Connective Tissue

Departemen Biologi
Rita Maliza Ph.D
Connective tissue provides a matrix that supports and physically
connects other tissues and cells together to form the organs of the
body. The interstitial fluid of connective tissue gives metabolic support
to cells as the medium for diffusion of nutrients and waste products.

• The major constituent of connective tissue is the extracellular matrix

(ECM).
• Extracellular matrices consist of different combinations of protein
fibers (collagen and elastic fibers) and ground substance.
• Ground substance is a complex of anionic, hydrophilic proteoglycans,
glycosaminoglycans (GAGs), and multiadhesive glycoproteins
(laminin, fibronectin, and others).
The basal lamina, such
glycoproteins help
stabilize the ECM by
binding to other matrix
components and to
integrins in cell
membranes. Water within
this ground substance
allows the exchange of
nutrients and metabolic
wastes between cells and
the blood supply.
CELLS OF CONNECTIVE
TISSUE
• Fibroblasts are the key cells in connective tissue
proper .
• Fibroblasts originate locally from mesenchymal cells
and are permanent residents of connective tissue.

• Other cells found here, such as macrophages, plasma

cells, and mast cells, originate from hematopoietic stem
cells in bone marrow, circulate in the blood, and then
move into connective tissue where they function.
• These and other white blood cells (leukocytes) are
transient cells of most connective tissues, where they
perform various functions for a short period as needed
and then die by apoptosis.
 • Adipocytes (L. adeps, fat + Gr. kytos, cell), or
fat cells, are found in the connective tissue of
many organs. These large, mesenchymally
derived cells are specialized for cytoplasmic
Adipocytes storage of lipid as neutral fats, or less
commonly for the pro- duction of heat. Tissue
with a large population of adipocytes, called
adipose connective tissue, serves to cushion
and insu- late the skin and other organs.
Adipocytes have major meta- bolic significance
with considerable medical importance
HE staining of adipose tissue (a–c) and liver (d–f) of HFD-induced obesity mice after MAP treatment
(n = 6). a, e Control; b, f HFD; c, g MAP
Macrophages
& the
Mononuclear
Phagocyte
System
 Function of Macrophages

Macrophages derive from precursor cells called mono cytes circulating in the blood.
Monocytes formed in the yolk sac during early embryonic development circulate and become resident in
developing organs throughout the body, comprising a group of related cells called the mononuclear
phagocyte system.
Many of these macrophage-like cells with prominent functions in various organs have specialized names.
All are long-living cells, surviving with relative inactivity in tissues for months or years.

During inflammation and tissue repair which follow organ damage, macrophages become activated and
play a very important role.
The transformation from monocytes to macrophages in connective tissue involves increases in cell size,
increased protein synthesis, and increases in the number of Golgi complexes and lysosomes.
In addition to debris removal, macrophages secrete growth factors important for tissue repair and also
function in the uptake, processing, and presentation of antigens for lymphocyte activation, a role dis-
cussed later with the immune system.
• Fig. 1 a H&E-stained liver section 15 dpi (400×). Kupffer cell harbouring a high amount of amastigotes (arrowhead). Immature
granulomas formed by fused macrophages harbouring few amastigotes (arrows). Well-formed mature granuloma with a
complete cellular infiltrate (*). b H&E-stained liver section 35 dpi (400×). Mature functional granuloma with few fused
macrophages harbouring very few amastigotes (*). Clear granuloma without amastigotes and with presence of collagen
deposition (arrow). c H&E-stained liver section 63 dpi (400×). Clear granuloma composed mainly of lymphocytes (arrow). d
Immunohistochemical detection of Leishmania donovani antigens (400×). Immature granulomas harbouring a high amount of
amastigotes (arrows) and mature granulomas with fewer number of amastigotes (*). Scale-bars: 100 μm
 • Mast cells are oval or irregularly shaped
cells of connective tissue, between 7 and
20 μm in diameter, filled with basophilic
secretory granules that often obscure the
central nucleus.
• These granules are electron dense and of
variable size, ranging from 0.3 to 2.0 μm
in diameter.
• Because of the high content of acidic
Mast Cells radicals in their sulfated GAGs, mast cell
granules display metachromasia, which
means that they can change the color of
some basic dyes (eg, toluidine blue) from
blue to purple or red.
• The granules are poorly preserved by
common fixatives, so mast cells may be
difficult to identify in routinely prepared
slides.
Mast cells function in the localized release of many bioactive substances important in
the local inflammatory response, innate immunity, and tissue repair.

A partial list of molecules released from these cells’ secretory granules includes the
following:
■ Heparin, a sulfated GAG that acts locally as an anticoagulant
■ Histamine, which promotes increased vascular permeability and smooth muscle
contraction
■ Serine proteases, which activate various mediators of inflammation
■ Eosinophil and neutrophil chemotactic factors, which attract those leukocytes
■ Cytokines, polypeptides directing activities of leuko- cytes and other cells of the
immune system
■ Phospholipid precursors, which are converted to prostaglandins, leukotrienes, and
other important lipid mediators of the inflammatory response.
Plasma Cells • Plasma cells are lymphocyte- • The nucleus of the plasma cell is
generally spherical but eccentrically
derived, antibody-producing placed.
cells. These relatively large,
• Many of these nuclei contain
ovoid cells have basophilic compact, peripheral regions of
cytoplasm rich in RER and a heterochromatin alternating with
large Golgi apparatus near the lighter areas of euchromatin.
nucleus that may appear pale • At least a few plasma cells are
in routine histologic present in most connective tissues.
Their average life span is only 10-20
preparations days inflammation, for example,
increased blood flow and vascular
permeability, entry and migration
of leukocytes, and activation of
macrophages for phagocytosis.
• Most leukocytes function in
connective tissue only for a few
hours or days and then undergo
apoptosis.
 • The fibrous components of connective tissue are
elongated structures formed from proteins that
polymerize after secretion from fibroblasts
• The three main types of fibers include collagen,
reticular, and elastic fibers.
FIBERS • Colagen and reticular fibers are both formed by
proteins of the collagen family, and elastic fibers
are composed mainly of the protein elastin.
• These fibers are distributed unequally among the
different types of connective tissue, with the
predominant fiber type conferring most specific
tissue properties.
 • The collagens constitute a family of proteins selected during evolution for their ability to form
various extracellular fibers, sheets, and networks, all of which extremely strong and resistant to
normal shearing and tearing forces.
• Collagen is a key element of all connective tissues, as well as epithelial basement membranes and
the external laminae of muscle and nerve cells.
• Collagen is the most abundant protein in the human body, representing 30% of its dry weight. A
major product of fibroblasts, collagens are also secreted by several other cell types and are
distinguishable by their molecular composi- tions, morphologic characteristics, distribution,
functions, and pathologies. A family of 28 collagens exists in vertebrates, numbered in the order
they were identified, and the most important are listed in Table 5–3. They can be categorized
according to the structures formed by their interacting

Collagen •
•
α-chains subunits:
■ Fibrillar collagens, notably collagen types I, II, and III, have polypeptide subunits that
aggregate to form large fibrils clearly visible in the electron or light micro- scope (Figure 5–8).
Collagen type I, the most abundant and widely distributed collagen, forms large, eosinophilic
bundles usually called collagen fibers. These often densely fill the connective tissue, forming
structures such as tendons, organ capsules, and dermis.
• ■ Network or sheetforming collagens such as type IV collagen have subunits produced by
epithelial cells and are major structural proteins of external laminae and all epithelial basal
laminae.
• ■ Linking/anchoring collagens are short collagens that link fibrillar collagens to one another
(forming larger fibers) and to other components of the ECM. Type VII collagen binds type IV
collagen and anchors the basal lamina to the underlying reticular lamina in basement membranes
(see Figure 4–3).
 • Found in delicate connective tissue of many organs, notably in the immune system,
reticular fibers consist mainly of collagen type III, which forms an extensive
network (reticulum) of thin (diameter 0.5-2 μm) fibers for the support of many
different cells.
• Reticular fibers are seldom visible in hematoxylin and eosin (H&E) preparations but
are characteristically stained black after impregnation with silver salts (and are thus
termed argyrophilic (Gr. argyros, silver).
• Reticular fibers are also periodic acid–Schiff (PAS) positive, which, like
Reticular argyrophilia, is due to the high content of sugar chains bound to type III collagen α
chains. Reticular fibers contain up to 10% carbohydrate as opposed to 1% in most
other collagen fibers.
Fibers • Reticular fibers produced by fibroblasts occur in the reticular lamina of basement
membranes and typically also surround adipocytes, smooth muscle and nerve fibers,
and small blood vessels.
• Delicate reticular networks serve as the supportive stroma for the parenchymal
secretory cells and rich microvasculature of the liver and endocrine glands.
• Abundant reticular fibers also characterize the stroma of hemopoietic tissue (bone
marrow), the spleen, and lymph nodes where they support rapidly changing
populations of proliferating cells and phagocytic cells.
Elastic Fibers
• Elastic fibers are also thinner than the type I collagen fibers and form sparse networks interspersed
with collagen bundles in many organs, particularly those subject to regular stretching or bending.
• As the name implies, elastic fibers have rubberlike properties that allow tissue containing these
fibers, such as the stroma of the lungs, to be stretched or distended and return to their original
shape.
• In the wall of large blood vessels, especially arteries, elastin also occurs as fenestrated sheets called
elastic lamellae.
• Elastic fibers and lamellae are not strongly acidophilic and stain poorly with H&E; they are stained
more darkly than collagen with other stains such as orcein and aldehyde fuchsin.
• Elastic fibers (and lamellae) are a composite of fibrillin (350 kDa), which forms a network of
microfibrils, embedded in a larger mass of cross-linked elastin (60 kDa).
• Both proteins are secreted from fibroblasts (and smooth muscle cells in vascular walls) and give
rise to elastic fibers.
• Initially, microfibrils with diameters of 10 nm form from fibrillin and various glycoproteins.
• The microfibrils act as scaffolding upon which elastin is then deposited.
• Elastin accumulates around the microfibrils, eventually making up most of the elastic fiber, and is
responsible for the rubberlike property.
 • The ground substance of the ECM is a highly
hydrated (with much bound water),
transparent, complex mixture of three major
GROUND kinds of macromolecules: glycosaminoglycans
(GAGs), proteoglycans, and multiadhesive
SUBSTANCE glycoproteins.
• Filling the space between cells and fibers in
connective tissue, ground substance allows
diffusion of small molecules and, because it is
viscous, acts as both a lubricant and a barrier
to the penetration of invaders.
Thank you