The Connective Tissue M. Soleimani , Ph.D.
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Transcript of The Connective Tissue M. Soleimani , Ph.D.
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