Introduction

CT provides matrix that

support, physically connects
CONNECTIVE TISSUE other tissues and cells together,
major constituents and gives metabolic support to
cells as medium for diffusion
of nutrients.
ECM

consists of

Protein fibers Ground substance

• Collagen • Anionic
• Elastic fibers • Hydrophilic proteoglycans
• Glycosaminoglycans (GAGs) help stabilize the
• Multiadhesive glycoproteins ECM by binding
(laminin, fibronectin, others) to other matrix
• Water that allows the exchange components and
of nutrients and metabolic to integrins in
wastes bet. cells and the blood cell membranes
supply.

All CT originates from embryonic mesenchyme

• Tissue that develop mainly from the mesoderm.

• Consists of viscous ground substance with few collagen fibers.
• Mesenchymal cells, are undifferentiated and have large nuclei, migrate from their site of
origin in the embryo, surroundinf and penetrating developing organs.
 Cells of Connective Tissue

Fibroblasts Adipocytes Macrophages & Mononuclear Mast Cells Plasma Cells Leukocytes
Phagocyte system

• key cells in CT originating from • Fat cells found in the CT; • Filled with basophilic granules • Lymphocyte-derived, antibody- • derived from circulating blood cells
mesenchymal cells, produce and • mesenchymally derived cells • Highly developed phagocytic ability • Display metachromasia – can change producing cells – leave blood by migrating between
and specialize in turnover of protein the color of some basic dyes from blue
maintain most of the tissues EC • Specialized for cytoplasmic • Have basophilic cytoplasm rich in the endothelial cells of venules to
fibers and removal of apoptotic cells, to purple or red due to the high content
component. storage of lipid as neutral fats, or RER and a large Golgi a near the enter connective tissue
tissue debris, other particles – of acidic radicals in their sulfated GAGs
• Synthesize and secret collagen less commonly for the production • Poorly preserved by common nucleus. • increases greatly during
abundant at sites of inflammation •
(most abundant protein in of heat. fixatives, hence difficult to identify Nuclei contain compact, peripheral inflammation – a vascular and
• Adipose connective tissue – tissue • Oval or kidney-shaped nucleus
body)and elastin (both form large • Functions – release of bioactive regions of heterochromatin cellular defensive response to injury
fibers), GAGs, proteoglycans, with large population of referred to as “histiocytes”. substances for local inflammatory alternating with lighter areas of of foreign substances
multiadhesive glycoproteins. adipocytes; serves to cushion and • w/ well-developed Golgi complexes response, innate immunity, and tissue euchromatin • Inflammation:
• Fibroblast – denote the active cell insulate skin and other organs. and many lysosomes. repair: • Few plasma cells are present in - Begins with local release of
and morphologically different • Derived from monocytes circulating in a. Heparin – act as anticoagulant most CT chemical mediators from
the blood b. Histamine – promotes increased
from the quiescent fibroblasts • Average life span 10 – 20 days various cells, the ECM and
• Mononuclear phagocyte system – vascular permeability and smooth
(QF). Has more abundant blood plasma proteins
muscle contraction
cytoplasm, much RER, and well group of related cells when monocytes - These act on local blood
c. Serine proteases – activate
developed Golgi A., with large that formed in the yok sac during early various mediators of inflammation vessels, mast cells,
euchromatic nucleus and embryonic dev. Circulate and become d. Eosinophil & neutrophil factors macrophages, and other cells to
prominent nucleolus. resident in developing organs – attracts leukocytes. induce events characteristics of
• Fibrocyte – denote the QF. Smaller throughout the body. e. Cytokines – directing activities of inflammation.
than than the fibroblast, , spindle • During inflammation and tissue repair leukocytes and other immune - Ex. increased blood flow and
shaped with fewer processes, less – become activated, cells increase in system cell
vascular permeability, entry
size(in connective stroma), both by f. Phospholipid – converted to
RER, darker more heterochromatic and migration of leukocytes,
prostaglandins, leukotrienes, and
nucleus. proliferation and by recruiting and activation of macrophages
other lipid mediators of the
• Target of growth factors – additional monocytes formed in the
inflammatory response. for phagocytosis.
influence the cell growth and bone marrow. • Numerous near small blood vessels in • Function in CT for few hours or
differentiation. • Transformation from monocytes to skin and mesenteries, and in tissue that days and then undergo apoptosis
• Can be stimulated to cell divide for macrophages – increase in cell size, lines digestive and respiratory tracts.
repair of damaged organ. protein synthesis and in number of • Immediate hypersensitivity reactions
• Involved in wound healing – Golgi c and lysosomes. (IHR) – allergic reactions promoted by
myofibroblasts – well-developed • Functions: the chemical mediators stored in mast
1. Debris removal cells as they occur within a few minutes
contractile function enriched with after the appearance of an antigen.
a form of actin 2. Secrete growth factors for tissue
• Anaphylactic shock – example of IHR.
repair
Sequential events:
3. Uptake, processing, presentation a. First exposure to antigen - cause
of antigens for lymphocyte antibody-producing cells to
activation produce immunoglobulin of the
IgE class - binds avidly to receptors
on the surface of mast cells.
b. Second exposure – reacts with the
IgE on the mast cells – triggered
rapid release of histamine,
leukotrienes, chemokines &
heparin – sudden onset of the
allergic reaction
c. Degranulation of mast cells – occur
as a result of the action of the
complement molecules
participating the immunologic
reaction
• Originates from progenitor cells in the
bone marrow
 Fibers of Connective Tissue

Collagen Reticular fibers Elastic fibers

• able to form various extracellular fibers, sheets, and networks, all of which extremely strong and resistant to normal shearing • Found in delicate CT, notably in the immune system, • Thinner than type 1 collagen fibers and form sparse
and tearing forces consists of collagen type III which forms an networks interspersed with collagen bundles, esp. those
• key element of all connective tissues extensive network (reticulum) for support of many subject to regular stretching or bending.
• most abundant protein in the human body, representing 30% of its dry weight. different cells • Have rubberlike properties allowing tissue containing
• Major product of fibroblast that also secret several other cell types • Seldom visible in hematoxylin and eosin but stained these fibers to be stretched or distended
• Family if 28 collagens exists in vertebrates black with silver salts – termed argyrophilic. • Elastic lamellae – elastin as fenestrated sheets in the wall
• Category according to structures: • Also PAS positive due to high content of sugar chains of large blood vessels.
Fibrillar collagens Network or sheet-
bound to type III collagen alpha chains • Not strongly acidophilic and stain poorly with HE –
•
Linking/anchoring
• collagen types 1,2,3 forming collagens collagens Contain 10% carbohydrates stained more darkly than collagen with orcein and
• Type IV collagen
• CT1
abundant
– most
and • Have subunits
• Link fibrillar collagens to
one another and to
• Occur in the reticular lamina of basement aldehyde fuchsin.
widely distributed produced by components of the ECM membranes – surround adipocytes, smooth muscle • Composite of fibrillin – forms network of microfibrils,
collagen fibers epithelial cells and • Type VII collagen binds
• Fill the connective
are major structural type IV collagen and and nerve fibers, and small blood vessels embedded in a larger mass of cross-linked elastin
•
proteins of external anchors the basal lamina
tissue, forming
structures such as
laminae to the underlying Delicate RN serve as the supportive stroma for the • Secreted from fibroblasts
parenchymal secretory cells and rich microvascular of •
reticular lamina in
tendons, organ
basement membranes Microfibrils – act as scaffolding upon which elastin is
capsules, dermis the liver and endocrine glands. deposited – accumulates around the microfibrils and
• Collagen synthesis is a specialty of fibroblasts. • It also characterizes the stroma of hematopoietic responsible for the rubberlike property
• Procollagen alpha chains made in RER – folded as a triple helix – exocytose and cleaved to procollagen molecule (basic subunit tissue (bone marrow), the spleen, lymph nodes where • Elastic property results from the structure of the elastin
from which the fibers or sheets are assembled) – could be homotrimeric (all 3 chains identical) or heterotrimeric (2 or all 3 chains they support rapidly changing populations of subunits and the unique crosslinks holding them together
having different sequences. proliferating cells and phagocytic cells. • Have lysine-rich regions
• Bound firmly by many desmosine rings, but maintaining
the rubberlike properties of their hydrophobic domains
• Resists digestion by most proteases, but hydrolyzed by
pancreatic elastase.

• Type I collagen fibrils – produce characteristic feature by EM: transverse striations with a regular periodicity. Assemble further to
form large, extremely strong collagen fibers further bundled by linking collages and proteoglycans
• Collagen type II – present in cartilage, occurs as fibrils but does not form fibers or bundles
• Sheet forming Collagen type IV subunits – assemble as a latticelike network in epithelial basal laminae
• Collagen appear white when filled with ECM.
• Acidophilic – staining pink with eosin, blue with Mallory trichome stain, and red with Sirius red.
• A very small mesentery is used for the preparations
• Is very stable in tendons and ligaments
• Collagen turnover rate is high in periodontal ligament
• To be renewed, collagen must first be degraded initiated by enzymes collagenases – members of an enzyme class matrix metalloproteinases
(MMPs) – it clips collagen fibrils to be susceptible to further degradation by nonspecific proteases.
• MMPs secreted by macrophages, important in remodeling of ECM during tissue repair
 • Highly hydrated, transparent, complex mixture of 3 major kinds of macromolecules: GAGs, proteoglycans and
multiadhesive glycoproteins.
Ground Substance • Allows diffusion of small molecules; act as both lubricant and a barrier to the penetration of invaders
• When fixed, appears in TEM preparations as electron-dense filaments or granules

Glycosaminoglycans (GAGs) Proteoglycans Multiadhesive glycoproteins Interstitial fluid

• Long polymer of disaccharide units, usually • consist of a core protein to which are covalently attached to • Third major class of ground substance macromolecules; all have • The water in the ground substance of CT and has ion
hexosamine and uronic acid. combinations of the sulfated GAGs. multiple binding sites for cell surface integrins and for other matrix composition similar to that of blood plasma
• Hexosamine can be glucosamine or • Synthesized on RER, mature in the Golgi apparatus, where macromolecules • Contains plasma proteins of low molecular weight that pass
galactosamine, and uronic acid can be the GAG side chains are added, and secreted from cells by • Adhesive glycoproteins – allow adhesion of cells to their substrate through the thin walls of the smallest blood vessels, the
glucuronate or iduronate. exocytosis • Laminin – large trimeric glycoprotein with binding sites for capillaries
• Hyaluronan – largest and most ubiquitous • Have attached GAGs that often comprise a greater mass than integrins, type IV collagen, and specific proteoglycans, providing • One third of the body’s plasma proteins are normally found in
GAG; synthesized directly into the ECM by an the polypeptide core adhesion for epithelial and other cells. the interstitial fluid of CT
enzyme complex, hyaluronan synthase, located • Perlecan – key proteoglycan in all basal laminae • Fibronectin – with binding sites for collagens and certain GAGs, and • It is also the solvent of the metabolic waste products of the
in the cell membrane; allows molecular • Aggrecan – very large, having a core protein heavily bound forms insoluble fibrillar networks throughout connective tissue; detoxifying and excretory organs
diffusion through CT and in lubricating various with chondroitin and keratan sulfate chains. provides specific binding sites for integrins and is important both for • 2 main forces acting on the water in capillaries:
organs and joints. • Aggrecan – hyaluronan complexes – abundant in cartilage, cell adhesion and cellular migration through the ECM 1. Hydrostatic pressure of the blood caused by the
• other GAGs are synthesized in Golgi fill the space between collagen fibers and cells and contribute • Integrins – acts as matrix receptors for specific sequences on pumping action of the heart, forces water out across the
complexes: greatly to the physical properties of this tissue. laminin, fibronectin, some collagens, and certain other ECM capillary wall
1. dermatan sulfate • Decorin – with very few GAG side chains that bind the proteins; bind their ECM ligands with relatively low affinity, 2. Osmotic pressure - produced by plasma proteins such as
2. chondroitin sulfates surface of type I collagen fibrils, and syndecan, with an allowing cells to explore their environment without losing attachment albumin, which draws water back into the capillaries.
3. keratan sulfate integral membrane core protein providing an additional to it or becoming glued to it: all are heterodimers with two • Excess fluid does not accumulate in CT but drains
4. heparan sulfate attachment of ECM to cell membranes. transmembrane polypeptides: the alpha and beta chains. Note: continuously into lymphatic capillaries eventually returning to
• have high negative charge forcing GAGs to an • Embryonic mesenchyme – rich in hyaluronan and water, diversity in the subsets of integrin alpha and beta chains which cells the blood.
extended conformation an causes them to producing the characteristic wide spacing of cells and a matrix express allows cells to have different specific ECM ligands.
sequester cations – a feature that provide GAGs ideal for cell migrations and growth. • Focal adhesions – formed by clustering integrin-microfilament
with space-filling, cushioning, and lubricant • Developing and mature CT – core proteins and GAGs of complexes in fibroblast and other mesenchymal cells
functions many proteoglycans bind and sequester various growth
factors and other signaling proteins.
• Degradation of such proteoglycans during the early phase of
tissue repair releases these stored growth factors – which then
help stimulate new cell growth and ECM synthesis.
 Types of Connective Tissue

Connective Tissue Proper Reticular Tissue Mucoid Connective Tissue

• Classified as loose or dense – amount of collagen present. • Characterized by abundant fibers of type III collagen forming a • The principal component of the fetal umbilical cord – referred to as
delicate network that supports various types of cells Wharton’s jelly.
• Such collagen is also known as reticulin and is produced by modified • with abundant ground substance composed chiefly of hyaluronan
Loose (areolar tissue) Dense connective tissue
fibroblasts called reticular cells that remain associated with and • is gelatinous with sparse collagen fibers and scattered fibroblasts
o Common, forming a o Fewer cells with mostly fibroblasts partially cover the fibers. • among the fibroblastic cells – any mesenchymal stem cells – which are
layer beneath the o Clear predominance of bundled type I collagen fibers over • The loose disposition of glycosylated reticular fibers provides a being studied for their potential in regenerative medicine
epithelial lining of many ground tissue – to protect organs and strengthens them
framework with specialized microenvironments for cells in hemopoietic • similar to the tissue found in the vitreous chambers of eyes and pulp
organs and filling the tissue and some lymphoid organs (bone marrow, lymph nodes, spleen. cavities of young teeth
structurally.
spaces between fibers of • Resulting cell-lined system creates a meshwork for the passage of
muscle and nerve. Dense Irregular CT leukocytes and lymph.
o Contains: • Macrophages and dendritic cells are dispersed within these reticular
- cells, fibers, and o Bundles of collagen fibers appear interwoven, with no definite tissues to monitor cells formed there or passing through and to remove
ground substance orientation. – provides resistance to stress from all directions debris.
- Most numerous o Ex. deep dermis layer of skin and capsules surrounding most
cells are fibroblasts, organs
nerves, and small
blood vessels. Dense Regular CT
- Collagen
predominate, but o Consists mostly of type I collagen bundles and fibroblasts
elastic and reticular aligned parallel for great resistance to prolonged or repeated
fibers re also stresses from the same direction.
present o Ex.
- Moderate amount of - very strong and flexible tendons
ground substance - aponeuroses – sheetlike tendons
o Very flexible and not - ligaments – hold together components of the skeletal
very resistant to stress system
o consisting almost entirely of densely packed parallel collagen
fibers separated by very little ground substance having few
blood vessels: white in the fresh state.
o Tendinocytes – cytoplasm in this is difficult to distinguished
in H and E stained because it’s very sparse and has acidophilia
like the collagen
o Outer surface tendons and ligaments – have a layer of dense
irregular connective tissue that is continuous with the
outermost layers of the adjacent muscles and bones.
o Repair of damage in this tissue is usually low.