscle In other tissues by cells of mesenchymal origin such as chondroblasts Elastin precursor secreted: Tropoelastin Function: Confers elasticity (allows recoil after stretching e.g.important in blood vessels) elastic fiber (yellow fiber)
LM: thinner and less, um Slight red(HE), purple(aldehyde fuchsin) or brown(orcein) Branch and form a network EM: core: elastin-low electron density Peripheral: microfibril nm, electron dense fibrillin reticular fiber LM: thin and less,0.2-1.0 um in diameter
Branch to form network Argyrophilic fiber(silver impregnation method) EM: type III collagen 64nm cross striation ---distribution: reticular tissue connecting portion, e.g.reticular lamina Extracellular matrix proteoglycans
Hyaluronan resists compression and facilitates cell migration Cell-surface proteoglycans-The Syndecan Family of Single TM proteins Many growth factors are sequestered and presented to cells by proteoglycans glycoprotein: proteins
---fibronectin cellsfibronectincollagen proteoglycan ---laminin ---chondronectin ---function: Connection affect the differentiation and movement of cells Structure of Laminin Trimer (~850 kD total MW) tissue fluid tissue artery Tissue fluid vein blood steam dehydration oedema Connective tissue proper
Classified as loose or dense Loose Embryonic mesenchyme, mucous connective tissues Areolar tissue Adipose tissue Reticular tissue Dense Dense regular CT Dense irregular CT The Cells and Fibers of Connective Tissue Proper Loose Connective Tissue Areolar 400X
collagen nuclei of cells elastin abundant ground substance Connective Tissue in Embryos Loose Connective Tissue Mesenchyme 400X
nucleus of mesenchymal cell vertebrate embryo * Loose Connective Tissue Mesenchyme 1000X
cells have irregular shapes abundant ground substance vertebrate embryo Adipose and Reticular Tissues Loose Connective Tissue Adipose 100X
adipocytes * Loose Connective Tissue Adipose 400X
nucleus cell membrane Multilocular Adipose Tissue Reticular Connective Tissue 400X
reticular fibers spleen * Reticular Connective Tissue 1000X
reticular fibers spleen Reticular Tissue (Collagen type III) Dense Connective Tissues fibroblast cell nuclei
Dense Regular Connective Tissue 400X fibroblast cell nuclei tendon with densely packed parallel collagen fibers Dense Connective Tissues Dense Irregular Connective Tissue 400X
non-parallel collagen fibers dermis of skin (see slide 12) Dense Connective Tissues Membranes Membranes are simple organs
Form a barrier Composed of epithelium and connective tissue Four types Cutaneous Synovial Serous Mucous Membranes Mucous membranes Line cavities that communicate with the exterior
Contain lamina propria Serous membranes Line sealed internal cavities Form transudate Cutaneous membrane Covers the body surface Synovial membrane Incomplete lining within joint cavities Tissue Injuries and Repairs
2 steps Inflammation Repair Regeneration Fibrosis