Topic 7
Connective Tissue
Literature
• http://www.lab.anhb.uwa.edu.au/mb140/
(notes)
• http://www.anatomyatlases.org/Microscopic
Anatomy/MicroscopicAnatomy.shtml
Connective Tissue
Connective tissue fills the spaces between organs and tissues, and
provides structural and metabolic support for other tissues and organs.
Connective tissue is made up of cells and extracellular matrix.
The extracellular matrix is made up of fibres in a protein and
polysaccharide matrix, secreted and organised by cells in the
extracellular matrix.
Variations in the composition of the extracellular matrix, determines the
properties of the connective tissue. For example, if the matrix is
calcified, it can form bone or teeth.
Specialised forms of extracellular matrix also makes up tendons,
cartilage, and the cornea of the eye.
General connective tissue is either loose, or dense, depending on the
arrangment of the fibres. The cells sit in a matrix made up of
glycoproteins, fibrous proteins and glycosoaminoglycans, which have
been secreted by the fibroblasts, and the major component of the matrix
is water.
Development
• Mesoderm
Neuroectoderm
Mucous connective tissue
• Mucous connective tissue (or mucous tissue) is a
type of connective tissue found during fetal
development. It is composed mainly of ground
substance with few cells or fibers. It can also be
referred to a group of mucoproteins found in
certain types of cysts (etc.), resembling mucus. It
is most easily found as a component of Wharton's
jelly.
• Mucous connective tissue forms the umbilical
cord.
• The vitreous of the eyeball is a similar tissue.
Mesenchyme, also called mesenchymal connective tissue, is a
type of undifferentiated loose connective tissue that is derived
mostly from mesoderm, although some is derived from other germ
layers; e.g. neural crest cells and thus originates from the ectoderm.
Most embryologists use the term "mesenchyme" only for those
cells that develop from the mesoderm.
The term mesenchyme essentially refers to the morphology of
embryonic cells, however, they do persist as stem cells into
adulthood. Mesenchymal cells are able to develop into the tissues
of the lymphatic and circulatory systems, as well as connective
tissues throughout the body, such as bone and cartilage.
Mesenchyme is characterized morphologically by a prominent
ground substance matrix containing a loose aggregate of reticular
fibrils and unspecialized cells. Mesenchymal cells can migrate
easily.
Classification
• 1. Connective tissue proper
• a. Loose Connective Tissue
• i. Areolar
• ii. Adipose
• iii. Reticular
• b. Dense Connective Tissue
• i. Dense regular
• ii. Dense irregular
2. Embryonic
3. Cartilage
4. Bone (osseous tissue)
5. Blood
http://www.highlands.edu/academics/divisions/scipe/biology/labs/rome/histology.pdf
Connective tissues contain a large amount of
non-living material referred to as the
matrix.
• fibers
• ground substance
Typically, this material is manufactured and
secreted by the cells of the specific
connective tissues.
Fibers
Fiber
Components
Location
Collagenous
Fibers
Alpha polypeptide
chains
tendon, ligament, skin,
cornea, cartilage, bone,
blood vessels, gut, and
intervertebral disc.
Elastic fibers
elastic microfibril
& elastin
extracellular matrix (blood
vessels)
Reticular fibers Type-III collagen
liver, bone marrow,
lymphatic organs
Ground substance
• Ground substance is found in all cavities and clefts between the
fibres and cells of connective tissues. Water, salts and other low
molecular substances are contained within the ground substance,
but its main structural constituent are proteoglycans.
Ground substance is soluble in most of the solvents used to
prepare histological sections and therefore not visible in ordinary
sections.
• Proteoglycans are responsible for the highly viscous character of
the ground substance. Proteoglycans consist of proteins (~5%)
and polysaccharide chains (~95%), which are covalently linked to
each other. The polysaccharide chains belong to one of the five
types of glycosaminoglycans.
• Hyaluronan (or hyaluronic acid) is the dominant
glycosaminoglycan in connective tissues. MW 1,000,000. Length
of about 2.5 µm.
• Hyaluronan serves as a "backbone" for the assembly of other
glycosaminoglycans in connective and skeletal tissue.
• The large polyanionic carbohydrates of the glycosaminoglycans
bind large amounts of water and cations.
• The bound water in the domains forms a medium for the
diffusion of substances of low molecular weight such as gases,
ions and small molecules, which can take the shortest route, for
example, from capillaries to connective tissue cells.
• Large molecules are excluded from the domains and have to find
their way through the spaces between domains.
• The restricted motility of larger molecules in the extracellular
space inhibits the spread of microorganisms through the
extracellular space. A typical bacterium ( 0.5 x 1 µm) is
essentially immobilised in the meshwork formed by the domains.
• The pathogenicity of a bacterium is indeed to some extent
determined by its ability to find its way through the mesh, and
some of the more invasive types produce the enzyme
hyaluronidase, which depolymerises hyaluronic acid.
Connective Tissue Cells
Resident cells
Fibroblasts
Adipocytes
Pigment cells
Immigrant cells
Monocytes/
histocytes/
macrophages
Plasmocytes
Mast cells
Specialised cells
Reticular cells
(reticular tissue)
Pericytes
(blood vessels)
Shwan cells
(nerve fibers)
Glial cells
(CNS)
Hondriocytes
(cartillage)
Osteocytes
(bone)
Blood cells
Fibroblasts
• Fibrocytes are the most common cell type in connective tissues.
They are the "true" connective tissue cells.
• Flattened nuclei are visible in LM sections. The cytoplasm of
inactive fibrocyte does not contain many organelles.
• Developed intermediate filaments – vimentin.
• This situation changes if the fibrocytes are stimulated.
Fibrocyte can be transformed into a fibroblast with large
amounts of the organelles which are necessary for the synthesis
and excretion of proteins.
• Fibrocytes are able to perform amoeboid movement.
• The terms fibrocyte and fibroblast refer here to the inactive
and active cells respectively - at times you will see the two
terms used as synonyms without regard for the state of activity
of the cell.
Fibroblasts
Adipocytes
• Fat cells or adipocytes are fixed cells in loose connective tissue.
Their main function is the storage of lipids. The cytoplasm
only forms a very narrow rim around a large central lipid
droplet. The flattened nucleus may be found in a slightly
thickened part of this cytoplasmic rim - if it is present in the
section, which may not be the case since the diameter of an
adipocyte (up to 100 µm).
• A "starving" adipocyte may contain multiple small lipid
droplets and gradually comes to resemble a fibrocyte.
• Lipid storage/mobilisation is under nervous (sympathetic) and
hormonal (insulin) control. Adipocytes also have an endocrine
function - they secrete the protein leptin which provides brain
centers which regulate appetite with feedback about the
bodies fat reserves.
• Adipocytes are very long-lived cells. Their number is
determined by the number of preadipocytes (or lipoblast)
generated during foetal and early postnatal development.
Adipocytes
http://www.vh.org/Providers/Textbooks/MicroscopicAnatomy/
Each adipocyte is covered with basal membrane.
Pigment cells
Melanocytes are melanin-producing
cells located in the bottom layer (the
stratum basale) of the skin's epidermis,
the middle layer of the eye (the uvea),[1]
the inner ear, meninges, bones, and
heart. Melanin is the pigment primarily
responsible for skin color.
http://en.wikipedia.org/wiki/Melanocyte
http://www.meddean.luc.edu/lumen
• The color of the melanin is dark and it absorbs all the UV-B
light and it blocks it from passing the skin layer.[6]
• Since the action spectrum of sunburn and melanogenesis
are virtually identical, they are assumed to be induced by
the same mechanism.[7] The agreement of the action
spectrum with the absorption spectrum of DNA points
towards the formation of cyclobutane pyrimidine dimers
(CPDs) - direct DNA damage.
• Once synthesised, melanin is contained in a special
organelle called a melanosome and moved along arm-like
structures called dendrites, so as to reach the keratinocytes.
Melanosomes are vesicles which package the chemical
inside a plasma membrane. The melanosomes are
organized as a cap protecting the nucleus of the
keratinocyte.
•http://www.vetmed.ufl.edu/sacs/histo/con01.htm
Monocytes/histocytes/macrophages
• A histiocyte is a tissue macrophage or a dendritic cell
(histio, diminutive of histo, meaning tissue, and cyte,
meaning cell).
• Histiocytes are derived from the bone marrow by
multiplication from a stem cell. The derived cells migrate
from the bone marrow to the blood as monocytes. They
circulate through the body and enter various organs, where
they undergo differentiation into histiocytes, which are part
of the mononuclear phagocytic system (MPS).
Histiocytes have common histological and
immunophenotypical characteristics (demonstrated by
immunostains). Their cytoplasm is eosinophilic and
contains variable amounts of lysosomes. They bear
membrane receptors for opsonins, such as IgG and the
fragment C3b of complement. They express LCAs
(leucocyte common antigens) CD45, CD14, CD33, and
CD4 (also expressed by T Helper Cells).
Macrophages and dendritic cells are derived from common bone
marrow precursor cells that have undergone different differentiation
(as histiocytes) under the influence of various environmental (tissue
location) and growth factors such as GM-CSF, TNF and IL-4. The
various categories of histocytes are distinguishable by their
morphology, phenotype, and size.
Macrophages are highly variable in size and morphology, their
cytoplasm contains numerous acid phosphatase laden lysosomes - in
relation to their specialised phagocytic function. They express CD68.
Dendritic cells have an indented (bean-shaped) nucleus and
cytoplasm with thin processes (dendritic). Their main activity is
antigen presentation; they express Factor XIIIa, CD1c, and Class II
Human leukocyte antigens.
A subset of cells differentiates into Langerhans cells; this
maturation occurs in the squamous epithelium, lymph nodes,
spleen, and bronchiolar epithelium. Langerhans cells are antigenpresenting cells but have undergone further differentiation. Skin
Langerhans cells express CD1a, as do cortical thymocytes (cells of
the cortex of the thymus gland). They also express S-100, and their
nucleus contains tennis-racket like ultra-structural inclusions
called Birbeck granules.
Mast cells
A mast cell (also known as mastocyte and labrocyte[1]) is a resident
cell of several types of tissues and contains many granules rich in
histamine and heparin. Although best known for their role in allergy
and anaphylaxis, mast cells play an important protective role as well,
being intimately involved in wound healing and defense against
pathogens.[2]
The mast cell is very similar in both appearance and function to the
basophil, a type of white blood cell. However, they are not the same, as
they arise from different cell lines.[3]
Mast cells are very similar to basophil granulocytes (a class of
white blood cells) in blood. Both are granulated cells that
contain histamine and heparin, an anticoagulant.
Both cells also release histamine upon binding to
immunoglobulin E.[3] These similarities have led many to
speculate that mast cells are basophils that have "homed in" on
tissues. Furthermore they share a common precursor in bone
marrow expressing the CD34 molecule.
Basophils leave the bone marrow already mature, whereas the
mast cell circulates in an immature form, only maturing once
in a tissue site. The site an immature mast cell settles in
probably determines its precise characteristics.[2]
Mast cells play a key role in the inflammatory process. When
activated, a mast cell rapidly releases its characteristic granules and
various hormonal mediators into the interstitium. Mast cells can be
stimulated to degranulate by direct injury (e.g. physical or chemical
[such as opioids, alcohols, and certain antibiotics such as
polymyxins]), cross-linking of Immunoglobulin E (IgE) receptors,
or by activated complement proteins.[2]
Mast cells express a high-affinity receptor (FcεRI) for the Fc region
of IgE, the least-abundant member of the antibodies. This receptor is
of such high affinity that binding of IgE molecules is essentially
irreversible. As a result, mast cells are coated with IgE, which is
produced by plasma cells (the antibody-producing cells of the
immune system). IgE molecules, like all antibodies, are specific to
one particular antigen.
http://en.wikipedia.org/wiki/Mast_cell
Plasmocytes
• Plasma B cells (also known as plasma cells, plasmocytes,
and effector B cells) are large B cells that have been
exposed to antigen and produce and secrete large amounts
of antibodies, which assist in the destruction of microbes
by binding to them and making them easier targets for
phagocytes and activation of the complement system. They
are sometimes referred to as antibody factories. An
electron micrograph of these cells reveals large amounts of
rough endoplasmic reticulum, responsible for synthesizing
the antibody, in the cell's cytoplasm. These are short lived
cells and undergo apoptosis when the inciting agent that
induced immune response is eliminated. This occurs
because of cessation of continuous exposure to various
colony-stimulating factors which is required for survival.
http://www.vh.org/Providers/Textbooks/MicroscopicAnatomy/
Loose connective tissue and dense connective tissues
These two tissues are distinguished according to the relative
amounts of fibres they contain. Dense connective tissues are
completely dominated by fibres. They are subdivided according
to the spatial arrangement of the fibres in the tissue.
In dense irregular connective tissue the fibres do not show a
clear orientation within the tissue but instead form a densely
woven three-dimensional network (dermis).
Dense connective tissue are if the fibres run parallel to each
other ( tendons, ligaments and the fasciae and aponeuroses of
muscles).
Loose connective tissue is relatively cell rich, soft and
compliant. It is also rich in vessels and nerves.
Loose connective tissue may occur in some special variants:
mucous connective tissue, reticular connective tissue and
adipose tissue.
Loose connective tissue
• Loose connective tissue is a category of connective tissue which
includes areolar tissue, reticular tissue, and adipose tissue. Loose
connective tissue is the most common type of connective tissue in
vertebrates. It holds organs in place and attaches epithelial tissue to
other underlying tissues. It also surrounds the blood vessels and
nerves. Cells called fibroblasts are widely dispersed in this tissue; they
are irregular branching cells that secrete strong fibrous proteins and
proteoglycans as an extracellular matrix. The cells of this type of
tissue are generally separated by quite some distance by a gel-like
gelatinous substance primarily made up of collagenous and elastic
fibers.
• Loose connective tissue is named based on the "hair weave" and type
of its constituent fibers..
http://en.wikipedia.org/wiki/Loose_connective_tissue
Areolar tissue
• Areolar tissue (areol(-a) being Latin for a little open space) is a
common type of connective tissue, also referred to as "loose
connective tissue". It is strong enough to bind different tissue
types together, yet soft enough to provide flexibility and
cushioning.
• It exhibits interlacing,[1] loosely organized fibers,[2] abundant
blood vessels, and significant empty space. Its fibers run in
random directions and are mostly collagenous, but elastic and
reticular fibers are also present. Areolar tissue is highly variable
in appearance.
• In many serous membranes, it appears as a loose arrangement of
collagenous and elastic fibers, scattered cells of various types;
abundant ground substance; numerous blood vessels. In the skin
and mucous membranes, it is more compact and sometimes
difficult to distinguish from dense irregular connective tissue. It
is the most widely distributed connective tissue type in
vertebrates.
The cells (dark spots within the tissue) are called fibroblasts (fibro=
fiber, blast= to make or create). These are the cells responsible for
secreting the fibers present. The larger fibers (typically pink) are called
collagen fibers. The small black fibers are elastic fibers. Collectively,
the fibers and the rest of the substance surrounding the cells would be
referred to as the matrix.
Reticular connective tissue
• Reticular connective tissue is a type of connective tissue.[1] It
has a network of reticular fibers, made of type III collagen.[2]
Reticular fibers are not unique to reticular connective tissue, but
only in this type are they dominant.[3]
• Reticular fibers are synthesized by special fibroblasts called
reticular cells. The fibers are thin branching structures.
• Reticular connective tissue is named for the reticular fibers which
are the main structural part of the tissue.
• The cells that make the reticular fibers are fibroblasts called
reticular cells. Reticular connective tissue forms a scaffolding for
other cells in several organs, such as lymph nodes and bone
marrow.
• You will never see reticular connective tissue alone--there will
always be other cells scattered among the reticular cells and
reticular fibers.
Dense irregular connective tissue
•
•
•
•
•
•
Dense irregular connective tissue (DICT) consists of a somewhat dense arrangement of
thick collagen type I fibers embedded, along with a smattering of fibroblasts, in an
amorphous ground substance.
Characteristically, dense irregular connective tissue differs from loose connective tissue in
three basic ways: The most abundant part of dense irregular connective tissue are the
collagen type I fibers, not the amorphous ground substance.
The extracellular fibers of DCT are nearly entirely collagen type I fibers.
The cells of DCT are less abundant and are virtually all fibroblasts; few other cells, if any,
are present.
Dense irregular connective tissue has an irregular, somewhat disorderly, dense weave of
thick collagen type I fibers, with bundles of fibers oriented in all directions. With its high
tensile strength, dense irregular connective tissue effectively binds various tissues together
to form organs and passively translates mechanical forces in all directions without tearing.
Unlike loose connective tissue, it is NOT a designed to be a theatre of inflammation.
Dense irregular connective tissue is found in several locations: the dermis of the skin, the
walls of large tubular organs, such as the alimentary canal, in glandular tissue, and in organ
capsules.
Dense regular connective tissue
• Tendons
• Ligaments
• Fascia
Elastic tissue
• Aorta
Tendons
http://www.umdnj.edu/~khochtah/ligament.html
http://education.vetmed.vt.edu/Curriculum/
VM8054/Labs/Lab12b/EXAMPLES/Exlasart.htm