Lect. 5 connective tissue components
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  • 1. CONNECTIVE TISSUES:CONNECTIVE TISSUES: COMPONENTSCOMPONENTS Lecture 5: ZOOL 104 (1Lecture 5: ZOOL 104 (1stst Sem. 2013-2014)Sem. 2013-2014) Ms. O. HaraMs. O. Hara
  • 2. CONNECTIVE TISSUES: FunctionsCONNECTIVE TISSUES: Functions  Structural functionStructural function: provide and maintain: provide and maintain FORMFORM inin the body.the body.  Mechanical functionMechanical function: provide a matrix that: provide a matrix that CONNECTSCONNECTS andand BINDSBINDS the cells and organs andthe cells and organs and ultimately gives support to the body.ultimately gives support to the body.
  • 3.  Metabolic functionMetabolic function: Provide metabolic support for: Provide metabolic support for other tissues and organs of the body.other tissues and organs of the body.  Mediate theMediate the EXCHANGEEXCHANGE of nutrients,of nutrients, metabolites and waste products between tissuesmetabolites and waste products between tissues and circulatory system.and circulatory system.  Defense functionDefense function:: serves as the arena and providesserves as the arena and provides the cells that are needed to defend the bodythe cells that are needed to defend the body against invading organisms and other harmfulagainst invading organisms and other harmful substances.substances.
  • 4. CONNECTIVE TISSUES: ComponentsCONNECTIVE TISSUES: Components Structural components:Structural components:  CELLSCELLS – character cells / special support cells– character cells / special support cells  Extracellular matrixExtracellular matrix  ProteinProtein FIBERSFIBERS – (collagen, elastic, reticular)– (collagen, elastic, reticular)  GROUND SUBSTANCEGROUND SUBSTANCE – gel-like arrangement of organic– gel-like arrangement of organic materials where cells and fibers are embedded.materials where cells and fibers are embedded.  imparts strength and rigidity to the matriximparts strength and rigidity to the matrix  BLOOD VESSELSBLOOD VESSELS andand NERVE FIBERSNERVE FIBERS abound.abound.  Structural components:Structural components: Vary inVary in AMOUNTAMOUNT andand COMPOSITIONCOMPOSITION which determine the physicalwhich determine the physical properties of each CT type.properties of each CT type.
  • 5. CONNECTIVE TISSUES: OriginCONNECTIVE TISSUES: Origin  MESODERMMESODERM:: mesodermal cells migratemesodermal cells migrate from their site of origin and surround /from their site of origin and surround / penetrate developing organs.penetrate developing organs.  MESENCHYMEMESENCHYME:: a derivative of mesoderma derivative of mesoderm  embryonicembryonic PRECURSORPRECURSOR of all connectiveof all connective tissues.tissues.  Fibroblasts , chondroblasts, osteoblastsFibroblasts , chondroblasts, osteoblasts  All blood cells and blood vesselsAll blood cells and blood vessels  Cartilage, bones, ligaments, tendons, fasciae,Cartilage, bones, ligaments, tendons, fasciae, musclesmuscles
  • 6. Mesenchymal derivatives:Mesenchymal derivatives: Undifferentiated mesenchymalUndifferentiated mesenchymal cellscells • fibroblastfibroblast • adipocytesadipocytes • chondroblast – chondrocyteschondroblast – chondrocytes • osteoblasts – osteocytesosteoblasts – osteocytes • mesothelial cellsmesothelial cells • endothelial cellsendothelial cells Hematopoietic stem cellsHematopoietic stem cells • Blood cellsBlood cells • RBC,granular WBCRBC,granular WBC • lymphocytes – B cells / T cellslymphocytes – B cells / T cells • Monocytes - macrophagesMonocytes - macrophages • Megakaryocytes – plateletsMegakaryocytes – platelets • OsteoclastOsteoclast • Mast cellsMast cells
  • 7. CELLS of Connective TissuesCELLS of Connective Tissues  Fibroblasts / fibrocytes / reticular cells / adipocytes – derived from undifferentiated mesenchymal cells. - FIXED CELLS in CTs / remain in CTs  Mast cells, macrophages, and plasma cells - originate from hematopoietic stem cells in the bone marrow - circulate in the blood - WANDERING CELLS move to CTs, where they remain and execute their functions. 
  • 8.  Blood leukocytes - are TRANSIENT CELLS of CTs also - originate in bone marrow - they usually migrate to CTs where they reside for a few days and die.
  • 9. Functions of Connective Tissue CellsFunctions of Connective Tissue Cells Cell type Representative product or activity Function Fibroblast, chondroblast, osteoblast Production of fibers and ground substance Structural Plasma cell Production of antibodies Immunological (defense) Lymphocyte (several types) Production of immunocompetent cells Immunological (defense) Eosinophilic leukocyte Participation in allergic and vasoactive reactions, modulation of mast cell activities and the inflammatory process Immunological (defense) Neutrophilic leukocyte Phagocytosis of foreign substances, bacteria Defense Macrophage Secretion of cytokines and other molecules, phagocytosis of foreign substances and bacteria, antigen processing and presentation to other cells Defense Mast cell and basophilic leukocyte Liberation of pharmacologically active molecules (eg, histamine) Defense (participate in allergic reactions) Adipose (fat) cell Storage of neutral fats Energy reservoir, heat production
  • 10. FIBROBLAST: Active and quiescent stagesFIBROBLAST: Active and quiescent stages FIBROBLASTFIBROBLAST - the dominant cells in the CT- the dominant cells in the CT FIBROCYTESFIBROCYTES  Has an abundant and irregularly branchedHas an abundant and irregularly branched cytoplasmcytoplasm  Nucleus is ovoid, large, and pale staining, withNucleus is ovoid, large, and pale staining, with fine chromatin and a prominent nucleolus.fine chromatin and a prominent nucleolus.  Cytoplasm is rich in rERCytoplasm is rich in rER  Golgi complex is well developedGolgi complex is well developed  SynthesizeSynthesize collagen, reticular, andcollagen, reticular, and elastic fiberselastic fibers  SynthesizeSynthesize constituents of theconstituents of the extracellular matrix.extracellular matrix.  The spindle-shaped fibrocytes are smallerThe spindle-shaped fibrocytes are smaller than the fibroblasts and are maturethan the fibroblasts and are mature  Less active cells of the fibroblast line.Less active cells of the fibroblast line.  It has fewer processesIt has fewer processes  Has a smaller, darker, elongated nucleus;Has a smaller, darker, elongated nucleus;  With acidophilic cytoplasmWith acidophilic cytoplasm  Has a small amount of rERHas a small amount of rER
  • 11. FIBROBLASTFIBROBLAST FIBROCYTESFIBROCYTES
  • 12. MACROPHAGES or HISTIOCYTES  Derived from circulating blood MONOCYTES that take up residence in the connective tissue.  PHAGOCYTIC cells that ingest bacteria, dead cells, cell debris, and other foreign matter in the CT  Enhance immunologic activities of the lymphocytes.  ANTIGEN-PRESENTING CELLS (APC) to lymphocytes and perform an important function in the immune response  Macrophages have specific names in different organs
  • 13. Macrophage:Macrophage: •usually appears round with irregular cell outlines, butusually appears round with irregular cell outlines, but exhibits aexhibits a VARIABLE APPEARANCEVARIABLE APPEARANCE • small nucleus rich in chromatin and cytoplasm filled withsmall nucleus rich in chromatin and cytoplasm filled with dense,dense, INGESTEDINGESTED particles.particles. •When a vital dye such as trypan blue or India ink isWhen a vital dye such as trypan blue or India ink is injected into an animal, macrophages engulf andinjected into an animal, macrophages engulf and accumulate the dye in their cytoplasm in the form ofaccumulate the dye in their cytoplasm in the form of granules or vacuoles visible in the light microscopegranules or vacuoles visible in the light microscope
  • 14. Distribution and Main Functions of the Cells of the Mononuclear Phagocyte System. Cell Type Location Main Function Monocyte Blood Precursor of macrophages Macrophage Connective tissue, lymphoid organs, lungs, bone marrow Production of cytokines, chemotactic factors, and several other molecules that participate in inflammation (defense), antigen processing and presentation Kupffer cell Liver Same as macrophages Microglia cell Nerve tissue of the central nervous system Same as macrophages Langerhans cell Skin Antigen processing and presentation Dendritic cell Lymph nodes Antigen processing and presentation Osteoclast Bone (fusion of several macrophages) Digestion of bone Multinuclear giant cell Connective tissue (fusion of several macrophages) Segregation and digestion of foreign bodies
  • 15. MAST CELLSMAST CELLS  oval to round CT cellsoval to round CT cells  10–13µm in diameter10–13µm in diameter  cytoplasm is filled withcytoplasm is filled with BASOPHILICBASOPHILIC secretorysecretory granulesgranules  With centrally located small, spherical nucleusWith centrally located small, spherical nucleus which is frequently obscured by the cytoplasmicwhich is frequently obscured by the cytoplasmic granules.granules.  synthesize and releasesynthesize and release HISTAMINEHISTAMINE andand HEPARINHEPARIN..  Exposure of mast cells toExposure of mast cells to ALLERGENSALLERGENS causescauses rapid release of histamine and other vasoactiverapid release of histamine and other vasoactive chemicals.chemicals.
  • 16. Mast cells LM EM G - Granules containing histamine and heparin M – mitochondria N – nucleus E – elastic ; C- collagen fibrils
  • 17. 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.
  • 18. ADIPOSE CELLS / ADIPOCYTESADIPOSE CELLS / ADIPOCYTES  Fixed cells in loose CTFixed cells in loose CT  Adipocytes are very long-lived cells. Their number isAdipocytes are very long-lived cells. Their number is determined by the number ofdetermined by the number of LIPOBLASTLIPOBLAST (pre-(pre- adipocyte) ) generated during fetal and earlyadipocyte) ) generated during fetal and early postnatal development.postnatal development.  Function:Function: STORE FATSTORE FAT (lipid), provide(lipid), provide PROTECTIVEPROTECTIVE packing material in and around numerous organs andpacking material in and around numerous organs and for the production offor the production of HEATHEAT..
  • 19. Adipocytes • exhibits a narrow rim of cytoplasmexhibits a narrow rim of cytoplasm • flattened, eccentric nucleusflattened, eccentric nucleus • In histologic sections, the largeIn histologic sections, the large fat globulesfat globules of adipose cellsof adipose cells have been dissolved by different chemicals, leaving a large,have been dissolved by different chemicals, leaving a large, highly characteristichighly characteristic EMPTYEMPTY space.space.
  • 20. PLASMA CELLSPLASMA CELLS  Derived fromDerived from B LYMPHOCYTESB LYMPHOCYTES that have beenthat have been exposed to antigens.exposed to antigens.  Plasma cells producePlasma cells produce ANTIBODIESANTIBODIES of importanceof importance in immune reactions.in immune reactions.  Large, ovoid cells that have aLarge, ovoid cells that have a BASOPHILICBASOPHILIC cytoplasm due to their richness in roughcytoplasm due to their richness in rough endoplasmic reticulumendoplasmic reticulum  Exhibits a smaller, eccentrically placed nucleus withExhibits a smaller, eccentrically placed nucleus with condensed, coarse chromatin clumps distributedcondensed, coarse chromatin clumps distributed peripherally in a characteristic radial (cartwheel)peripherally in a characteristic radial (cartwheel) pattern and one central mass.pattern and one central mass.
  • 21. Plasma cells •A prominent,A prominent, CLEAR AREACLEAR AREA ((golgi complexgolgi complex) in the) in the cytoplasm is adjacent to the nucleus.cytoplasm is adjacent to the nucleus. • Golgi complex - is where theGolgi complex - is where the terminal glycosylationterminal glycosylation of the antibodies (glycoproteins) occurs.of the antibodies (glycoproteins) occurs.
  • 22. LEUKOCYTES  White blood corpuscles / white blood cells (WBC)White blood corpuscles / white blood cells (WBC)  WANDERINGWANDERING cells of the connective tissue.cells of the connective tissue.  Basophils, neutrophils, eosinophils, lymphocytes, monocytesBasophils, neutrophils, eosinophils, lymphocytes, monocytes  macrophagemacrophage  The normal CT contains leukocytes that migrate through theThe normal CT contains leukocytes that migrate through the walls of blood vessels from the blood to CT by a processwalls of blood vessels from the blood to CT by a process calledcalled DIAPEDESISDIAPEDESIS..  Neutrophils and MonocytesNeutrophils and Monocytes  secretesecrete ENZYMEENZYME that degrade the basement membranethat degrade the basement membrane between the endothelial cells – to squeeze into the site ofbetween the endothelial cells – to squeeze into the site of infectioninfection  DIAPEDESISDIAPEDESIS  WBCs must aggregate in the CT area to mediateWBCs must aggregate in the CT area to mediate INFLAMMATORYINFLAMMATORY process.process.
  • 23. Fig. 1. Leukocyte extravasation is controled by a cascade of adhesion andFig. 1. Leukocyte extravasation is controled by a cascade of adhesion and signalling molecules. First leukocytes are captured to the blood vessel wall bysignalling molecules. First leukocytes are captured to the blood vessel wall by selectinsselectins. Sensing chemotactic factors such as. Sensing chemotactic factors such as chemokineschemokines on theon the endothelial cell surface leads to the activation of leukocytes and leukocyteendothelial cell surface leads to the activation of leukocytes and leukocyte integrinsintegrins. Finally leukocytes migrate along the blood vessel wall and through. Finally leukocytes migrate along the blood vessel wall and through the endothelial cell layer and the underlying basal lamina.the endothelial cell layer and the underlying basal lamina. Source: http://celldynamics.uni-muenster.de/Projects/ProB1txt.htmlSource: http://celldynamics.uni-muenster.de/Projects/ProB1txt.html DiapedesisDiapedesis
  • 24. Increased vascular permeability  caused by the action of vasoactive substances  Ex. Histamine - from mast cells and basophils  vascular permeability  Increases in blood flow  responsible for local swelling (edema), redness, and heat.  Pain is due to chemical mediators on nerve endings. Chemotaxis – when specific cell types are attracted by some molecules, is responsible for the migration of large quantities of specific cell types to regions of inflammation.  leukocytes cross the walls of venules and capillaries by diapedesis, invading the inflamed areas.
  • 25. Leukocytes • NeutrophilsNeutrophils - active and powerful- active and powerful PHAGOCYTESPHAGOCYTES;; they engulf and destroy bacteria at sites of infections.they engulf and destroy bacteria at sites of infections. • EosinophilsEosinophils - become active and increase in- become active and increase in number afternumber after PARASITICPARASITIC infections orinfections or ALLERGICALLERGIC Section of an inflamed intestinal lamina propria. Inflammation was caused by nematode parasitism. Aggregated eosinophils and plasma cells function mainly in the CT by modulating the inflammatory process. Giemsa stain. LPO
  • 26. CT Component: EXTRACELLULAR MATRIX - GROUND SUBSTANCE  fills the space between cells & fibers of the CTfills the space between cells & fibers of the CT  a highlya highly HYDRATEDHYDRATED, colorless, and transparent, colorless, and transparent complex mixture of macromolecules.complex mixture of macromolecules. (Water, salts and other low molecular substances & proteoglycans) VISCOUSVISCOUS..  Acts as both a lubricant and aActs as both a lubricant and a barrierbarrier to theto the penetration of invaderspenetration of invaders
  • 27. GROUND SUBSTANCE : CompositionComposition  GLYCOSAMINOGLYCANSGLYCOSAMINOGLYCANS (GAGs) (formerly “acid(GAGs) (formerly “acid mucopolysaccharides)mucopolysaccharides).  PROTEOGLYCANSPROTEOGLYCANS (formerly “mucoproteins”)(formerly “mucoproteins”)  MultiadhesiveMultiadhesive GLYCOPROTEINSGLYCOPROTEINS..
  • 28. Glycosaminoglycans, GAGsGlycosaminoglycans, GAGs (Acid mucopolysaccharides)(Acid mucopolysaccharides)  LINEAR POLYSACCHARIDES formed by repeating disaccharide units that are bound covalently to proteoglycan molecule.  intensely hydrophilic and act as polyanions  Heparan sulfateHeparan sulfate  Keratan sulfateKeratan sulfate  Dermatan sulfateDermatan sulfate  Chondroitin sulfateChondroitin sulfate  Hyaluronic acidHyaluronic acid
  • 29.  The core protein associated with the four main GAGs  CARBOHYDRATE moiety predominates (80-90%)  bind to a great number of cations (usually sodium) by electrostatic (ionic) bonds  intensely hydrated structures with a thick layer of SOLVATION water surrounding the molecule – VISCOUS  act as a barrier to the penetration of bacteria and other microorganisms Purposes:  Act as STRUCTURAL components of the extracellular matrix  ANCHORING cells to the matrix  Bind many protein growth factors (eg, transforming growth factor, TGF-, of fibroblasts). GAG + Protein core = PROTEOGLYCANS
  • 30. Proteoglycan  EXTRACELLULAR proteoglycans  In the matrix  Ex. Aggrecan (in cartilage)  SURFACE proteoglycans  attached to the surface of many types of cells, particularly epithelial cells.  Ex. syndecan and fibroglycan
  • 31. GLYCOPROTEIN  Globular PROTEIN molecules to which branched chains of MONOSACCHARIDES are covalently attached.  Protein moiety usually predominates  play an important role in the INTERACTION between neighboring adult and embryonic cells  For the adhesion of cells to their substrate Ex. Fibronectin - has binding sites for cells, collagen, and GAGs. - help to mediate normal cell adhesion and migration
  • 32. TISSUE FLUID  Very small quantity of fluid in the extracellular matrix (ECM) of CTs that comes from the BLOOD  Due to HYDROSTATIC pressure of the blood, small amount of plasma fluid passes through the capillary walls.  Since CTs are widely distributed, as much as one-third of the plasma proteins of the body are STORED in the ECM of the connective tissue.  EDEMA – in pathological conditions, it is promoted by the accumulation of water in the extracellular spaces due to increased VASCULAR permeability.
  • 33. Movement of fluid through connective tissue. There is a decrease in hydrostatic pressure and an increase in osmotic pressure from the arterial to the venous ends of blood capillaries (upper part of drawing). Fluid leaves the capillary through its arterial end and repenetrates the blood at the venous end. Some fluid is drained by the lymphatic capillaries.
  • 34. A. CT fibersA. CT fibers 1) Collagen fibers1) Collagen fibers  Dominant fiber type in most CT.Dominant fiber type in most CT.  OrgansOrgans: Throughout the body: Throughout the body FxnFxn: Add strength to the CT.: Add strength to the CT.  Component:Component: Microfibrils (collagen fibrils) which areMicrofibrils (collagen fibrils) which are assemblies of tropocollagen (ofassemblies of tropocollagen (of AAs: hydroxyprolineAAs: hydroxyproline and hydroxylysine).and hydroxylysine).  TypesTypes I, II and III tropocollagens are the major fiberI, II and III tropocollagens are the major fiber formers.formers.  Tropocollagen IV is an important structuralTropocollagen IV is an important structural component of thecomponent of the BASAL LAMINABASAL LAMINA..
  • 35. Medical significance:  KELOIDKELOID – abnormal amount of collagen fibers– abnormal amount of collagen fibers formed in the scars of the skin.formed in the scars of the skin.  SystemicSystemic SCLEROSISSCLEROSIS – excessive accumulation of– excessive accumulation of collagen in skin, digestive tract, kidneys – hardenedcollagen in skin, digestive tract, kidneys – hardened and dysfunctional impairment of organs affectedand dysfunctional impairment of organs affected (fibrosis).(fibrosis).
  • 36.  Vitamin C deficiency (Vitamin C deficiency (SCURVYSCURVY) – hydroxylation of) – hydroxylation of prolyl and lysyl residues (AAs) in the endoplasmicprolyl and lysyl residues (AAs) in the endoplasmic reticulum can be inhibited, producing defectivereticulum can be inhibited, producing defective collagen (non-reversible) –collagen (non-reversible) – DEGENERATIONDEGENERATION ofof connective tissue.connective tissue.  Vit. C is aVit. C is a COFACTORCOFACTOR of proline hydroxylase.of proline hydroxylase.
  • 37. 2) Reticular fibers  Very delicate and form fine networks instead of thickVery delicate and form fine networks instead of thick bundles.bundles.  Affinity with special stains.Affinity with special stains. Ex:Ex: SILVERSILVER stainedstained sections reticular fibers look like fine,sections reticular fibers look like fine, blackblack threads.threads. Their different staining characteristics were initiallyTheir different staining characteristics were initially thought that reticular fibers were completelythought that reticular fibers were completely different from collagen fibres.different from collagen fibres.  Component:Component: TypeType IIIIII collagencollagen  Fxn:Fxn: Support to individual cells of Muscle & AdiposeSupport to individual cells of Muscle & Adipose tissues andtissues and CAPSULATEDCAPSULATED organs (liver & spleen);organs (liver & spleen); tunica media of muscular arterytunica media of muscular artery
  • 38. Liver, reticular fibers
  • 39. 3) Elastic fibers • In fresh tissuesIn fresh tissues: Light yellow in large amounts in the: Light yellow in large amounts in the tissue.tissue. • Special stains:Special stains: Resorcin fuchsinResorcin fuchsin gives a dark violetgives a dark violet color.color. • ComponentComponent:: The matrix accounts for about 90% ofThe matrix accounts for about 90% of the fiber and composed ofthe fiber and composed of elastinelastin and microfibrils.and microfibrils. Both elastic fibers and microfibrils are not collagen..Both elastic fibers and microfibrils are not collagen.. • Organs:Organs: Elastic ligaments of the vertebral column;Elastic ligaments of the vertebral column; ear auricles; skin dermis; aorta; large arteriesear auricles; skin dermis; aorta; large arteries
  • 40. •Can be stretched to about 150% of their original length. Elastin fibersCan be stretched to about 150% of their original length. Elastin fibers remains unfolded as a "random coil".remains unfolded as a "random coil". • They resume their original length if the tensile forces applied to theThey resume their original length if the tensile forces applied to the elastic fibers are relaxed.elastic fibers are relaxed. • Fibers are cross-Fibers are cross- linked to eachlinked to each other byother by desmosindesmosin andand isodesmosinisodesmosin found betweenfound between elastin molecules.elastin molecules.
  • 41. Elastic fibers, Aorta
  • 42. References:  Junquiera LC, Carneiro J. 2005. BASIC HISTOLOGY : TEXT AND ATLAS 11th Edition. McGraw-Hill’s ACCESS MEDICINE.  Young B. 2009. WHEATER’S FUNCTIONAL HISTOLOGY. 5TH Edition. UK: Churchill Livingstone. Distributor: Phils: C & E Publishing, Inc.