Neurobiology 104 Read G&H chaps. 4,6.
September 25,28 2003 including pp 81-83
CONNECTIVE TISSUES
Connective tissues (C.T.) are the supporting tissues
of the body. They:
1.
physically support the body: e.g. bone and cartilage
and
literally hold the body together.
2. furnish
pathways for nerves and blood vessels, and a
compartment for exchange between capillaries and active cells.
3. provide
for immune functions, phagocytosis and wound healing.
C.T. comes in a great variety of forms, some highly
specialized,
e.g.
dentin, cementum, bone, tendon, cartilage, fat, blood.
I. Embryonic: mesenchyme
II. Adult
A. Connective tissues proper ("ordinary")
Loose
Dense
Irregular
Regular
B. Supporting
Cartilage
Bone
C. Special
Adipose
Reticular - Lymphatic
Blood
Hemopoietic
All connective tissues have important common
properties:
Their
cells are imbedded individually in extracellular matrix.
They arise
from embryonic mesenchyme.
They are
interconvertible to some extent.
Even
specialized types have intermediate forms.
Connective
tissues are categorized mainly by the physical
properties
of their extracellular components and not cells.
Ordinary Connective tissues
Ordinary connective tissues are classified as loose vs dense,
and regular vs irregular mainly on basis of their fibers.
Looser C.T. has fewer, smaller fibers; more cells;
more capillaries
and more
water.
Important examples of ordinary C.T. include:
Lamina propria - The layer of C.T. underlying an epithelium.
Dermis of
skin - leather is tanned dermis.
Stroma of organs - the framework
tissue which supports the
Parenchyma or specific active cells of
organ.
The
physical texture and durability of an organ depend
primarily on its stroma.
Adventitia of organs and fascia
between organs.
Tendons
and ligaments (and the cornea) are regular dense C.T.
Note:
Fibers can have various degrees of alignment in C.T.
but
only VERY organized C.T. is called "regular".
_______
Essential terms are bold
The 3 main structural components of ordinary C.T.
are:
collagen
fibers, elastic fibers and amorphous ground substance.
These are
synthesized by fibroblasts in
ordinary C.T.
Collagen
Collagen is a unique fibrous protein:
- the most
abundant protein of the body (and of teeth).
- very
strong: Tendons have a tensile strength
of 20,000 lbs/sq in.
-
inelastic: Wavy fibers can be
straightened but not stretched.
-
evolutionarily ancient.
-
distinctive in chemistry and structure.
Every
third amino acid is glycine.
Hydroxyproline
and hydroxylysine are almost unique to collagen.
Fibroblasts synthesize and secrete collagen as a
procollagen precursor.
Peptidases
remove the ends extracellularly to form tropocollagen.
See
G&H Fig. 4-7
Tropocollagen is a helix with three intertwisted polypeptide chains.
(2
alpha-1 and 1 alpha-2) specified by two separate genes
See
G&H Fig. 4-5
Tropocollagen chains aggregate in a staggered array
to form
a
microfibril with cross bands 640 Angstroms (64 nm) apart,
(the
hallmark of collagen in the EM).
Microfibrils aggregate into collagen fibers (~1
micron across)
Collagen fibers associate into bundles of various
thickness,
Proteoglycans bind to the surfaces of
fibrils, fibers and bundles
to
control their degree of polymerization.
Fibroblasts can deposit collagen in perfectly
parallel arrays.
They
polymerize the fibers in grooves (“coves”) in their membrane.
They also stretch masses of collagen fibers
to further align them.
At least 20 distinct types of collagen occur in
different places:
Type I is in ordinary C.T., tendons,
bone and dentin.
Type II occurs in hyaline cartilage.
Type III forms very delicate fibers
called reticular fibers.
Reticular fibers are very fine with enough carbohydrate to
stain distinctively with PAS
or silver ions.
C.T.
supported by reticular fibers is called reticular
tissue.
Type IV is found in basement
membranes. It does not form fibers.
Elastica
- is a complex rubbery material of a cross
linked globular protein.
- can have any shape; e.g. fibers, sheets and
branched strands.
- can be specially stained because it is
hydrophobic.
- complements the function of collagen by
returning stretched tissue
to its
original state.
- seriously degenerates with age.
Amorphous ground substance
(read G&H
pp 71-74)
is composed of gigantic proteoglycan molecules, with
charged linear
polysaccharides (glycosaminoglycans
= GAG's) attached to proteins.
Ground substance turns tissue fluids into extremely
viscous fluids
and gels
because the ionized polysaccharide chains are extended.
Hyaluronic acid mw ~l,000,000 produces soft gels.
Chondroitin sulfate mw ~30,000 produces hard gels (cartilage).
Keratan
sulfate and dermatin sulfate are less abundant forms.
The functions of amorphous ground substance are:
to convert
the water in tissues into a gel.
to
immobilize particles but allow diffusion of small molecules.
to
regulate the amount and composition of the aqueous compartment.
to attach
cells and collagen fibers via adhesive glycoproteins.
Adhesive
glycoproteins attach cells to the extracellular matrix.
Laminins anchor cells to basal laminae.
Fibronectin holds cells to collagen and GAG’s.
See
G&H Fig. 4-3
II: THE CELLS OF CONNECTIVE
TISSUE
Connective tissues contain a variety of cells that
may develop locally or come in from the blood. They may be fixed in place or free to wander.
Fibroblasts are the principal synthetic
cells of C.T.
They have a
spindle shape, prominent nucleus and poorly visible
cytoplasm.
Active
fibroblasts in loose C.T. have abundant cytoplasm,
large
pale nuclei, and retain the potential to divide and move.
Inactive
"fibrocytes" of dense
connective tissue appear as dark
elongate
nuclei scattered between dense bands of fibers and
probably
no longer secrete, move or divide.
Other cell
types take over the synthetic functions of fibroblasts in
specialized C.T.: smooth muscle, osteoblasts, reticular cells.
Some
fibroblasts partially develop the contractile properties of
smooth
muscle, so called myofibroblasts or myoid cells.
Adult
connective tissue encodes fixed tissue patterns.
Fibroblasts
look like their precursor mesenchymal cells but are
an
entirely different and more differentiated cell type.
The best
guess is that fibroblasts can differentiate into other
C.T.
cell types (eg adipocytes) but normally do not.
Mesenchyme or embryonic C.T.
Mesenchymal
cells look like fibroblasts but have a great range of developmental potentials.
Most fetal
mesenchymal cells have differentiated into restricted
cell
types in an adult but scattered ones remain, mostly along
capillaries and are called pericytes.
Pericytes can divide and
become
fibroblasts, adipocytes, endothelial cells, etc.
Mesenchyme
comes from mesoderm in the posterior body and from
neurocrest in the head.
C.T. cells
arise from two sources:
1. local
mesenchyme – eg fibroblasts, adipocytes.
2. via
blood from bone marrow, white blood cells, mast cells
Possibly some cells come from both sources
(i.e. osteocytes)
Macrophage (called histiocytes in ordinary C.T.):
- ingest
material by phagocytosis and pinocytosis, digest it with
lysosomes and often retain indigestibles in residual bodies.
They
also have secretory functions and roles in immunity.
- can be
nearly as abundant as fibroblasts in loose C.T.
- occur
especially where needed the most
eg under wet epithelia, in the spleen and in lymph nodes.
Histological appearances of macrophages.
Macrophages
comprise a variety of forms which vary in
appearance (and, to an unknown degree, in function).
They have
special names in various tissues.
The
appearance of a macrophage depends upon mainly what it has
ingested.
New resting
macrophages are hard to distinguish from fibroblasts
but can
be "vitally stained" by injecting dye into an animal.
Old
histiocytes often contain droplets of lipids ("foam cells").
Macrophages
are recognizable in electron micrographs by their
abundant
lysozomes and ruffled cell surface.
The life cycle of macrophages
Precursors
originate in bone marrow as monocytes.
Monocytes
travel in blood, then migrate into C.T. and
differentiate into
macrophages.
Resting
macrophages are fixed in place but become activated
and
migrate by chemotaxis during inflammation.
Senescent
macrophages can remain in C.T. for decades.
Large
indigestible particles cause macrophages to fuse into
multinucleated foreign body giant cells.
The Mononuclear Phagocyte System
(MPS)
Macrophages are best defined as the derivatives of
monocytes.
These MPS cells also share certain biochemical
commonalties.
(e.g. cell
surface receptors for antibody molecules and
lysosomal
enzymes.)
The cells of the MPS system include:
Histiocytes (in C.T.)
Free and fixed macrophages
(lymph tissue, bone marrow)
Kupffer cells (liver)
Pleural and peritoneal
macrophages (serous cavities)
Osteoclasts (bone)
Microglia (nervous tissue)
Langerhans cells (skin)
Foam cells (after
inflammation)
Giant foreign body cells
(inflammation)
The "Reticuloendothelial
System"
This is an outdated previous scheme that should be
ABANDONED.
The "RE system" would include all
phagocytic cells (except
neutrophils) together with reticular and endothelial cells.
It was based on the mistaken interpretation that
phagocytes
differentiate from reticular cells and endothelial cells as
well as
from monocytes.
Unfortunately, you will hear doc's and even
histologists speak of
"RE
cells". Let's not have any
dentists be so ignorant.
Mast cells:
- cause
inflammation, allergic symptoms and asthma.
- are packed
with secretory granules which contain
histamine, a vasodilator, and heparin,
an anticoagulant.
- accumulate
antibody molecules (IgE) on their surfaces as
receptors. They release their
granules when these antibodies
contact
their antigens, to cause familiar allergic symptoms.
- also
secrete a variety of chemicals with roles in
hypersensitivity reactions (skim through G&H pp 117-120).
- share
similarities with basophils of blood (and are sometimes
called
"tissue basophils") but are a different cell type.
- tend to
occur along blood capillaries.
Adipocytes ("unilocular fat
cells")
- are large
cells with a fat droplet and a narrow rim of cytoplasm.
- function
to store energy, insulate, produce heat and fill space.
- occur as
isolated cells, clumps, and large masses (adipose tissue).
- develop
from specialized preadipocytes or lipoblasts which resemble
fibroblasts.
Preadipocytes develop early in life and accumulate fat when
you
are old enough not to want it.
- are
surrounded by a basal lamina and supported by reticular fibers.
- are
metabolically active and complexly regulated.
Adipose tissue is highly vascular.
Human
fetuses and infants have special brown
fat.
Its
"multilocular" fat cells have many small fat droplets and
mitochondria to generate body heat.
Endothelial
cells:
- line the
entire blood vascular and lymphatic systems.
- are very
squamous with flat nuclei.
- have
great regenerative capacity.
- rest on
basal laminae which provide support and stability.
Capillaries fundamentally are components of C.T.
They
are confined to stroma (except in C.N.S.)
Endothelial cells are diverse to an unknown degree.
They do
much more than just passively line blood vessels.
In some
organs they have distinctive appearance and
specialized defensive and secretory functions.
Some
have special cell surface proteins to draw
leukocytes into the surrounding C.T. from blood.
Some
secrete chemical messengers to cause the smooth
muscle in the media of arteries to constrict.
Leukocytes = White blood cells
These cells are transient invaders into C.T.
-->ALL BLOOD LEUCOCYTES DO THEIR WORK IN C.T. AND NOT IN BLOOD.<--
Neutrophils, Eosinophils and basophils
infiltrate C.T. for
defense functions.
Neutrophils are the main phagocytes for bacteria.
The others have complex functions in
immunity.
Monocytes settle down as macrophages
in C.T.
Lymphocytes wander in large numbers
in C.T. of vulnerable
places.
B-lymphocytes can give rise to plasma
cells in C.T.
Plasma cells are factories for making antibodies
Plasma cells have much cytoplasm with basophilic rough ER.
T-lymphocytes regulate other lymphocytes in various ways.
Wait for a later lecture on blood cells.
KODACHROME
SLIDES SHOWN DURING LECTURE 1
Slide Purpose
Mucosa of lip contrast epithelium with C.T.
Mucosa vascularity of lamina propria
Skin organs embedded in C.T
Loose C.T. appearance at medium power
Dense C.T., high power contrast with loose D.T.
Tendon: dense
regular C.T.
EM of aligned collagen show how regularly collagen can be
Area of C.T. show
spectrum of loose to dense
Nerve bundles H+E show staining with H+E
Nerve, Masson stain describe Masson stain
Cornea, Masson stain dense regular C.T. with Masson stain
Large artery, H+E distinguish smooth muscle and C.T. with H+E
Artery wall elastic stain visualization of elastica
Liver, H+E appearance with H+E
Liver, Masson visibility of collagen with Masson stain
Liver, silver stain appearance of reticular fibers
Parotid gland, 0 power show stroma
Submax. gland, med power show stroma
Submax. gland, high power show stroma
KODACHROME SLIDES SHOWN DURING LECTURE 2
Fibroblast in loose C.T.
Diagram of active and inactive fibroblasts
Fibrocytes in dense C.T.
Mesenchyme from atlas
Umbilical cord mesenchyme
Diagram of a pericyte
Diagram of the dual origin of C.T. cells
Macrophage in bone marrow smear
Macrophage in lymph node
Macrophage in spleen
macrophage in lung
Loose C.T. with fibroblasts and possible
macrophages
Macrophage in C.T. spread identified by
vital staining
Medium power c.t. spread showing macrophage
+ fibroblasts
Monocyte
Table of the Monocyte Phagocyte System
The reticuloendothelial system
Tweedlee Dee's comment of the R.E. system
Mast cells in C.T. spread
Mast cells degranulated
Fat cells
Adipose tissue
Brown fat
Neutrophils in blood
Neutrophils in C.T.
Lymphocytes in blood
Lymphocytes in C.T.
Lymphocytes en masse in appendix
Plasma cells
Diagram of capillary
Capillaries in fat tissue