CONNECTIVE TISSUE

Functions of Connective Tissue

Structural support (capsules, bone, cartilage)

Nutrition
Defense (non-specific and immune)
Cell growth and differentiation
Cell migration
Insulation

Connective Tissues: Special

Characteristics

Common embryological origin (from

mesoderm)
Innervated and Vascular (direct blood supply)

Cartilage is the one exception with no capillary beds

Extracellular Matrix
ground substance (gelatinous glycoproteins)
structural fibers (fibrous proteins, e.g., collagen, elastin,
reticulin)

Types of Connective Tissues

Connective Tissue Proper

areolar (loose fibrous) connective tissue
adipose tissue
reticular connective tissue
dense (fibrous) regular connective tissue
dense (fibrous) irregular connective tissue
Cartilage
hyaline cartilage
elastic cartilage
fibrocartilage
Bone
Blood

Types of Connective Tissue

gelatinous

mineralized

liquid

Classified by the
characteristics of the matrix

Connective Tissue Elements

Ground substance

supports cells, binds them together

may be solid, fluid or gel
Componets:

Interstitial Fluid

Cell Adhesion ProteinsFibronectin, laminin and others

Serve as connective tissue glue

Connective Tissue Elements

Proteoglycans - large polysaccharide molecules bound

to a protein core (like a bottle brush)
Glycosaminoglycans (GAGs) are attached to
proteoglycans

They trap water. As GAGs increase, so does viscosity

hyaluronic acid gelatinous, separates cells, traps
extracellular fluid; lubricates joints; gives shape to eyeballs;
fills body spaces
chondroitin sulfate capable of being mineralized; cartilage,
bones, skin, blood vessels
dermatin sulfate harder; skin, tendons, blood vessels, heart
valves
keratin sulfate - still harder; bone, cartilage, cornea of the
eyes

Connective Tissue Elements

Fibers

Proteins that are embedded in the ground substance

Provide structural support, adhesion, connect cells
Collagen

tough; provides high tensile strength

Also called white fibers
highly polymerized, gigantic molecules
tough, moderate flexibility
bone, cartilage, tendons, ligaments

elastic fibers = elastin

branched; smaller, thinner fibers than collagen

very flexible and elastic but also strong
can be stretched to 150% of its original length
Also called yellow fibers

Connective Tissue Elements

reticular fibers

branched collagenous fibers that form delicate networks

thin, less polymerized collagen fibers

elastic & reticular fibers require special stains to be

seen in the light microscope

Connective Tissue Elements

Cells fewer, rarely touching, surrounded by

a matrix

immature forms (-blasts) secrete the matrix and can

still divide
once the matrix is secreted, the cells mature into cytes which have decreased cell divisions and secrete
less matrix material
chondro- cartilage, osteo- bone, fibro connective,
etc. Fibroblasts connective tissue proper
Chondroblasts cartilage
Osteoblasts bone
Hematopoietic stem cells blood
White blood cells, plasma cells, macrophages, and
mast cells

Connective Tissue Structure

Connective tissue
Fibers

Fibers

Long, rope-like protein extracellular

polymers
Present in variable proportions in the
different types of connective tissues
Three types: collagen, reticular and
elastic fibers. Collagen and reticular
fibers are composed of various types of
collagen, elastic fibers are composed
mainly of elastin

Collagen fibers

Collagens are the most abundant proteins

in the body.
There are many types of collagen that
differ in their origin, chemical composition,
functions, distribution and pathology

Collagen biosynthesis

Collagen biosynthesis

Collagen biosynthesis

Collagen fibrils
TRIPLE HELIX
2 x alpha1 + 1x alpha2

1,5 nm

Collagen fibrils

Collagen fibrils, TEM

Collagen types

Fibril-forming collagen: types I, II, III, V

and XI
Fibril-associated collagen: types IX and XII
Network-forming collagen: type IV
Anchoring collagen: type VII

Collagen types

Collagen I

Collagen II

2 x a1 + a2 or 3 x a1
Forms fibrils, the most resistant to mechanical
tension
In: skin, bone, tendons, connective tissue
capsules
3 x a(II)1
Forms fibrils
In hyaline and elastic cartilage

Collagen IV

3 x a(IV)1 or 3 x a(IV)2
Forms a network in the basal laminae

Elastic fibers

Isolated, thin fibers or arranged in

networks
Localised in lung, urinary bladder, skin,
aorta and elastic cartilage
Special staining : orcein

Elastic fibers

Elastin molecules are joined by covalent

bonds to generate an extensive crosslinked network.
Because each elastin molecule in the
network can expand and contract like a
random coil, the entire network can
stretch and recoil like a rubber band. )

Elastic fibers

RETICULAR FIBERS

Thin fibers, forming networks

Distribution : liver, spleen, lymph nodes,
haematopoietic organs
Special staining : silver impregnation

Connective tissue
Elements:

Ground substance
Fibers
Cells

Extracellular matrix

Ground substance

Composed of glycoproteins and

proteoglycans
Participates to binding cells to fibers
Colorless and transparent in usual stains
Viscous

Ground substance

Fibronectin (homodimer) binds cells, collagen

and GAG

Laminin (heterotrimer) mediates attachment

of epithelial cells to basal laminae

Cells have membrane receptors, integrins, that
bind collagen, fibrinectin, laminin and other
extracellular structural components
Integrins are also attached to the cytoskeleton
(actin fibers)

Ground substance

Proteoglycans (PG) = proteic core +

glycosaminoglycans (GAG)
GAG are linear polysaccharides composed
of repetitive disaccharide units
Disaccharide units =
uronic acid + hexosamine
Glucuronic ac. Glucosamine
Iduronic ac.
Galactosamine

Ground Substance: Proteoglycan

Structure

Ground substance

Except hyaluronic acid, GAG are part of PG

PG are intensly hydrophilic polyanions
They bind cations (Na+) thus attracting
water they regulate consistency of
connective tissue
GAG examples: dermatan sulfate,
chondroitin sulfate, keratan sulfate,
heparan sulfate

Ground substance

Structural glycoproteins (GP) are

glycosilated proteins branched
oligosaccharide moieties
GP mediate adhesion of cells to
extracellular matrix components

Ground substance

Fibronectin (homodimer) binds cells, collagen

and GAG

Laminin (heterotrimer) mediates attachment

of epithelial cells to basal laminae

Cells have membrane receptors, integrins, that
bind collagen, fibrinectin, laminin and other
extracellular structural components
Integrins are also attached to the cytoskeleton
(actin fibers)

The molecular structure of

proteoglycans and glycoproteins.

A: Proteoglycans contain a core of

protein (vertical rod in drawing) to
which molecules of glycosaminoglycans
(GAGs) are covalently bound. A GAG is
an unbranched polysaccharide made up
of repeating disaccharides; one
component is an amino sugar, and the
other is uronic acid. Proteoglycans
contain a greater amount of
carbohydrate than do glycoproteins.
B: Glycoproteins are globular protein
molecules to which branched chains of
monosaccharides are covalently
attached.

Schematic diagram of cell-surface

synedcan proteoglycan. The core protein
spans the plasma membrane through the
cytoplasmic domain. The syndecan
proteoglycans possess 3 heparan sulfate
chains and sometimes chondroitin sulfate.

A: The structure of fibronectin.

Fibronectin is a dimer bound by SS
groups, formed by serially disposed
coiled sites, that bind to type I
collagen, heparan sulfate, other
proteoglycans, and cell membrane
receptors.
B: The structure of laminin, which is
formed by 3 intertwined polypeptides
in the shape of a cross. The figure
shows sites on the molecule with a
high affinity for cell membrane
receptors and type IV collagen and
heparan sulfate, which are components
of basal laminae. Laminin thus
promotes adhesion of cells to basal
laminae.

Integrin cell-surface matrix

receptor. By binding to a
matrix protein and to the
actin cytoskeleton (via
alpha-actinin) inside the
cell, the integrin serves as
a transmembrane link. The
molecule is a heterodimer,
with alpha and beta chains.
The head portion may
protrude some 20 nm from
the surface of the cell
membrane into the
extracellular matrix.

Connective
Tissue
Cells

Connective tissue cells

classification

Proper to CT (fixed cells)

- fibroblast - fibrocyte (condro-, osteo-)
- adipocyte (uni-, multilocular)
- reticular cells

Migrated (mobile cells)

-

granulocytes
B and T lymphocytes
macrophages
mastocyte
melanocyte

Connective tissue cells

classification

Cells that produce/degrade the extracellular

matrix

Metabolic cells

fibroblasts, osteoblasts, condroblasts, macrophages

adipocytes

Defense (specific/non-specific)

Lymphocytes, macrophages, neutrophils

Fibroblast

The most frequent cell

Fibers (collagen, reticulin & elastic) and
ECM components synthesis
Elongated cells, 20 mm, branched
processes, basophilic cytoplasm, oval ,
euchromatic nucleus, 1 or 2 nucleoli

Fibroblasts, fibrocytes

Fibroblast
Produces:
Elements of the extracellular matrix:
procollagen, proelastin, fibrillin, GAG, PG
and GP;
Enzymes: matrix metalloproteinases collagenase (degrades collagen at neutral
pH), elastase;
Growth factors

Fibroblast
Properties:
Ability to switch its fenotype
fibroblast fibrocyte
Can change shape
Mobile
Induces differentiation of surrounding cells

Fibrocyte

Less active than fibroblasts: smaller, lesser

cytoplasm, a few short unbranched
processes
Eosinophilic cytoplasm
Elongated and heterochromatic nucleus

Unilocular (white) adipocyte

Round (when isolated) or polygonal in

groups
One large lipid droplet (inclusion)
A thin rim of cytoplasm at the periphery
that contains a flattened, heterochromatic
nucleus (signet ring)

Multilocular (brown) adipocyte

Smaller cells
Many smaller lipid droplets in the
cytoplasm foamy look
Round, central nucleus
Mostly found before birth and in neonates
Role in thermogenesis

Reticular cells

Variable functions but similar morpholgy;

some contribute to forming the stroma of
lymphoid and hematopoietic organs
Star-shaped cells with long and thin
processes that establish anchoring
junctions with neighboring cells; round,
central, pale nucleus, larger than nuclei
surrounding it

Cytoreticule
Cytoreticule =
Reticular cells
+
Reticular fibers

Melanocytes

Cell of ectodermal origin

Consequently migrates to dermis, epidermis,
iris, hair root
Snowflake-shaped cell, with many branched
processes; 30 mm
Melanin granules in the cytoplasm, darkbrown;
Round, central, small nucleus

Melanocytes

Melanosomes visible in EM:

Primary melanosomes are Golgi vesicles that

accumulate thyrosin (the melanin precursor) and
thyrosinase, located at the base of cell processes
Secondary melanosomes are heterogenous
vesicles (EM) that accumulate melanin
Tretiary melanosomes are found at the tips of the
cell processes; they are released from
melanocytes and engulfed by surrounding cells
(keratinocytes)

Macrophages

Derived from peripheral blood monocytes,

Involved in phagocytosis and inflamatory
response
A family of cells with various shapes,
localisations and names:

Histiocytes: connective tissue

Kupfer cells: liver
Alveolary macrophages: lung
Osteoclasts: bone
Microglia: central nervous system

Macrophages

Grouped as the mononuclear phagocytic

system
Macrophages of the connective tissue:
about 30 mm, ruffled membrane,
acidophilic lysosomes in the cytoplasm,
can have various heterogenous
inclusions ingested material
Round, oval or kidney-shaped nucleus,
excentrical, can have nucleoli

Macrophage

Main function: phagocytosis

Triggered by a specific interaction
between membrane receptors and ligands.
Consequences:

Cell movement towards target particle

Pseudopodae formation engulfment
Respiratory burst
Secretion: cytokines, interferons, complement
& coagulation factors
Production of matrix metalloproteinases

Macrophage, TEM

Mast cells

Localized in most of the loose

connective tissue areas, along blood
vessels
Oval cell, 20-30 mm
Cytoplasm has numerous basophilic,
metachromatic granules, 0,1-1 mm.
Pseudopodae in EM.
Round, small and central nucleus

Mast cells

Granules contain heparin or chondroitin

sulfate, histamin, Eosinophil Chemotactic
Factor, etc.
The content can be released out of the cell degranulation. The process is triggered by
chemical, physical stimuli, or through
binding of antigen-IgE complexes by
specialized receeptors
Degranulation is mediated by cAMP and
leads also to leukotriene synthesis

Mast cell degranulation

Mast cells, Toluidin blue stain

Mast cell, TEM

Plasma cells

Found in lymphoid organs (lymph nodes,

spleen, bine marrow) and connective tissues
associated to the respiratory and digestive
mucosae
Originate in B lymphocytes, that are terminaly
differentiated as a response to antigen
challenge
Secrete immunoglobulins (antibodies): IgM,
IgG, IgA, IgE

Plasma cells

Oval cell, 20 mm
Basophilic cytoplasm (due to abundant
RER), with a perinuclear pale area
(Golgi apparatus); can contain
acidophilic Russel bodies (secretory
granules)
Excentric nucleus, with hetero- and
euchromatin in a characteristic pattern:
spokes and barrel, clockface. Visible
nucleolus

Plasma cell

Plasma cell, TEM

Plasma cells, TB stain

Lymphocytes

T and B subpopulations
Central role in the immune response,
migrated from the blood stream
Small round cells (10 mm), with a round
and dark-staining nucleus and a few
basophilic cytoplasm

Neutrophils

Migrated from the blood stream, role in

phagocytosis (microphage)
Eosinophilic cytoplasm with small granules
Characteristic nucleus: heterochromatic,
2-5 lobes