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EMBRYONIC CONNECTIVE TISSUE CONNECTIVE TISSUE PROPER
ADIPOSE TISSUE
q Adult connective tissuesØConnective tissue proper§ Loose (alveolar) § Reticular§ Dense irregular§ Dense regularü Collagenousü Elastic§ Adipose
q Embryonic connective tissues ØMesenchymal ØMucous
q Specialized connective tissues ØSupporting tissues § Cartilage § Bone § Blood
Categories of connective tissues
CONNECTIVE TISSUES Ø They have the same origin – mesenchyme and the same structure
(cells and extracellular matrix), Ø Unlike epithelial cells, connective tissue cells are widely seperated
by components of extracellular matrix.
Cells of connective tissue + extracellular matrix (ECM)
Epithelial tissue
Closely aggregated polyhedral cells and very little extracellular matrix Epithelia are derived from all germinal layers
Connectivetissue
Connective tissue is composed of two elements: ØCells ØExtracelullar matrix [ECM] ü Fibers −collagen fibers, elastic fibers, reticular fibers ü Ground substance
Extracellular matrix = Fibers + ground substance
Cells of connective tissues (CTs)v Connective tissue proper − fibroblasts, fibrocytes v Adipose tissue – adipoblasts, adipocytes v Cartilage – chondroblasts, chondrocytes v Bone – osteoblasts, osteocytes v Blood – formed elements (erytrocytes, leukocytes)
Cells of Connective Tissue (CT) proper
ØThe cells spend all their live in the tissue
§ Fibroblasts – originate from undifferentiated mesenchymal cells, produce ECM components, can proliferate
§ Fibrocytes – quiescent fibroblasts
Two stages of activity
The active cells The quiescent cells
↓ ↓Fibroblasts Fibrocytes
Fibroblasts _ Fibrocytes ü Fibroblasts § the most common cells
in connective tissue § branched cytoplasm § ovoid, large and pale
staining nucleus with nucleolus § rich in RER and well developed Golgi complex § responsible for the
synthesis of ECM components§produce the growth
factors § proliferate when the
additional fibroblasts are required
ü Fibrocytes § smaller than
fibroblasts§ fewer processes § smaller, darker,
elongated nucleus § small amount of
RER
The function of connective tissues
Ø Providing structural support Ø Serving as a medium for exchange Ø Aiding in the defense and protection of the body Ø Forming a site for storage of fat
The function of connective tissue proper
Ø Forms the capsules of organs and membranes that enveloped the central nervous system (meninges)
Ø Forms trabeculae and walls inside several organs – components of the stroma within organs
Ø Medium for exchange of metabolic waste, nutrients and oxygen between the blood and many of cells in the body
The cells which reside in the tissue
§ Macrophages§ Mast cells§ Plasma cells§ Leukocytes
Macrophages → the Mononuclear Phagocyte System ØMorphological features reflect functional activity of macrophages: § they have pseudopodia, only in macrophages § irregular surface with and protrusions – pinocytotic and
phagocytic activities§ oval or kidney-shaped nucleus located centrally § well-developed Golgi complex, many lysosomes, prominent
rough endoplasmic reticulum (RER)
ü Macrophages derive from monocytes of blood
ØMacrophages are long-living cells, can proliferate locally. The cells are distributed throughout the body, and in certain region have special names: § histocytes – the connective tissue proper § Kupffer cells – the liver § microglia cells – the central nervous system § osteoclasts – the bone
φ 10 – 30 µm
Macrophages functionsØ phagocytosis of foreign substances and bacteria Ø antigen processing and presentation to other cells
(Antigen Presenting Cells – APC) Ø secretion of cytokines and other molecules § enzymes, eg. collagenase Ø removing cell debris and damaged extracellular components
Ø Macrophages when stimulated § may increase in size and are arrangement in clusters forming epithelioid
cells;§ may fuse to form multinuclear giant cellsØ Epithelioid cells and giant cells are found only in pathological conditions.
Multinuclear giant cells
Mast cells
Ø Oval to round connective tissue cells Ø The cytoplasm is filled with basophilic secretory granules Ø Small, spherical nucleus, situated centrally
v Secretory granules of mast cells § they contain biological active substances: ü histamine - promotes an increase in vascular permeabilityü heparin - (sulfated glycosaminoglycan is blood anticoagulant)ü neutral proteases ü chemotactic factor for eosinophils
§ substances not stored in the granules: ü leukotriens (C4, D4, E4)
φ 10 – 13 µm
derive from cells of the bone marrow
q The connective tissue mast cells§ skin and peritoneal cavity
q The mucosal mast cells§ the connective tissue of the intestinal
mucosa and lungs
Mast cells
vThe surface of mast cells contains specific receptors for immunoglobulin E(IgE), a type of immunoglobulin produced by plasma cells
Leukocytes
Diapedesis
or white blood cells Øthe wandering cells of connective
tissue Øthey migrate through the walls of
capillaries and postcapillary venules from the blood to connective tissue (diapedesis)
v Granulocytes
v B and T Lymphocytes
ØPlasma cells
Ø B lymphocyte → plasma cell → synthesis of immunoglobulins
Ø large, ovoid cells with basophilic cytoplasm, very well developed RER, The Golgi complex
Ø spherical nucleus, placed eccentrically Ø average of live is short, 10 – 20 days.
Adipose cells
Ø Adipose cells, adipocytes, fat cells § the connective tissue cells for
storage of neutral fats or for the production of heat
The extracellular matrix
ØFibers § Collagen fibers § Elastic fibers § Reticular fibers
ØGround substance § Glycosaminoglycans (GAGs)§ Proteoglicans § Multiadhesive glycoproteins
Fibers
v Collagen fibers ü are formed by protein collagen ü the collagen is the most abundance protein in the human body (30% of dry weight) ü the collagens belong to a family of more than 25 members, produced by several
cells type üare acidophilic; stain pink with eosin, blue with Mallory’s stain
eosin Mallory’s
ØThe cell type responsible for collagen synthesis§ fibroblasts, chondrocytes, osteoblasts § odontoblasts § endothelial cells § vascular smooth muscle cells
ØThe collagen profile • the principal amino acids – glycine (33.5%), proline (12%), hydroxyproline (10%) • amino acids that are characteristic of the collagen – hydroxyproline and hydroxylysine
Collagen types
v Type I − the abundant: skin, tendon, bone, dentinv Type II − cartilage, vitreous bodyv Type III − skin, muscle, blood vesselsv Type IV − all basement membranes v Type V − fetal tissue, skin, bone, placentav Type VII – epithelia – anchors skin epidermal basal lamina to underlying stroma
(anchoring fibrils)
Collagen is a protein polymer composed of monomeric units of the proteinTropocollagen
Tropocollagen Three α chains
§ elongated protein 280 nm in length and 1.5 nm in width
Structural arrangement of collagen: 1) Collagen is arranged into microfibrils.2) Microfibrils are arranged into fibrils.3) Fibrils are grouped into a fiber.4) Fibers are grouped into a collagen bundle
Collagen synthesis
v Hydroxylation of proline and lysine§ peptidyl proline hydroxylase § peptidyl lysine hydroxylase Co-factors: O2, Fe, vit. C
v Glycosylation of hydroxylysine § transferases Mn
v Removing of registration peptides § procollagen peptidases § tropocollagen
v Formation of covalent cross-links between tropocollagen molecules § lysyl oxidase Cu and O2 ions
v Procollagen synthesis § Registration peptides on both
amino-terminal and carboxy-terminal ends
§ precursor of tropocollagen
Vitamin C (ascorbic acid) deficiency leads to the scurvy, disease characterizedby the degeneration of connective tissue. Scurvy characterized by bleddinggums and loose teeth among other symptomsVitamin C deficiency → abnormal hydroxylation of procollagen → synthesis ofdefective collagen
Reticular fibers
Øconsist mainly of type III collagen Øextremely thinØstain black by impregnation with silver salts – agyrophylic fibers
ØLocalization § are particularly abundant in smooth muscle tissue§ endoneurium § spleen, lymph nodes, bone marrow § constitute a network around the cells of parenchymal organ, eg. liver,
endocrine glands § the wall of arteries
Reticular fibers
Elastic fibers Ø Elastin – the main component + microfibrillsØ Proelastin - precursor of elastin Ø Elastin is rich in glycin and proline Ø Contains two unusual amino acids – desmosine and
isodesmosine formed between four lysinesØ has rubberlike qualities Ø stains brown with orcein and violet with
resorcine-fuchsin
v Elastoblasts § Fibroblasts § Chondrocytes § Vascular SMC § Endothelial cells
They are composed of an amorphous elastin surrounded by a microfibrillar component consisting of fibrillin
The elastic fibers system
ØOxytalan fibers§ zonule fibers of the eye § dermis q do not contain elastin q consist of a bundle of 10nm
microfibrils composed of glycoproteins: fibromodulin I and II, and fibrillin.
ØElaunin fibers§ around sweet glands § dermis q irregular deposits of
elastin between the microfibrils
ØElastic fibers§ the wall of large arteries § connective tissues q elastin located
centrally and thin sheath of microfibrils
q the most numerous component of the system
Microfibrils
Elastin
Ground substance
Øhighly hydrated, colorless and transparent complex mixture of macromolecules Øit fills the space between cells and fibers Øit is viscous and acts as lubricant and barrier to the penetration of invaders
v Glycosaminoglycans (GAGs)v Proteoglycans v Multiadhesive glycoproteins
Glycosaminoglycans (GAGs)
Øcalled mucopolysaccharides
- dermatan sulfate - chondroitin sulfate - keratan sulfate - heparan sulfate- hyaluronic acid
Øwith the exception of hyaluronic acid GAGs are bound covalently to a protein core, forming proteoglycans
Øwith the exception of hyaluronic acid all other GAGs are sulfated ØGAGs are intensely hydrophilic and act as polyanions
Proteoglycans Ø are composed of a core protein associated with the four main GAGs (without
hyaluronic acid) Ø proteoglycan (monomer) is three-dimensional structure (can be pictured as test
tube brush)
Proteoglycan monomer
Core protein
q Proteoglycans of extracellular matrix (ECM) § aggrecan – the most important, the
dominant in cartilage § syndecan, fibroglycan
v Proteoglycans are degradated by several cell types (lysosomal enzymes). Lysosomal enzymes deficiency causes several disorders in humans(eg. Mucopolysaccharidoses )
Proteoglycan aggregates
Schematic representation of the proteoglycan aggrecan
Functions: ü structural component of ECM ü anchoring cells to the ECM ü as extracellular and surface
proteoglycans bind many protein growth factors (TGF-β→ transforming growth factor)
Multiadhesive glycoproteins
Ø play an important role in the interaction between neighboring adult and embryonic cells
Ø play role in the adhesion of cells to their substrate
Protein
v Fibronectin § the product of fibroblasts and epithelial cells § has sites to bind cells, collagen and GAGs
v Laminin § participates in the adhesion of epithelial cells to basal lamina
v Matrix receptors are cell-surface molecules. Cells bind to collagen, fibronectin, laminin
§ Integrins – transmembrane linker proteins, interact with the cytoskeleton
v Intracellular proteins – the interaction between integrins, ECM, cytoskeleton elements
§ Paxilin§ Vinculin§ Talin
Embryonic connective tissues Mesenchyme
Ø The precursor embryonic tissue for all types of connective tissue Ø Stellate undifferentiated cells and ground substance Ø The lack of fibers Ø Under specific stimuli the cells differentiate into the cells of connective tissue -
fibroblasts, adipoblasts, chondroblasts, osteoblasts, blood cells
Ø Mucous connective tissue § has a abundance of ground substance rich in hyaluronic acid § is jellylike tissue containing very few collagen fibers type I and type III § the cells – mainly fibroblasts§ is found in umbilical cord and is referred to as Wharton’s jelly § is found in the pulp of young teeth
Umbilical cord
Embryonic connective tissues Mucous
Adult connective tissues The connective tissue proper
Loose connective tissue
ØLoose connective tissue § the very common type of connective tissue § fills spaces between groups of muscle cells, supports epithelial tissue, forms
layer around lymphatic and blood vessels. § is found in dermis, hypodermis, mucous membranes § has delicate consistency, well vascularized, not very resistant to
stress
Ø Reticular connective tissue § consists of reticular fibers (type III collagen) and specialized fibroblasts named
reticular cells § reticular tissue creates the special microenvironment for hematopoietic organs
and lymphoid organs (bone marrow, lymph nodes, spleen), and envelops certain cells (eg. hepatocytes)
Reticular cell
Reticular fibers
Dense connective tissue (CT)Øis adapted to offer resistance and protection Øthere are fewer cells than loose connective tissue and high amount of collagen fibers
ØDense irregular CT§ the collagen fibers are arranged in bundles without a definite orientation § provide resistance to stress from all directions § is found in dermis
Collagen fibers Fibrocytes
ØDense regular CT (collagenous)§ the collagen bundles are arranged in the definite pattern § it is found in tendons
§ the collagen fibers have parallel, closely packed bundles of collagen separated by a small quantity of intracellular ground substance § fibrocytes have elongated nuclei parallel to the fibers § the cytoplasm of fibroblasts stains the same color as the
fibers
Tendon
Collagen fibers
Nuclei of fibrocytes
Ø Dense regular CT (elastic) § is composed of bundles of thick parallel elastic fibers § the spaces between the fibers are occupied by thin collagen fibers and flattened
fibroblasts § is found in yellow ligaments of the vertebral column, suspensory ligament of the penis
Aorta
Elastic laminae beetwen themvascular smooth muscle cells
fibrocytes
Adipose tissue
ØSpecial type of the connective tissue with predomination of adipose cells(adipocytes, fat cells)
ü Adipocytes § as isolated cells, in small aggregates (adipose tissue)
Adipose tissue
v Unilocular adipose tissue (common or yelow)
v Multilocular adipose tissue (brown)
Adipose tissue is found in a variety of places such as:1] the hypodermis2] surrounding and protecting certain organs3] the medullary cavity of long bones
Functions:1] stores energy2] contributes to the thermal
insulation of the body 3] protects delicate organs from
mechanical trauma
Unilocular (common or yelow) adipose tissue
ØThe color varies from white to dark yelow (depends on diet – carotenoids) ØThe distribution is determined by age and sex § in the newborn has uniform thickness in the body § its distribution is partly regulated by sex hormones and adrenocortical hormones
(different distribution in male and female body)
Spherical, isolated cell
Lipid droplet
Nucleus
Cytoplasm
Signet ring cells
Lipids are removedin routine
histological techniques
Polyhedral cells in
adipose tissue Sudan III
Unilocular (common or yelow) adipose tissue
Vimentin intermediate filament
Basal lamina
φ 50 – 150 µmØCytoplasm§ Golgi complex § mitochondria § poorly developed RER§ SER § free polyribosomes § pinocytotic vesicles
v Adipose tissue ü is richly vascularized
Unilocular (common or yelow) adipose tissue
ØLarge depot of energy for organism Ø Metabolism of adipose tissue is regulated by hormones
Adipose tissue as a secretory organ
Ø enzymes – lipoprotein lipase Ø leptin Ø adiponectin Ø adipsin ØTNFα (Tumor Necrosis Factor α) Ø source of estrogen (estrone) in postmenopausal women
Multilocular adipose tissue (brown fat)
ØMultilocular tissue cells are polygonal and smaller thanunilocular adipose cells
ØThe cytoplasm contains § great number of lipid droplets of various sizes § spherical and central nucleus § numerous mitochondria with abundant long cristae
(containing colored cytochromes) ØThe cells receive direct sympathetic innervation ØThe tissue is rich in capillaries
Distribution of multilocular adipose tissue
Ø In humans the tissue is important mainly in the first postnatal life (produces heat and protects the newborn against cold)
ØIt is greatly reduced in adulthoodØThe tissue is more abundant in hibernating animals – hibernating gland
In human newborn the multilocular adipose tissue constitutes 2 - 5% of the body weight
v Mainly around the shoulder blades and kidneys
Function of the multilocular adipose tissue
ØThe main function is to produce heat ØThe production is stimulated when human newborn or animals are exposed to
the cold environment ØMitochondria of multilocular adipocytes contain transmembrane protein –
thermogenin → heat production (temperature of tissue is elevated)
Slides
v Mesenchyme
Embryo head
ØMucous tissue
The umbilical cord - Warthon’s jelly
Arteries
Vein
ØLoose connective tissue ü Nuclei of fibrocytes and others cells ü Collagen fibers ü Elastic fibers
Elastic fibers
Collagen fibers
ØDense connective tissue
v Dense regular CT v Dense irregular CT
Tendon Skin
ØAdipose tissue
Sudan III
Signet ring cells
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