Support cells and the extracellular matrix Flashcards
2 types of cells forming tissues
parenchymal cells
support cells
parenchymal cells
subserve main function of a tissue
support cells
provide structural scaffolding of a tissue
highly developed
complex metabolic functions
produce an extracellular matrix which defines physical characteristics of a tissue
connective tissue
support cells and their extracellular matrix
characteristics of support cells
embryological derivation from mesenchyme
production of various extracellular matrix materials
formation of sparsely cellular tissues when mature
cell adhesion mechanisms interacting with extracellular matrix materials
mesenchyme
embryonic tissue
develops from any of 3 germ layers
spindle shaped cells with large nuclei
develop into family of support cells
5 classes of support cells
fibroblasts chondrocytes osteoblasts myofibroblasts adipocytes
fibroblasts
secrete extracellular matrix components in most tissues, usually collagen and elastin
chondrocytes
secrete extracellular matrix components of cartilage
osteoblasts
secrete extracellular matrix components of bone
myofibroblasts
secrete extracellular matrix components and have a contractile function
adipocytes
specially adapted lipid-storing support cells
act as energy store
cushioning and padding function
extracellular matrix composition
glycosaminoglycans (GAG)
fibrillar proteins
small amounts of structural glycoprotein for cell adhesion
structure of support tissue
scattered network of support cells
organised, abundant extracellular network of fibrillar proteins arranged in a hydrated gel of GAG
glycosaminoglycans
large polysaccharides
give turgor
determine diffusion of substances
polysaccharides link to backbone proteins to form proteoglycans
proteoglycans
polysaccharides linked to backbone proteins
4 groups of GAG
hyaluronic acid
chondroitin sulfate and dermatan sulfate
heparin sulfate and heparin
keratan sulfate
hydrated gel matrix
formed by 4 groups of GAG
properties determined by charge and spatial arrangement
properties of GAG
high negative charge
strong hydrophilic behaviour
retention of positive ions and water
covalent attachment to proteins to form proteoglycans (except hyaluronic acid)
high negative charge
one of the repeating units in GAG is an amino sugar (N-acetylglucosamine or N-acetylgalactosamine), commonly sulfated (SO3-) and commonly the second sugar is uronic acid with a carboxyl group (COO-)
strongly hydrophilic behaviour
cannot fold into compact structures
large, permanently open coil conformation
retention of positive ions and water
maintaining tissue architecture due to inherent turgor, preventing deformation by compressive forces
covalent attachment to proteins to form proteoglycans
except hyaluronic acid
maintain large hydration space
allow variation in pore size of gel
basement membranes of kidney glomerulus
hyaluronic acid properties
not sulfated or protein linked
other GAG properties
sulfated and protein linked
4 proteins forming fibrils in extracellular matrix
collagen
fibrillin
elastin
fibronectin
role of fibrillar proteins
provide different tensile properties to support tissues
anchorage for other cellular elements in tissues
collagens
family of closely related proteins
aggregate to produce filaments, fibrils or mesh works- interact with other proteins to provide support
types of collagen chains
20 types of collagen polypeptide chains (alpha chains) produced from different genes
combine to form different morphologic forms
collagen families
fibrillar collagens facit collagens short-chain collagens basement membrane collagens other collagens
fibrillar collagens
types I, II, III, V, XI
facit collagens
fibril associated collagen with interrupted triple helix
types IX, XII, XIV
short chain collagens
types VIII, X
basement membrane collagens
type IV
other collagens
VI, VII, XIII
collagen types I, II, III
arranged as rope-like fibrils - main forms of fibrillar collagen
type I
large banded collagen fiber
resist tensile stresses
pink staining materials
skin dermis, tendon, bone, ligaments, fascia, fibrous cartilage, cornea, loose fibrous tissue
type II
small banded collagen fibre
hyaline and elastic cartilage, vertebral disks, vitreous of eye
type III
small banded collagen fibre
blood vessels, parenchymal organs, bone marrow, lymphoid tissue, smooth muscle, nerves, lung, fetal skin
reticular fibres
thin fibrils of type III collagen
20nm diameter
loose mesh in support tissues
zone beneath basement membranes - fibroreticular lamina
reticular fibres in lymph nodes, spleen and bone marrow
form main extracellular matrix fibres supporting hemopoietic and lymphoid tissues
reticular fibres in parenchymal organs
liver and kidney
network supporting specialised epithelial cells
type IV
sheet-like layers
meshwork
basement membrane, external laminae, lens capsule
type V
thin fibrils
basement membrane of placenta, smooth and skeletal muscle
type VI
thin fibrils
ubiquitous
type VII
short striated fibrils
anchoring fibrils in basement membrane of skin and amnion
type VIII
chains and lattices
hexagonal lattice in Descemet’s membrane in eye cornea
type IX
fibril
cartilage
type X
short chain
mineralising cartilage
type XI
fibril
cartilage
collagen structure
precursor proteins (alpha chains) wound together to form rigid linear triple helix structures, secreted by fibroblasts after proteolytic cleavage, triple helical portions are assembled into long filaments and incorporated into cross-linked fibres and bundles
fibrillar collagen
formed from 3 polypeptide (a) chains secreted with amino and carboxyl terminal extensions to prevent collagen forming inside cells
procollagen
triple helix of three polypeptide (a) chains
how do cells prevent collagen from forming inside them
secrete polypeptide (a) chains with amino and carboxyl terminal extensions
tropocollagen
formed from cleavage of terminal extensions to leave functional mid-domains
alignment of molecules
linear arrays to form long filaments
300nm long
67nm overlap/periodicity
collagen structures
collagen bundle
collagen fibre
microfibrils
via lysine residues
elastin
hydrophobic protein which assembles into filaments and sheets by cross linking
produced by fibroblasts
formation of elastic fibre
interaction of elastin and fibrillin
fibrillin organises secreted elastin to deposit it between the microfibrils to form elastic fibres
microfibrils
fibrillin is a fibril-forming glycoprotein and main component of extracellular microfibrils
constituent of elastic fibres
found in extracellular matrix of renal glomeruli (mesangium) and suspensory fibres of the lens
prominent in elastic containing matrixes
mediate adhesion between components
fibronectin
multifunctional glycoprotein
3 main forms
3 main forms of fibronectin
circulating plasma proteins
protein transiently attaching to surface of cells
insoluble fibrils forming part of matrix - dimers cross link via disulfide bonds
functional importance of fibronectin
adheres to several different tissue components
sites bind collagen and heparin, and cell adhesion molecules
extracellular structural glycoproteins
link cells to extracellular matrix via receptors
examples of extracellular structural glycoproteins
laminin, tenascin, entactin
laminin
sulfated glycoprotein
component of basement membranes
produced by most epithelial and endothelial cells
cross shaped molecule
binding sites for specific cell receptors, heparan sulfate, type IV collagen, entactin
entactin
sulfated glycoprotein
component of basement membranes
binds with laminin
link protein, binding laminin to type IV collagen
tenascin
extracellular glycoprotein
cell adhesion
embryonic tissue
cell migration in developing nervous system
integrins
class of cell adhesion molecule composed of 2 protein subunits
subunit composed of 2 protein chains with a globular head
b subunit extends through membrane and binds to actin cytoskeleton
basement membrane and external lamina
specialised sheet-like arrangements of extracellular matrix proteins and GAG - interface between parenchymal cells and support cells
what are basement membranes and external lamina associated with?
epithelial cells, muscle cells, Schwann cells
form limiting membrane around CNS
5 components of basement membrane
type IV collagen laminin heparan sulfate entactin fibronextin minor and poorly characterised protein and GAG components
what are the components of basement membrane synthesised by?
parenchymal cells - except fibronectin
3 main functions of basement membrane
adhesion interface between parenchymal cells and underlying extracellular matrix
molecular sieve
controls cell organisation and differentiation
adhesion interface between parenchymal cells and underlying extracellular matrix
cells have adhesion mechanisms to anchor them to BM
BM anchored to extracellular matrix of support tissues
adhesion interface in non-epithelial tissues
external lamina
molecular sieve
pore size depends on charge and spatial arrangement of GAG
prevents proteins leaking into tissues, protein loss from filtered blood and gaseous diffusion
cell organisation and differentiation
mutual interaction of cell surface receptors and molecules in the extracellular matrix
staining of BM
0.5mm thick and stains poorly - no H&E
faint magenta stained line with PAS due to glycoprotein
laminae of BM
lamina lucida - 60nm wide, between cell and lamina densa. lucent zone
lamina densa - dark-staining band 30-100nm thick
fibroreticular lamina - below lamina densa, merges with fibrous proteins of extracellular matrix.
3 main mechanisms by which fibroreticular lamina anchors BM to extracellular matrix
extension of lamina densa into fibroreticular lamina interacts with collagen (esp. type III)
fibrillin microfilaments link to BM and to elastic tissue in extracellular matrix
anchoring fibrils of type VII collagen link BM to matrix in skin and amnion via hemidesmosomes
types of junctions between cells and extracellular matrix
hemidesmosomes
focal contacts
laminin receptors
non-integrin glycoproteins
hemidesmosomes
anchor intermediate filament cytoskeleton to BM
focal contacts
anchor actin cytoskeleton to BM
mediated through fibronectin receptor
laminin receptors
anchor cells to BM where laminin is major component
non-integrin glycoproteins
bind to collagen and other cell matrix components
blast vs cyte
blast - cell is actively growing or secreting extracellular matrix material
cyte - quiescent phase
fibroblasts
produce fibrocollagenous tissue composed of collagen fibres associated with GAG, elastic fibres and reticular fibres
what is fibrocollagenous tissue composed of?
collagen fibres associated with GAG, elastic fibres and reticular fibres
loose fibrocollagenous tissue
collagen fibres are thin, haphazardly arranged and widely spaced
dense fibrocollagenous tissue
collagen fibres are broad and virtually confluent
what does organisation and collagen orientation depend on?
varies between sites depending on local tissue stresses
highly organised dense fibrocollagenous tissue
forms tendons and ligaments
functions of fibrocollagenous tissue
support of nerves, blood vessels and lymphatics
separation of functional layers in organs and tissues - loose, mobility and stretching
support for transient and resident immune cell populations
formation of fibrous capsule surrounding most parenchymal organs
tissue repair (fibroblasts)
myofibroblasts
aggregates of actin fibres associated with myosin - contractility
small amounts in support tissue
immunohistochemistry or ultrastructural methods
develop during repair after tissue damage
myofibroblasts in repair after tissue damage
proliferation of normally inconspicuous tissue myofibroblasts
differentiation of fibrocytes
produce collagen
retraction and shrinkage of early fibrocollagenous scar tissue
benign and malignant tumors arising from fibroblasts
fibroma
fibrosarcoma
benign and malignant tumors arising from chondrocytes
chondroma
chondrosarcoma
benign and malignant tumors arising from adipocytes
lipoma
liposarcoma
chondroblasts
produce cartilage
cartilage components
fibrous proteins (predom. type II) - mechanical stability abundant GAG - resist deformation by compressive forces
collagen fibres thin and in interwoven lattice, merges into extracellular matrix of adjacent support tissues
GAG (hyaluronic acid, chondroitin sulfate and keratan sulfate) bound to core protein aggrecan to form proteoglycan - linked to collagen lattice by link protein
staining of cartilage
H&E - blue
due to sulfated GAG
properties of cartilage
inherent turgor resisting deformation by tightly bound proteoglycans forming a hydrated matrix
small molecules diffuse freely through extracellular matrix
development of chondroblasts
from embryonic mesenchyme
appear as clusters of vacuolated rounded cells
spindle shaped cells of surrounding undifferentiated mesenchyme develops into fibroblasts
perichondrium
confining sheet of cells
structure of chondroblasts
abundant glycogen and lipid
basophilic cytoplasm - active synthesis of matrix
RER
interstital growth
proliferation of chondroblasts within established matrix
appositional growth
development of new chondroblasts from perichondrium
chondrocytes
become less metabolically active with small nuclei and pale, indistinct cytoplasm after depositing cartilage
3 types of cartilage
hyaline
fibrocartilage
elastic
hyaline cartilage
type II collagen only
forms temporary skeleton until bone in fetal development
growing point in long bones in childhood, articular surface in joints and support tissue in respiratory passages
fibrocartilage
type II and type I collagen
intervertebral disks, tendon attachments to bones and junctions between flat bones of pelvis
elastic cartilage
elastic fibres and type II collagen
auricle of ear, walls of external auditory canal and eustachian tubes, epiglottis of larynx
osteoblasts
elaborate support matrix of bone - osteoid - calcifies to form bone
osteoid
type I collagen
extracellular GAG chondroitin sulfate and keratan sulfate
sialoprotein and osteocalcin found in bone matrix and bind calcium
glycoproteins found in osteoid
sialoprotein and osteocalcin
adipocytes
intracellular storage of fat
2 types of fat storing tissue
unilocular
multilocular
uniloclar adipose tissue
white fat
develops from embryonic mesenchyme with formation of lipoblasts (spindle shaped cells) containing small fat vacuoles
lipoblasts
spindle shaped cell
spindle shaped mesenchymal cells accumulate fat in cytoplasm in multiple small vacuoles
vacuoles form larger perinuclear vacuole
maturing lipoblasts lose spindle shape
cytoplasm becomes attenuated around single lipid vacuole, nucleus displaced to one side
produces extracellular matrix material and BM forms around cell
adipocytes structure
prominent SER pinocytotic vesicles lipid biosynthesis and transport surrounded by external lamina extracellular matrix composed of reticular fibres
multilocular tissue
brown fat newborns development separate from uniloular tissue metabolises fat to produce heat lost in childhood
ultrastructure of multilocular tissue
mitochondria
lipid vacuoles
staining of multilocular tissue
eosinophilia seen histologically
brown colour seen macroscopically
why does multilocular tissue have its name?
cells contain multiple small lipid droplets
where is multilocular tissue concentrated?
support tissues in neck, shoulders, back, perirenal and para-aortic regions
2 populations of cell in multilocular tissue
lipid-rich cells with central nucleus and multiple small unstained vacuoles
polyhedral shaped cells with granular, pink stained cytoplasm, central nucleus and occasional lipid vacuoles
secretory role of adipocytes
modulate energy metabolism
influence general metabolism in coordination with hormones
secretion of proteins into blood (adipocytokines)
adipocytes function and types
secretion of proteins into blood
leptin, adipsin, resistin, adiponectin, tumor necrosis factor alpha (TNF)-alpha, plasminogen-activator inhibitor type 1
how is unilocular tissue as a support tissue and energy store?
receptors for growth hormone, insulin, glucocorticoids, thyroid hormones, norepinephrine
rich capillary blood supply and innervation by ANS
release of noradrenaline stmulates release of stored fat into blood
organisation into pads by sheets of fibrocollagenous tissue as deformable shock absorbing tissues
multilocular lobules
capillary vascular supply and thin fibrocollagenous septa divides tissue into small lobules
