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Prepared by:-Dr. Alazar. E May/2023
Connective &
Supporting Tissue
I. Overview
- formed primarily of ECM in which various types of cells are embedded.
- functions:
•provides structural (mechanical ) support for organs and
cells.
• serves as a medium for exchange of nutrients and wastes
between the blood and tissues
( transport of nutrients and metabolites).
• aids in protection against micro organisms and in repair of
damage tissues (physical & immunological defense)
• provides a site for storage of fat ( reserve energy storage).
• heat generation (brown fat),
• haemopoiesis (blood cell formation).
☞ BINDING TOGETHER: framework
☞ COMPARTMENTALIZATION
• Structurally, connective tissue (CT) is formed by :
• cells
• fibers
• ground substance.
• Unlike the other tissues (epithelium, muscle, and nerve),
which are formed mainly by cells,
• major constituent of CT is extracellular matrix (ECM).
• ECM consist of different combinations of protein fibers
(collagen, reticular, and elastic) and ground substance.
Fibers, predominantly composed of collagen, constitute
• tendons,
• aponeuroses,
• capsules of organs, and
• membranes that envelop the CNS (meninges).
• They also make up the trabeculae and walls inside
several organs, forming the most resistant component
of the stroma, or supporting tissue of organs.
responsible for the remarkable structural,
functional, and pathologic diversity of CT.
➽ Embryologic origin: mesenchyme (mesoderm), except head mesenchyme (neural crest)
(unlike most epithelial tissue which is derived from ectoderm and endoderm).
II. Extracellular matrix
- consists of ground substance, fibers, and tissue fluid.
- provides a medium for the transfer of nutrients and waste
materials between CT cells and the bloodstream.
A. Ground substance (intercellular )
- is a highly hydrated, colorless, transparent, gel-like material that
fills the space between the cells and fibers of CT (structural
function). (In ordinary CT, it consists mainly of water).
- is a complex mixture of • glycosaminoglycans (GAGs),
• proteoglycans, and
• glycoproteins.
- acts as a lubricant and helps prevent the penetration of
tissues by foreign particles.
Ground substance may be highly modified in the special forms of CT.
• In blood, the ground substance lacks stabilizing macromolecules.
We call this free-flowing ground substance plasma.
• In skeletal tissue, the ground substance may become mineralized by
deposition of calcium salts. We call this rigid ground substance bone.
• In cartilage, the ground substance is much more solid than in ordinary
CT but still retains more resiliency than bone.
●Ground substance is a highly hydrophilic, viscous complex
of anionic macromolecules (glycosaminoglycans and
proteoglycans) and multiadhesive glycoproteins (laminin,
fibronectin, …) that impart strength and rigidity to the
matrix by binding to receptor proteins (integrins) on the
surface of cells and to the other matrix components.
●the molecules of CT serve other important biological functions,
such as serving as a reservoir for hormones controlling
cell growth and differentiation.
● The hydrated nature of much CT matrix is also the medium
through which nutrients and metabolic wastes are
exchanged between cells and their blood supply.
● Ground substance is found in all cavities and clefts between
the fibres and cells of CT.
●Water, salts and other low molecular substances are contained
within the ground substance, but its main structural
constituent are proteoglycans.
• Collagen and reticular fibers are formed by the protein collagen
• Elastic fibers are composed mainly of the protein elastin.
• These fibers are distributed unequally among the types of CT.
• Actually, there are two systems of fibers:
• collagen system, consisting of collagen and
reticular fibers, and
• elastic system, consisting of the elastic,
elaunin, and oxytalan fibers.
• In many cases, the predominant fiber type is responsible for
conferring specific properties on the tissue.
B. Fibers
- are long, slender protein polymers.
- include:
• collagen fibers
• reticular fibers
• elastic fibers
- are present in different proportions.
1. Collagen fibers
– most abundant protein in the human body, representing
30% of its dry weight.
– More than 20 types
– Produced by fibroblast
– are composed of type I collagen, which consists of many
closely packed tropocollagen fibrils.
– have great tensile strength and impart both flexibility
and strength to tissues containing them.
– are present in bone, skin, cartilage, tendon, basal lamina,
smooth muscle
– produced by fibroblasts.
– are produced in a two-stage process involving
• intracellular events (in fibroblasts) and
• extracellular events.
1• Collagens That Form Long Fibrils
• The molecules of long fibril–forming collagens aggregate to form fibrils clearly
visible in the electron microscope.
• These are collagen types I, II, III, V, and XI.
• Collagen type I is the most abundant and has a widespread distribution.
►It occurs in tissues as structures that are classically designated as
collagen fibers and that form structures such as
• bones
• dentin
• tendons
• organ capsules
• dermis.
2• Fibril-Associated Collagens
• are short structures that bind collagen fibrils to one another and to other
components of the ECM. ►They are collagen types IX, XII, and XIV.
3• Collagens That Form Networks (type IV collagen)
• The molecules of network-forming collagen, assemble in a meshwork that
constitutes the structural component of the basal lamina.
4• Collagens That Form Anchoring Fibrils (type VII collagen)
• is present in the anchoring fibrils that bind collagen fibers to the basal lamina.
Scars are made of collagen.
Types of Collagen
Collagen synthesis, an activity originally believed to be restricted to fibroblasts,
chondroblasts, osteoblasts, and odontoblasts, has now been shown to be
widespread, with many cell types producing this protein.
• The principal AAs that make up collagen are glycine (33.5%),
proline (12%), and
hydroxyproline (10%).
• The protein unit that polymerizes to form collagen fibrils is the elongated molecule called
tropocollagen.
• Tropocollagen consists of three subunit polypeptide chains intertwined in a triple helix.
• In collagen types I, II, and III,
– tropocollagen molecules aggregate into microfibrillar subunits that are packed together to form fibrils.
• Hydrogen bonds and hydrophobic interactions are important in the aggregation
and packing of these units.
• In a subsequent step, this structure is reinforced by the formation of covalent cross
links, a process catalyzed by the activity of the enzyme lysyl oxidase.
• In collagen types I and III, these fibrils associate to form fibers.
• (In type I, the fibers can associate to form bundles
• type II (present in cartilage) occurs as fibrils but does not form fibers or bundles).
• Collagen type IV, present in all basement membranes, does not form either fibrils or fibers.
Biosynthesis of Collagen Type I
1. Polypeptide achains are assembled on polyribosomes bound to RER membranes and
injected into the cisternae as preprocollagen molecules.
●The signal peptide is clipped off, forming procollagen.
2. Hydroxylation of proline and lysine occurs after these AAs are incorporated into polypeptide
chains.
● Hydroxylation begins after the peptide chain has reached a certain minimum length
and is still bound to the ribosomes.
● enzymes involved are peptidyl proline hydroxylase and peptidyl lysine hydroxylase.
3. Glycosylation of hydroxylysine occurs after its hydroxylation.
● Different collagen types have different amounts of carbohydrate in the form of galactose
or glycosylgalactose linked to hydroxylysine.
4. Each chain is synthesized with an extra length of peptides called registration peptides on
both the amino-terminal and carboxyl-terminal end.
● extra peptides make the resulting procollagen molecule soluble and prevent its
premature intracellular assembly and precipitation as collagen fibrils.
● Procollagen is transported as such out of the cell to the extracellular environment.
5. Outside the cell, procollagen peptidases (protease) remove the registration peptides.
● altered protein (tropocollagen) is able to assemble into polymeric collagen fibrils.
● hydroxyproline residues contribute to the stability of the tropocollagen triple helix,
forming hydrogen bonds between its polypeptide chains.
6. Collagen fibrils aggregate spontaneously to form fibers.
● Proteoglycans and structural glycoproteins play an important role in the aggregation
of tropocollagen to form fibrils and in the formation of fibers from fibrils.
7. The fibrillar structure is reinforced by the formation of covalent cross-links between
tropocollagen molecules.
● This process is catalyzed by the action of the enzyme lysyl oxidase, which also
acts in the extracellular space.
Collagen synthesis.
The assembly of the triple helix
and the hydroxylation and
glycosylation of procollagen
molecules are simultaneous
processes that begin as soon
as the three chains cross the
membrane of the RER.
The aggregation of mature
collagen molecules
(tropocollagen) into fibrils occurs
in the extracellular environment.
Because collagen
synthesis depends
on the expression of
several genes and
on several
posttranslation
events, many
collagen diseases
have been described.
MEDICAL APPLICATION
Collagen synthesis depends on the expression of several genes and several posttranslational events.
Pathological conditions are directly attributable to insufficient or abnormal collagen synthesis.
Certain mutations in the α1 (I) or α 2 (I) genes lead to osteogenesis imperfecta.
●Many cases of osteogenesis imperfecta : due to deletions of all or part of the α 1 (I) gene.
(However, a single AA change is sufficient to cause certain forms of this disease,
particularly mutations involving glycine).
● Glycine must be at every third position for the collagen triple helix to form.
Other diseases that result from an overaccumulation of collagen.
● progressive systemic sclerosis
● almost all organs present an excessive accumulation of collagen (fibrosis).
● in the skin, digestive tract, muscles, and kidneys, causing hardening and
functional impairment of the implicated organs.
● Keloid is a local swelling caused by abnormal amounts of collagen that
form in scars of the skin.
(Keloids, which occur most often in individuals of black African descent
can be a troublesome clinical problem to manage; not only can they be
disfiguring, but excision is almost always followed by recurrence).
● Vitamin C (ascorbic acid) deficiency leads to scurvy(degeneration of CT).
● Without this vitamin, fibroblasts synthesize defective collagen, and the
defective fibers are not replaced.
This process leads to a general degeneration of CT that becomes more
pronounced in areas in which collagen renewal takes place at a faster rate
The periodontal ligament that holds teeth in their sockets has a relatively high
collagen turnover; consequently, this ligament is markedly affected by
scurvy, which leads to a loss of teeth.
Ascorbic acid is a cofactor for proline hydroxylase(essential for collagen synthesis
2. Reticular fibers (rete, net)
- are extremely thin formed of loosely packed tropocollagen fibrils.
- are composed primarily of type III collagen
- Reticular fibers form thin supporting networks
- constitute the architectural framework for
- hematopoietic organs (eg, spleen, lymph nodes, red bone
marrow) and endocrine glands.
- Endoneurium
- Found in basement membrane
-create a flexible network in organs that are subjected to changes in form
or volume, such as the
► arteries
► liver
► uterus
► intestinal muscle layers
3. Elastic fibers
- are coiled, branched fibers
- are composed of microfibrils of elastin and fibrillin
- may be stretched up to 150% of their resting length.
- Function
- add resilience to CT
- Maintain extensible organs(organs that requires ability to expand )
- Distributions
- Larynx, Trachea, bronchi, bronchioles, & Inter-alveolar septa
- Elastic arteries, Elastic cartilage, vocal ligaments
- Skin
- ligamenta flava of the vertebral column, ligamenta nuchae of neck
MEDICAL APPLICATION
Fibrillin is a family of proteins related to the
scaffolding necessary for the deposition of elastin.
Mutations in the fibrillin gene result in Marfan
syndrome, a disease characterized by a lack of
resistance in the tissues rich in elastic fibers.
Because the large arteries are rich in components of
the elastic system and because the blood
pressure is high in the aorta, patients with this
disease often experience aortic rupture, a life-
threatening condition.
Glycosaminoglycans (GAGs; originally called acid
Muco-polysaccharides)
• are linear polysaccharides formed by repeating
disaccharide units usually composed of
► uronic acid (glucuronic or iduronic acid) &
► hexosamine (glucosamine or galactosamine
)
• With the exception of hyaluronic acid, these linear
chains are bound covalently to a protein core,
forming a proteoglycan molecule.
• Because of the abundance of hydroxyl, carboxyl, and
sulfate groups in the carbohydrate moiety of most
GAGs, these molecules are intensely hydrophilic
and act as poly-anions.
• With the exception of hyaluronic acid, all other GAGs
●GAGs attach via core- and link-proteins to a backbone formed by the
hyaluronic acid.
● The coiled arrangement of the Hyaluronan and other attached GAGs fills a
roughly spherical space with a diameter of ~0.5 µm.
This space is called a domain.
Neighboring domains overlap and form a more or less continuous
3D molecular sieve in the interstitial spaces of the CTs.
● The large poly-anionic carbohydrates of the GAGs bind large
amounts of water and cations.
● The bound water in the domains forms a medium for the diffusion of
substances of LMW such as gases, ions and small molecules,
which can take the shortest route, for example, from capillaries to CT 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 immobilized 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 depolymerizes hyaluronic acid.
Hyaluronan (or hyaluronic acid) is the dominant GAG in CT.
. serves as a "backbone" for the assembly of other GAGs
in connective and skeletal tissue, which results in
even larger molecule complexes
●Hyaluronan is also a major component of the
● synovial fluid (fills joint cavities)
● vitreous body of the eye
● The remaining four major GAGs are
Chondroitin sulfate
Dermatan sulfate
Keratan sulfate
Heparan sulfate
Schematic diagram of cell-surface
syndecan proteoglycan.
The core protein spans the plasma
membrane through the cytoplasmic
domain.
The syndecan proteoglycans possess
three heparan sulfate chains and
sometimes chondroitin sulfate.
•
The molecular structure of
proteoglycans & glycoproteins.
A: Proteoglycans contain a core of protein (vertical
rod in drawing) to which molecules of
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.
In general the three-dimensional structure of
proteoglycans can be pictured as a test tube brush,
with the wire stem representing the core protein and
the bristles representing the sulfated GAGs.
Proteoglycans contain a greater amount of
carbohydrate than do glycoproteins.
core protein
GAGs
(wire stem)
(bristles)
B: Glycoproteins are globular protein molecules to which branched
chains of monosaccharides are covalently attached.
Their polypeptide content is greater than their polysaccharide content.
Hypothyroidism – accumulation of excess GAGs
(myxedema).
Proteoglycans
● are responsible for the highly viscous character of the ground substance.
● 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 GAGs, which
form the bulk of the polysaccharides in the ground substance.
(Because of these characteristics, proteoglycans can bind to a great
number of cations (usually sodium) by electrostatic (ionic) bonds.
● are intensely hydrated structures with a thick layer of solvation water
surrounding the molecule.
[When fully hydrated, proteoglycans fill a much larger volume than
they do in their anhydrous state and are highly viscous].
●are composed of a core protein associated with the four main GAGs:
dermatan sulfate, chondroitin sulfate, keratan sulfate, and
heparan sulfate.
● are three-dimensional structures that can be pictured as a test tube
brush, with the wire stem representing the protein core and the
bristles representing the GAGs.
●are compounds that contain a protein moiety to which carbohydrates
are attached.
● In contrast to proteoglycans, the protein moiety usually
predominates, and these molecules do not contain the
linear polysaccharides formed by repeating
disaccharides containing hexosamines.
● Instead, the carbohydrate moiety of glycoproteins is frequently a
branched structure.
● Several glycoproteins have been isolated from CT, and they play an
important role: interaction between neighboring adult and
embryonic cells & adhesion of cells to their substrate.
● Fibronectin (L. fibra, fiber, + nexus, interconnection)
is a glycoprotein synthesized by fibroblasts and
some epithelial cells and has binding sites for cells, collagen, and
GAGs. (Fibronectin is distributed as a network in the intercellular
spaces of many tissues).
Interactions at these sites help to mediate normal cell adhesion
and migration.
● Laminin is a large glycoprotein that participates in adhesion of
epithelial cells to the basal lamina, a structure rich in laminin.
Glycoproteins (Multiadhesive glycoproteins)
B: The structure of laminin, which is formed by three 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.
A: The structure of fibronectin.
Fibronectin is a dimer bound by S–S groups,
formed by serially disposed coiled sites, that
bind to type I collagen, heparan sulfate, other
proteoglycans, and cell membrane receptors.
Classification of Connective
Tissue
Types of CT
CT Proper
loose CT
areolar
adipose
Reticular
Elastic
Dense CT
regular
irregular
Supporting CT
Cartilage
hyaline
fibrocartila
ge
Elastic
Bone
Compact
Spongy
Fluid CT
Blood
lymph
Connective Tissue Proper
A. Loose CT
 Also called Areolar Tissue which refers to tissue that
contains interstitial space.
 possesses fewer cells and fibers
 More ground substance than dense CT
 Three main types of loose CT
1. Adipose tissue
2. Reticular tissue
3. Elastic tissue
Loose CT
• 1. Adipose tissue
– is the primary site for storage of energy (in the form of
triglycerides).
– has a rich neurovascular supply.
– Insulates organ, acts as cushion
– Located throughout the body
• 2 types
A. White adipose tissue
– is composed of unilocular adipose cells.
– constitutes almost all the adipose tissue in adults and
is found throughout the body.
– stores and releases lipids
B. Brown adipose tissue
– is composed of multilocular adipose cells, which contain
numerous large mitochondria.
– is capable of generating heat by uncoupling oxidative
phosphorylation.
– is found in infants (also in hibernating animals) and is
much reduced in adults.
Loose CT
2. Reticular tissue
– very delicate, forms three-dimensional networks that
support cells
– contains a network of branched reticular fibers in which
macrophages are dispersed.
– invests liver sinusoids and smooth muscle cells and forms
the stroma of bone marrow and lymphatic organs.
3. Elastic tissue
– comprises coarse, branched elastic fibers with a sparse
network of collagen fibers and some fibroblasts filling the
interstitial spaces.
– is present in the dermis, lungs, elastic cartilage, yellow
ligaments of the back (ligamenta flava) and ligaments of
the neck (ligamentum nuchae), as well as in large
(conducting) blood vessels, where it forms fenestrated
sheaths.
B. Dense CT
• contains more fibers but fewer cells than loose CT.
• is adapted to offer resistance and protection.
• is classified by the orientation of its fiber bundles into 2types:
1. Dense irregular CT
– fiber bundles that have no definite orientation.
– constitutes most dense CT.
– is characteristic of the dermis and capsules of many
organs.
2. Dense regular CT
– fiber bundles that arranged in a uniform parallel fashion.
– is present only in
• tendons and
• ligaments
Connective Tissue Cells
• CT cells include many types with different functions.
• Some originate locally and remain in the CT (fixed cells),
whereas others originate elsewhere and remain only
temporarily in CT (transient cells)
• Fixed connective tissue cells include
– Fibroblasts, pericytes, adipose cells ,mast cells,
• Transient connective tissue cells include
– Macrophages, lymphocytes, plasma cells
– Granulocytes
• neutrophils, eosinophils, and basophils.
Connective Tissue Cells
Characteristic CT cell types include both resident cells and
immigrant or wandering cells.
Resident cells are:
• Fibroblasts (secrete the fibers and ground substance of the
ECM).
• Adipocytes (store fat).
• Mast cells (trigger inflammation).
• Macrophages (ingest and remove foreign material or
damaged cells).
Immigrant cells include:
• lymphocytes, monocytes, and Neutrophils, which are all
involved in immune defense and inflammation
CT cells
A. Fibroblasts
– synthesize proteins, such as collagen and elastin, that form
collagen, reticular, and elastic fibers, and the GAGs,
proteoglycans, and glycoproteins of the ECM.
– are also involved in the production of growth factors that
influence cell growth and differentiation.
B. Pericytes
– are smaller than fibroblasts and are located mostly along
capillaries.
C. Adipose cells
- arise from undifferentiated mesenchymal cells.
- are surrounded by a basal lamina.
- are responsible for the synthesis and storage of fat.
1. Uni-Locular adipose cells
- have their cytoplasm and nuclei squeezed into a thin rim
around the periphery to accommodate a single fat droplet.
- have plasmalemma receptors for insulin, growth hormone,
norepinephrine, and glucocorticoids to control the uptake
and release of free Fas and triglycerides.
- generally do not increase in number after a limited postnatal
period.
2. Multi-Locular adipose cells
- contain many small fat droplets.
D. Macrophages & Mononuclear Phagocyte System
- originate in the bone marrow as monocytes.
(monocytes circulate in the bloodstream and migrate into
the CT, where they mature into functional macrophages).
- are generally spherical with a diameter of 10-30 µm.
- are the principle phagocytizing cells of CT responsible for
removing large particulate matter and assisting in the
immune response. (have an important role in removing cell
debris and damaged extracellular components formed during
the physiological involution process).
- secretory cells that produce an impressive array of substances,
including enzymes (eg, collagenase) and cytokines that
participate in defensive and reparative functions, and
they exhibit increased tumor cell–killing capacity.
- also secrete substances that function in wound healing.
- display filopodia, phagocytic vacuoles, lysosomes, and
residual bodies when activated.
- may fuse, when stimulated, to form foreign giant cells.
✹ These multinucleated cells surround and phagocytose large, foreign bodies.
Macrophages are among the most independent cells in the body.
Although they respond to the chemical signals which govern immune responses, individual macrophages
are capable of crawling out of CT, crossing the body's epithelium, and scavenging foreign material on
exposed surfaces such as the alveolar lining of the lung and the conjunctiva of the eye.
●Macrophages, which are distributed throughout the body, are present in most organs and
constitute the mononuclear phagocyte system.
● They are long-living cells and may survive for months in the tissues.
● In certain regions, macrophages have special names, eg, Kupffer cells in the liver,
microglial cells in the CNS, Langerhans cells of the skin, and osteoclasts in bone tissue.
● The process of monocyte-to-macrophage transformation results in an increase in protein
synthesis and cell size. Increases in the Golgi complex and in the number of lysosomes,
microtubules, and microfilaments are also apparent. Macrophages measure between
10 and 30 um and usually have an oval or kidney-shaped nuclei located eccentrically.
Cell Type Location Main Function
Monocyte Blood Precursor of macrophages
Macrophage CT, lymphoid organs, lungs,
bone marrow
Production of cytokines, chemotactic
factors, and several other molecules that
participate in inflammation (defense),
antigen processing and presentation
Kupffer cell Liver Same as macrophages
Microglia cell Nerve tissue of the CNS Same as macrophages
Langerhans cell Skin Antigen processing and presentation
Dendritic cell Lymph nodes Antigen processing and presentation
Osteoclast Bone (fusion of several
macrophages)
Digestion of bone
Multinuclear
giant cell
CT (fusion of several
macrophages)
Segregation and digestion of foreign bodies
Distribution and Main Functions of the Cells of the Mononuclear Phagocyte System.
E. Lymphoid cells
- arise from lymphoid stem cells during hematopoiesis.
- are located throughout the body in the subepithelial CT.
- accumulate in the respiratory system, gastrointestinal tract,
and especially in areas of chronic inflammation.
1. T lymphocytes (T cells) initiate the cell-mediated immune response.
2. B lymphocytes (B cells), following activation by antigen,
differentiate into plasma cells, which function in the humoral
immune response.
3. Null cells lack the surface determinants characteristic of T and B
lymphocytes but many have cytotoxic activity against tumor cells.
F. Plasma cells
- are antibody-manufacturing cells that arise from activated B
lymphocytes.
- are responsible for humoral immunity.
G. Mast cells (molecules produced act locally in paracrine secretion).
- arise from myeloid stem cells during hematopoiesis.
- mediate immediate (type I) hypersensitivity reactions (anaphylactic
reactions) as follows:
1. The first exposure to an allergen leads to production of IgE
antibodies, which bind to receptors on the surface of mast
cells (and basophils), causing them to become sensitized.
Common antigens that may evoke this response include plant
pollens, insect venoms, certain drugs, and foreign serum.
2. During a second exposure to the same allergen, the membrane
bound IgE binds the allergen, triggering degranulation of
mast cells and the release of various mediators.
3. The released mediators include heparin, eosinophil chemotatic
factor (ECF), histamine, and leukotriene C.
a. Histamine increases the permeability of blood vessels.
b. Leukotriene C, also known as slow- reacting
substance of anaphylaxis (SRS-A), includes
slow contraction of smooth muscle.
Mast cell secretion.
(1) IgE molecules are bound to the surface receptors.
(2) After a second exposure to an antigen (eg, bee venom), IgE molecules bound to surface receptors
are cross-linked by the antigen. This activates adenylate cyclase and results in the
phosphorylation of certain proteins.
(3) At the same time, Ca2+ enters the cell.
(4) These events lead to intracellular fusion of specific granules and exocytosis of their contents.
(5) In addition, phospholipases act on membrane phospholipids to produce leukotrienes.
The process of extrusion does not damage the cell, which remains viable and synthesizes
new granules. ECF-A, eosinophil chemotactic factor of anaphylaxis.
H. Granulocytes
- are white blood cells that possess cytoplasmic granules.
- arise from myeloid stem cells during hematopoiesis.
1. Neutrophils
- phagocytose, kill, and digest bacteria at sites of
acute inflammation.
- Pus is an accumulation of dead neutrophils at an
inflammatory site.
2. Eosinophils
- bind to antigen- antibody complexes on the surface
of parasites (e.g., helminthes) and then release
cytotoxins that damage the parasites.
- are attracted by eosinophil chemotatic factor, which
is secreted by mast cells and basophils
3. Basophils
- are similar to mast cells in that they possess FcεRI
receptors; their granules
- house the same primary mediators; and the same
secondary mediators are manufactured de novo from the
phospholipids of their plasmalemma. They differ,
however, in that they circulate via the bloodstream,
Cell Type Representative Product or Activity Representative
Function
Fibroblast,
chondroblast
osteoblast
Production of fibers and ground substance Structural
Plasma cell Production of antibodies Immunological
(defense)
Lymphocyte
(several types)
Production of immunocompetent cells Immunological
(defense)
Eosinophilic leukocyte Participation in allergic and vasoactive
reactions, modulation of mast cell activities and
the inflammatory process
Immunological
(defense)
Neutrophilic leukocyte Phagocytosis of foreign substances, bacteria Defense
Macrophage Secretion of cytokines and other molecules,
phagocytosis of foreign substances and
bacteria, antigen processing and presentation
to other cells
Defense
Mast cell and
basophilic leukocyte
Liberation of pharmacologically active
molecules (eg, histamine)
Defense
(participate in
allergic reactions)
Adipose (fat) cell Storage of neutral fats Energy reservoir,
heat production
Functions of Connective Tissue Cells.

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1. CT ppt for class (1).pptx

  • 2. Connective & Supporting Tissue I. Overview - formed primarily of ECM in which various types of cells are embedded. - functions: •provides structural (mechanical ) support for organs and cells. • serves as a medium for exchange of nutrients and wastes between the blood and tissues ( transport of nutrients and metabolites). • aids in protection against micro organisms and in repair of damage tissues (physical & immunological defense) • provides a site for storage of fat ( reserve energy storage). • heat generation (brown fat), • haemopoiesis (blood cell formation). ☞ BINDING TOGETHER: framework ☞ COMPARTMENTALIZATION
  • 3. • Structurally, connective tissue (CT) is formed by : • cells • fibers • ground substance. • Unlike the other tissues (epithelium, muscle, and nerve), which are formed mainly by cells, • major constituent of CT is extracellular matrix (ECM). • ECM consist of different combinations of protein fibers (collagen, reticular, and elastic) and ground substance. Fibers, predominantly composed of collagen, constitute • tendons, • aponeuroses, • capsules of organs, and • membranes that envelop the CNS (meninges). • They also make up the trabeculae and walls inside several organs, forming the most resistant component of the stroma, or supporting tissue of organs. responsible for the remarkable structural, functional, and pathologic diversity of CT. ➽ Embryologic origin: mesenchyme (mesoderm), except head mesenchyme (neural crest) (unlike most epithelial tissue which is derived from ectoderm and endoderm).
  • 4. II. Extracellular matrix - consists of ground substance, fibers, and tissue fluid. - provides a medium for the transfer of nutrients and waste materials between CT cells and the bloodstream. A. Ground substance (intercellular ) - is a highly hydrated, colorless, transparent, gel-like material that fills the space between the cells and fibers of CT (structural function). (In ordinary CT, it consists mainly of water). - is a complex mixture of • glycosaminoglycans (GAGs), • proteoglycans, and • glycoproteins. - acts as a lubricant and helps prevent the penetration of tissues by foreign particles. Ground substance may be highly modified in the special forms of CT. • In blood, the ground substance lacks stabilizing macromolecules. We call this free-flowing ground substance plasma. • In skeletal tissue, the ground substance may become mineralized by deposition of calcium salts. We call this rigid ground substance bone. • In cartilage, the ground substance is much more solid than in ordinary CT but still retains more resiliency than bone.
  • 5. ●Ground substance is a highly hydrophilic, viscous complex of anionic macromolecules (glycosaminoglycans and proteoglycans) and multiadhesive glycoproteins (laminin, fibronectin, …) that impart strength and rigidity to the matrix by binding to receptor proteins (integrins) on the surface of cells and to the other matrix components. ●the molecules of CT serve other important biological functions, such as serving as a reservoir for hormones controlling cell growth and differentiation. ● The hydrated nature of much CT matrix is also the medium through which nutrients and metabolic wastes are exchanged between cells and their blood supply. ● Ground substance is found in all cavities and clefts between the fibres and cells of CT. ●Water, salts and other low molecular substances are contained within the ground substance, but its main structural constituent are proteoglycans.
  • 6. • Collagen and reticular fibers are formed by the protein collagen • Elastic fibers are composed mainly of the protein elastin. • These fibers are distributed unequally among the types of CT. • Actually, there are two systems of fibers: • collagen system, consisting of collagen and reticular fibers, and • elastic system, consisting of the elastic, elaunin, and oxytalan fibers. • In many cases, the predominant fiber type is responsible for conferring specific properties on the tissue. B. Fibers - are long, slender protein polymers. - include: • collagen fibers • reticular fibers • elastic fibers - are present in different proportions.
  • 7. 1. Collagen fibers – most abundant protein in the human body, representing 30% of its dry weight. – More than 20 types – Produced by fibroblast – are composed of type I collagen, which consists of many closely packed tropocollagen fibrils. – have great tensile strength and impart both flexibility and strength to tissues containing them. – are present in bone, skin, cartilage, tendon, basal lamina, smooth muscle – produced by fibroblasts. – are produced in a two-stage process involving • intracellular events (in fibroblasts) and • extracellular events.
  • 8. 1• Collagens That Form Long Fibrils • The molecules of long fibril–forming collagens aggregate to form fibrils clearly visible in the electron microscope. • These are collagen types I, II, III, V, and XI. • Collagen type I is the most abundant and has a widespread distribution. ►It occurs in tissues as structures that are classically designated as collagen fibers and that form structures such as • bones • dentin • tendons • organ capsules • dermis. 2• Fibril-Associated Collagens • are short structures that bind collagen fibrils to one another and to other components of the ECM. ►They are collagen types IX, XII, and XIV. 3• Collagens That Form Networks (type IV collagen) • The molecules of network-forming collagen, assemble in a meshwork that constitutes the structural component of the basal lamina. 4• Collagens That Form Anchoring Fibrils (type VII collagen) • is present in the anchoring fibrils that bind collagen fibers to the basal lamina. Scars are made of collagen. Types of Collagen
  • 9. Collagen synthesis, an activity originally believed to be restricted to fibroblasts, chondroblasts, osteoblasts, and odontoblasts, has now been shown to be widespread, with many cell types producing this protein. • The principal AAs that make up collagen are glycine (33.5%), proline (12%), and hydroxyproline (10%). • The protein unit that polymerizes to form collagen fibrils is the elongated molecule called tropocollagen. • Tropocollagen consists of three subunit polypeptide chains intertwined in a triple helix. • In collagen types I, II, and III, – tropocollagen molecules aggregate into microfibrillar subunits that are packed together to form fibrils. • Hydrogen bonds and hydrophobic interactions are important in the aggregation and packing of these units. • In a subsequent step, this structure is reinforced by the formation of covalent cross links, a process catalyzed by the activity of the enzyme lysyl oxidase. • In collagen types I and III, these fibrils associate to form fibers. • (In type I, the fibers can associate to form bundles • type II (present in cartilage) occurs as fibrils but does not form fibers or bundles). • Collagen type IV, present in all basement membranes, does not form either fibrils or fibers.
  • 10. Biosynthesis of Collagen Type I 1. Polypeptide achains are assembled on polyribosomes bound to RER membranes and injected into the cisternae as preprocollagen molecules. ●The signal peptide is clipped off, forming procollagen. 2. Hydroxylation of proline and lysine occurs after these AAs are incorporated into polypeptide chains. ● Hydroxylation begins after the peptide chain has reached a certain minimum length and is still bound to the ribosomes. ● enzymes involved are peptidyl proline hydroxylase and peptidyl lysine hydroxylase. 3. Glycosylation of hydroxylysine occurs after its hydroxylation. ● Different collagen types have different amounts of carbohydrate in the form of galactose or glycosylgalactose linked to hydroxylysine. 4. Each chain is synthesized with an extra length of peptides called registration peptides on both the amino-terminal and carboxyl-terminal end. ● extra peptides make the resulting procollagen molecule soluble and prevent its premature intracellular assembly and precipitation as collagen fibrils. ● Procollagen is transported as such out of the cell to the extracellular environment. 5. Outside the cell, procollagen peptidases (protease) remove the registration peptides. ● altered protein (tropocollagen) is able to assemble into polymeric collagen fibrils. ● hydroxyproline residues contribute to the stability of the tropocollagen triple helix, forming hydrogen bonds between its polypeptide chains. 6. Collagen fibrils aggregate spontaneously to form fibers. ● Proteoglycans and structural glycoproteins play an important role in the aggregation of tropocollagen to form fibrils and in the formation of fibers from fibrils. 7. The fibrillar structure is reinforced by the formation of covalent cross-links between tropocollagen molecules. ● This process is catalyzed by the action of the enzyme lysyl oxidase, which also acts in the extracellular space.
  • 11. Collagen synthesis. The assembly of the triple helix and the hydroxylation and glycosylation of procollagen molecules are simultaneous processes that begin as soon as the three chains cross the membrane of the RER. The aggregation of mature collagen molecules (tropocollagen) into fibrils occurs in the extracellular environment. Because collagen synthesis depends on the expression of several genes and on several posttranslation events, many collagen diseases have been described.
  • 12. MEDICAL APPLICATION Collagen synthesis depends on the expression of several genes and several posttranslational events. Pathological conditions are directly attributable to insufficient or abnormal collagen synthesis. Certain mutations in the α1 (I) or α 2 (I) genes lead to osteogenesis imperfecta. ●Many cases of osteogenesis imperfecta : due to deletions of all or part of the α 1 (I) gene. (However, a single AA change is sufficient to cause certain forms of this disease, particularly mutations involving glycine). ● Glycine must be at every third position for the collagen triple helix to form. Other diseases that result from an overaccumulation of collagen. ● progressive systemic sclerosis ● almost all organs present an excessive accumulation of collagen (fibrosis). ● in the skin, digestive tract, muscles, and kidneys, causing hardening and functional impairment of the implicated organs. ● Keloid is a local swelling caused by abnormal amounts of collagen that form in scars of the skin. (Keloids, which occur most often in individuals of black African descent can be a troublesome clinical problem to manage; not only can they be disfiguring, but excision is almost always followed by recurrence). ● Vitamin C (ascorbic acid) deficiency leads to scurvy(degeneration of CT). ● Without this vitamin, fibroblasts synthesize defective collagen, and the defective fibers are not replaced. This process leads to a general degeneration of CT that becomes more pronounced in areas in which collagen renewal takes place at a faster rate The periodontal ligament that holds teeth in their sockets has a relatively high collagen turnover; consequently, this ligament is markedly affected by scurvy, which leads to a loss of teeth. Ascorbic acid is a cofactor for proline hydroxylase(essential for collagen synthesis
  • 13.
  • 14. 2. Reticular fibers (rete, net) - are extremely thin formed of loosely packed tropocollagen fibrils. - are composed primarily of type III collagen - Reticular fibers form thin supporting networks - constitute the architectural framework for - hematopoietic organs (eg, spleen, lymph nodes, red bone marrow) and endocrine glands. - Endoneurium - Found in basement membrane -create a flexible network in organs that are subjected to changes in form or volume, such as the ► arteries ► liver ► uterus ► intestinal muscle layers
  • 15. 3. Elastic fibers - are coiled, branched fibers - are composed of microfibrils of elastin and fibrillin - may be stretched up to 150% of their resting length. - Function - add resilience to CT - Maintain extensible organs(organs that requires ability to expand ) - Distributions - Larynx, Trachea, bronchi, bronchioles, & Inter-alveolar septa - Elastic arteries, Elastic cartilage, vocal ligaments - Skin - ligamenta flava of the vertebral column, ligamenta nuchae of neck
  • 16.
  • 17. MEDICAL APPLICATION Fibrillin is a family of proteins related to the scaffolding necessary for the deposition of elastin. Mutations in the fibrillin gene result in Marfan syndrome, a disease characterized by a lack of resistance in the tissues rich in elastic fibers. Because the large arteries are rich in components of the elastic system and because the blood pressure is high in the aorta, patients with this disease often experience aortic rupture, a life- threatening condition.
  • 18. Glycosaminoglycans (GAGs; originally called acid Muco-polysaccharides) • are linear polysaccharides formed by repeating disaccharide units usually composed of ► uronic acid (glucuronic or iduronic acid) & ► hexosamine (glucosamine or galactosamine ) • With the exception of hyaluronic acid, these linear chains are bound covalently to a protein core, forming a proteoglycan molecule. • Because of the abundance of hydroxyl, carboxyl, and sulfate groups in the carbohydrate moiety of most GAGs, these molecules are intensely hydrophilic and act as poly-anions. • With the exception of hyaluronic acid, all other GAGs
  • 19. ●GAGs attach via core- and link-proteins to a backbone formed by the hyaluronic acid. ● The coiled arrangement of the Hyaluronan and other attached GAGs fills a roughly spherical space with a diameter of ~0.5 µm. This space is called a domain. Neighboring domains overlap and form a more or less continuous 3D molecular sieve in the interstitial spaces of the CTs. ● The large poly-anionic carbohydrates of the GAGs bind large amounts of water and cations. ● The bound water in the domains forms a medium for the diffusion of substances of LMW such as gases, ions and small molecules, which can take the shortest route, for example, from capillaries to CT 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 immobilized 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 depolymerizes hyaluronic acid.
  • 20. Hyaluronan (or hyaluronic acid) is the dominant GAG in CT. . serves as a "backbone" for the assembly of other GAGs in connective and skeletal tissue, which results in even larger molecule complexes ●Hyaluronan is also a major component of the ● synovial fluid (fills joint cavities) ● vitreous body of the eye ● The remaining four major GAGs are Chondroitin sulfate Dermatan sulfate Keratan sulfate Heparan sulfate
  • 21. Schematic diagram of cell-surface syndecan proteoglycan. The core protein spans the plasma membrane through the cytoplasmic domain. The syndecan proteoglycans possess three heparan sulfate chains and sometimes chondroitin sulfate. • The molecular structure of proteoglycans & glycoproteins. A: Proteoglycans contain a core of protein (vertical rod in drawing) to which molecules of 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. In general the three-dimensional structure of proteoglycans can be pictured as a test tube brush, with the wire stem representing the core protein and the bristles representing the sulfated GAGs. Proteoglycans contain a greater amount of carbohydrate than do glycoproteins. core protein GAGs (wire stem) (bristles) B: Glycoproteins are globular protein molecules to which branched chains of monosaccharides are covalently attached. Their polypeptide content is greater than their polysaccharide content.
  • 22. Hypothyroidism – accumulation of excess GAGs (myxedema).
  • 23. Proteoglycans ● are responsible for the highly viscous character of the ground substance. ● 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 GAGs, which form the bulk of the polysaccharides in the ground substance. (Because of these characteristics, proteoglycans can bind to a great number of cations (usually sodium) by electrostatic (ionic) bonds. ● are intensely hydrated structures with a thick layer of solvation water surrounding the molecule. [When fully hydrated, proteoglycans fill a much larger volume than they do in their anhydrous state and are highly viscous]. ●are composed of a core protein associated with the four main GAGs: dermatan sulfate, chondroitin sulfate, keratan sulfate, and heparan sulfate. ● are three-dimensional structures that can be pictured as a test tube brush, with the wire stem representing the protein core and the bristles representing the GAGs.
  • 24. ●are compounds that contain a protein moiety to which carbohydrates are attached. ● In contrast to proteoglycans, the protein moiety usually predominates, and these molecules do not contain the linear polysaccharides formed by repeating disaccharides containing hexosamines. ● Instead, the carbohydrate moiety of glycoproteins is frequently a branched structure. ● Several glycoproteins have been isolated from CT, and they play an important role: interaction between neighboring adult and embryonic cells & adhesion of cells to their substrate. ● Fibronectin (L. fibra, fiber, + nexus, interconnection) is a glycoprotein synthesized by fibroblasts and some epithelial cells and has binding sites for cells, collagen, and GAGs. (Fibronectin is distributed as a network in the intercellular spaces of many tissues). Interactions at these sites help to mediate normal cell adhesion and migration. ● Laminin is a large glycoprotein that participates in adhesion of epithelial cells to the basal lamina, a structure rich in laminin. Glycoproteins (Multiadhesive glycoproteins)
  • 25. B: The structure of laminin, which is formed by three 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. A: The structure of fibronectin. Fibronectin is a dimer bound by S–S groups, formed by serially disposed coiled sites, that bind to type I collagen, heparan sulfate, other proteoglycans, and cell membrane receptors.
  • 27. Types of CT CT Proper loose CT areolar adipose Reticular Elastic Dense CT regular irregular Supporting CT Cartilage hyaline fibrocartila ge Elastic Bone Compact Spongy Fluid CT Blood lymph
  • 28. Connective Tissue Proper A. Loose CT  Also called Areolar Tissue which refers to tissue that contains interstitial space.  possesses fewer cells and fibers  More ground substance than dense CT  Three main types of loose CT 1. Adipose tissue 2. Reticular tissue 3. Elastic tissue
  • 29. Loose CT • 1. Adipose tissue – is the primary site for storage of energy (in the form of triglycerides). – has a rich neurovascular supply. – Insulates organ, acts as cushion – Located throughout the body • 2 types A. White adipose tissue – is composed of unilocular adipose cells. – constitutes almost all the adipose tissue in adults and is found throughout the body. – stores and releases lipids B. Brown adipose tissue – is composed of multilocular adipose cells, which contain numerous large mitochondria. – is capable of generating heat by uncoupling oxidative phosphorylation. – is found in infants (also in hibernating animals) and is much reduced in adults.
  • 30. Loose CT 2. Reticular tissue – very delicate, forms three-dimensional networks that support cells – contains a network of branched reticular fibers in which macrophages are dispersed. – invests liver sinusoids and smooth muscle cells and forms the stroma of bone marrow and lymphatic organs. 3. Elastic tissue – comprises coarse, branched elastic fibers with a sparse network of collagen fibers and some fibroblasts filling the interstitial spaces. – is present in the dermis, lungs, elastic cartilage, yellow ligaments of the back (ligamenta flava) and ligaments of the neck (ligamentum nuchae), as well as in large (conducting) blood vessels, where it forms fenestrated sheaths.
  • 31. B. Dense CT • contains more fibers but fewer cells than loose CT. • is adapted to offer resistance and protection. • is classified by the orientation of its fiber bundles into 2types: 1. Dense irregular CT – fiber bundles that have no definite orientation. – constitutes most dense CT. – is characteristic of the dermis and capsules of many organs. 2. Dense regular CT – fiber bundles that arranged in a uniform parallel fashion. – is present only in • tendons and • ligaments
  • 33. • CT cells include many types with different functions. • Some originate locally and remain in the CT (fixed cells), whereas others originate elsewhere and remain only temporarily in CT (transient cells) • Fixed connective tissue cells include – Fibroblasts, pericytes, adipose cells ,mast cells, • Transient connective tissue cells include – Macrophages, lymphocytes, plasma cells – Granulocytes • neutrophils, eosinophils, and basophils. Connective Tissue Cells
  • 34. Characteristic CT cell types include both resident cells and immigrant or wandering cells. Resident cells are: • Fibroblasts (secrete the fibers and ground substance of the ECM). • Adipocytes (store fat). • Mast cells (trigger inflammation). • Macrophages (ingest and remove foreign material or damaged cells). Immigrant cells include: • lymphocytes, monocytes, and Neutrophils, which are all involved in immune defense and inflammation
  • 35. CT cells A. Fibroblasts – synthesize proteins, such as collagen and elastin, that form collagen, reticular, and elastic fibers, and the GAGs, proteoglycans, and glycoproteins of the ECM. – are also involved in the production of growth factors that influence cell growth and differentiation. B. Pericytes – are smaller than fibroblasts and are located mostly along capillaries.
  • 36. C. Adipose cells - arise from undifferentiated mesenchymal cells. - are surrounded by a basal lamina. - are responsible for the synthesis and storage of fat. 1. Uni-Locular adipose cells - have their cytoplasm and nuclei squeezed into a thin rim around the periphery to accommodate a single fat droplet. - have plasmalemma receptors for insulin, growth hormone, norepinephrine, and glucocorticoids to control the uptake and release of free Fas and triglycerides. - generally do not increase in number after a limited postnatal period. 2. Multi-Locular adipose cells - contain many small fat droplets.
  • 37. D. Macrophages & Mononuclear Phagocyte System - originate in the bone marrow as monocytes. (monocytes circulate in the bloodstream and migrate into the CT, where they mature into functional macrophages). - are generally spherical with a diameter of 10-30 µm. - are the principle phagocytizing cells of CT responsible for removing large particulate matter and assisting in the immune response. (have an important role in removing cell debris and damaged extracellular components formed during the physiological involution process). - secretory cells that produce an impressive array of substances, including enzymes (eg, collagenase) and cytokines that participate in defensive and reparative functions, and they exhibit increased tumor cell–killing capacity. - also secrete substances that function in wound healing. - display filopodia, phagocytic vacuoles, lysosomes, and residual bodies when activated. - may fuse, when stimulated, to form foreign giant cells. ✹ These multinucleated cells surround and phagocytose large, foreign bodies. Macrophages are among the most independent cells in the body. Although they respond to the chemical signals which govern immune responses, individual macrophages are capable of crawling out of CT, crossing the body's epithelium, and scavenging foreign material on exposed surfaces such as the alveolar lining of the lung and the conjunctiva of the eye.
  • 38. ●Macrophages, which are distributed throughout the body, are present in most organs and constitute the mononuclear phagocyte system. ● They are long-living cells and may survive for months in the tissues. ● In certain regions, macrophages have special names, eg, Kupffer cells in the liver, microglial cells in the CNS, Langerhans cells of the skin, and osteoclasts in bone tissue. ● The process of monocyte-to-macrophage transformation results in an increase in protein synthesis and cell size. Increases in the Golgi complex and in the number of lysosomes, microtubules, and microfilaments are also apparent. Macrophages measure between 10 and 30 um and usually have an oval or kidney-shaped nuclei located eccentrically. Cell Type Location Main Function Monocyte Blood Precursor of macrophages Macrophage CT, lymphoid organs, lungs, bone marrow Production of cytokines, chemotactic factors, and several other molecules that participate in inflammation (defense), antigen processing and presentation Kupffer cell Liver Same as macrophages Microglia cell Nerve tissue of the CNS Same as macrophages Langerhans cell Skin Antigen processing and presentation Dendritic cell Lymph nodes Antigen processing and presentation Osteoclast Bone (fusion of several macrophages) Digestion of bone Multinuclear giant cell CT (fusion of several macrophages) Segregation and digestion of foreign bodies Distribution and Main Functions of the Cells of the Mononuclear Phagocyte System.
  • 39. E. Lymphoid cells - arise from lymphoid stem cells during hematopoiesis. - are located throughout the body in the subepithelial CT. - accumulate in the respiratory system, gastrointestinal tract, and especially in areas of chronic inflammation. 1. T lymphocytes (T cells) initiate the cell-mediated immune response. 2. B lymphocytes (B cells), following activation by antigen, differentiate into plasma cells, which function in the humoral immune response. 3. Null cells lack the surface determinants characteristic of T and B lymphocytes but many have cytotoxic activity against tumor cells. F. Plasma cells - are antibody-manufacturing cells that arise from activated B lymphocytes. - are responsible for humoral immunity.
  • 40. G. Mast cells (molecules produced act locally in paracrine secretion). - arise from myeloid stem cells during hematopoiesis. - mediate immediate (type I) hypersensitivity reactions (anaphylactic reactions) as follows: 1. The first exposure to an allergen leads to production of IgE antibodies, which bind to receptors on the surface of mast cells (and basophils), causing them to become sensitized. Common antigens that may evoke this response include plant pollens, insect venoms, certain drugs, and foreign serum. 2. During a second exposure to the same allergen, the membrane bound IgE binds the allergen, triggering degranulation of mast cells and the release of various mediators. 3. The released mediators include heparin, eosinophil chemotatic factor (ECF), histamine, and leukotriene C. a. Histamine increases the permeability of blood vessels. b. Leukotriene C, also known as slow- reacting substance of anaphylaxis (SRS-A), includes slow contraction of smooth muscle.
  • 41. Mast cell secretion. (1) IgE molecules are bound to the surface receptors. (2) After a second exposure to an antigen (eg, bee venom), IgE molecules bound to surface receptors are cross-linked by the antigen. This activates adenylate cyclase and results in the phosphorylation of certain proteins. (3) At the same time, Ca2+ enters the cell. (4) These events lead to intracellular fusion of specific granules and exocytosis of their contents. (5) In addition, phospholipases act on membrane phospholipids to produce leukotrienes. The process of extrusion does not damage the cell, which remains viable and synthesizes new granules. ECF-A, eosinophil chemotactic factor of anaphylaxis.
  • 42. H. Granulocytes - are white blood cells that possess cytoplasmic granules. - arise from myeloid stem cells during hematopoiesis. 1. Neutrophils - phagocytose, kill, and digest bacteria at sites of acute inflammation. - Pus is an accumulation of dead neutrophils at an inflammatory site. 2. Eosinophils - bind to antigen- antibody complexes on the surface of parasites (e.g., helminthes) and then release cytotoxins that damage the parasites. - are attracted by eosinophil chemotatic factor, which is secreted by mast cells and basophils 3. Basophils - are similar to mast cells in that they possess FcεRI receptors; their granules - house the same primary mediators; and the same secondary mediators are manufactured de novo from the phospholipids of their plasmalemma. They differ, however, in that they circulate via the bloodstream,
  • 43. Cell Type Representative Product or Activity Representative Function Fibroblast, chondroblast osteoblast Production of fibers and ground substance Structural Plasma cell Production of antibodies Immunological (defense) Lymphocyte (several types) Production of immunocompetent cells Immunological (defense) Eosinophilic leukocyte Participation in allergic and vasoactive reactions, modulation of mast cell activities and the inflammatory process Immunological (defense) Neutrophilic leukocyte Phagocytosis of foreign substances, bacteria Defense Macrophage Secretion of cytokines and other molecules, phagocytosis of foreign substances and bacteria, antigen processing and presentation to other cells Defense Mast cell and basophilic leukocyte Liberation of pharmacologically active molecules (eg, histamine) Defense (participate in allergic reactions) Adipose (fat) cell Storage of neutral fats Energy reservoir, heat production Functions of Connective Tissue Cells.