Connective Tissue Flashcards
Connective tissue is formed by three classes of
components:
- Cells
- Fibers
- Ground substance.
The major constituent of connective tissue is
Extracellular matrix
Extracellular matrices consist of
different combinations of
- Protein fibers (collagen, reticular, and elastic fibers)
- Ground substance.
Ground substance is a complex of
- Anionic hydrophilic proteoglycans
- Glycosaminoglycans
- Mmultiadhesive glycoproteins (laminin, fibronectin, and others)
Ground substance stabilizes the ECM by
binding to receptor proteins (integrins) on the surface of
cells and to the other matrix components.
The connective tissues originate from
the mesenchyme, an embryonic tissue formed by elongated undifferentiated cells, the mesenchymal cells
Mesenchymal cells are characterized by:
oval nuclei with prominent nucleoli and fine chromatin. They possess many thin cytoplasmic processes and are immersed in an abundant and viscous extracellular substance containing few fibers
The mesenchyme develops mainly from
the middle layer
of the embryo, the mesoderm
Mesenchyme also develops into
other types of structures, such as:
- Blood cells
- Endothelial cells,
- Muscle cells.
Most common cells in connective tissue:
Fibroblast
Fibroblasts synthesize most components of connective tissue ECM, including:
- Proteins, such as collagen and elastin, which upon secretion form collagen, reticular, and elastic fibers
- Glycosaminoglycans
- Proteoglycans
- Glycoproteins
Fibroblast denotes
The active cell
Fibrocyte denotes
The quiescent cell.
Myofibroblast are responsible for
A process called wound contraction.
In the electron microscope, macrophages are characterized by
an irregular surface with pleats, protrusions, and indentations.
(A morphologic expression of their active pinocytotic andphagocytic activities.)
Macrophages functions
- Phagocytose cell debris, abnormal extracellular matrix elements, neoplastic cells, bacteria, and inert elements that penetrate the organism.
- They are antigen presenting cells that participate in the processes of partialdigestion and presentation of antigen to other cells .
- Participate in cell-mediated resistance to infection by bacteria, viruses, protozoans, fungi, and metazoans (eg, parasitic worms); in cell-mediated resistance to tumors
- Extrahepatic bile production
- Iron metabolism
- Fat metabolism
- Destruction of aged erythrocytes.
When macrophages are stimulated
they change their morphological characteristics and metabolism. They become activated macrophages
Mast cells have cytoplasm that is filled with
basophilic secretory
granules.
Mast cells are
(size)
7–30 um
Because of their high content of acidic radicals in their sulfated glycosaminoglycans, mast cell granules display
Metachromasia
Mast cell granules contain and release from granules:
- Heparin, a sulfated glycosaminoglycan 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 leukocytes and other cells of the immune system.
- Phospholipid precursers for conversion to prostoglandins, leukotrienes and other important lipid mediators of the inflammatory process.
Mast cells occur in many connective tissues, but are especially numerous near
- Small blood vessels in -skin & mesenteries (perivascularmast cells)
- Mucosa lining digestive and respiratory tracts (mucosal mast cells).
Release of the chemical mediators stored in mast cells promotes the allergic reactions known as
immediate hypersensitivity reactions
Mast cell antibody
IgE
Leukocytes leave blood by migrating between the
endothelial cells lining capillaries and postcapillary venules to enter connective tissue by a process called
Diapedesis
The three main types of connective tissue fibers are:
- Collagen
- Reticular
- Elastic fibers.
Reticular fibers contain type (collagen)
III collagen
Deficiency of collagen type III found in
Ehlers–Danlos type IV disease
Ehlers–Danlos type IV disease is characterized by
ruptures in arteries and the intestine, both
structures rich in reticular fibers.
Reticular fibers constitute a network around
the parenchymal cells of various organs (eg, liver, endocrine glands) and are particularly abundant in the framework of hematopoietic organs (eg, spleen, lymph nodes, red bone marrow).
Ehlers-Danlos type VI
Faulty lysine hydroxylation Augmented skin elasticity, rupture of eyeball
Ehlers-Danlos type VII
Decrease in procollagen peptidase activity
Increased articular mobility, frequent luxation
Scurvy Lack of vitamin C
- Ulceration of gums
- Hemorrhages
(cofactor for prolyl hydroxylase)
Osteogenesis imperfecta
Change of one nucleotide in genes for collagen
type I Spontaneous fractures, cardiac insufficiency
Elastic fibers are also thinner than
Type I collagen fiber
Elastic fibers are a composite of
Fibrillin microfibrils embedded in a larger mass of cross linked elastin
Formation of elastic fibers.
- Microfibrils( 10 nm) composed of the glycoprotein fibrillin (350 kDa) is secreted by fibroblasts, smooth muscle cells or other cells.
- Elastin is deposited
- Elastin accumulates and ultimately occupies the center of an elastic fiber,
which retains fibrillin microfibrils at the surface
Microfibrils of fibrillin alone are used in some organs, such as
to hold in
place the lens of the eye.
Such microfibrils are not elastic but are highly
resistant to pulling forces, whereas the mature elastic fibers stretch
easily in response to tension.
Elastin molecules are
(Shape)
globular
Elastin molecules are
(size)
molecular mass 70 kDa
Elastin molecules are secreted by
fibro-blasts in connective
tissue and by smooth muscle cells in the walls of blood vessels
Elastin molecules are rich in
(Amino acids)
glycine and proline
Elastin contains two unusual amino acids:
Desmosine and Isodesmosine
which are
produced when covalent cross-links are formed among four lysinere sidues in different elastin molecules
Elastin is resistant to digestion by
most
proteases, but is easily hydrolyzed by pancreatic elastase.
Marfan syndrome is caused by
mutations in the FBN1 gene on chromosome 15 which encodes the glycoprotein fibrillin-1, a component of the extracellular matrix. Fibrillin-1 protein is essential for the proper formation of the extracellular matrix, including the biogenesis and maintenance of elastic fibers.
Ground Substance of ECM made from 3 substance:
- GAG’s
- Proteoglycans
- Multiadhesive glycoproteins
GAGs (originally called mucopolysaccharides) are
- linear polysaccharides formed by repeating disaccharide units usually composed of a uronic acid and a hexosamine.
- The hexosamine can be glucosamine or galactosamine
- The uronic acid can be glucuronic or iduronic acid.
The largest, most unique, and most
ubiquitous GAG is
hyaluronic acid
Hyaluronic acid is a long polymer of
the
disaccharide glucosamine – glucuronate
hyaluronic acid molecular
weight
100s to 1000s kDa
Hyaluronic acid is synthesized directly into
the ECM by
an enzyme complex, hyaluronate synthase, located in the
cell membrane of many cells.
All other GAGs are
- Much smaller (10–40 kDa)
- Covalently attached to proteins (as parts of proteoglycans)
- Synthesized in Golgi complexes,
- Rich in sulfate.
The four main GAGs found in proteoglycans are
- Dermatan sulfate
- Chondroitin sulfates
- Keratan sulfate
- Heparan sulfate
All of which have different disaccharide units and tissue distributions
Proteoglycans are composed of
a core protein to which are covalently
attached various numbers and combinations of the sulfated GAGs
The dominant proteoglycan in cartilage.
aggrecan
In aggrecan the core protein has
several chondroitin sulfate and keratan sulfate chains and is in turn bound via a link protein to hyaluronic acid.
In cartilage, the core proteins of secreted proteoglycans are bound via small link proteins to
a hyaluronic acid chain forming much larger structures—proteoglycan aggregates.
Cell-surface proteoglycans such as syndecan are present on many types
of cells, particularly
epithelial cells
The core protein of cell-surface
proteoglycans spans
the plasma membrane, with a short cytoplasmic
extension.
|Deficiency in lysosomal enzymes
causes glycosaminoglycan degradation to be blocked.
Disorders in humans, including
- Hurler
- Hunter
- Sanfilippo
- Morquio syndromes.
Bacteria that produce
hyaluronidase, an enzyme that hydrolyzes hyaluronic acid and other glycosaminoglycans, have
greater invasive power
Multiadhesive glycoproteins have carbohydrates attached, but in contrast to proteoglycans
the protein moiety usually predominates.
The carbohydrate moiety of glycoproteins is frequently
a branched structure.
Multiadhesive glycoproteins are
- Fibronectin
- laminin
About laminin …
trimeric, cross-shaped glycoprotein that participates in the adhesion of epithelial cells to the basal lamina, with binding sites for type IVcollagen, GAGs, and integrins.
About Fibronectin
dimeric molecule, with a molecular mass of 222–240 kDa, has
binding sites for collagens, certain GAGs, and integrins of cell
membranes, ie, it is multiadhesive.
Glycoproteins have important roles in
the adhesion of cells to their substrate.
Cells interact with extracellular matrix components by using cell-surface molecules called
integrins,
Integrins bind their ligands in the ECM
with relatively low affinity, allowing cells to explore their environment
without losing attachment to it or becoming glued to it.
Integrins also interact with the cytoskeleton, usually
The actin microfilaments
Integrins also interact with the cytoskeleton, usually the actin microfilaments, an interaction mediated by several intracellular proteins, such as
talin and vinculin.
Intergrin molecule streucture
Heterodimer, with
alpha and beta chains. The head portion may protrude some 20 nm from the surface of the
cell membrane into the ECM where it interacts with fibronectin, laminin, or
collagens.
There are two general classes of connective tissue proper:
loose and dense
Loose connective tissue is a very common type of connective tissue that supports many structures which are
normally under some pressure
and low friction.
Loose connective tissue.It usually .
- supports epithelial tissue
- Forms a layer around small blood and lymphatic vessels
- Fills the spaces between muscle and nerve fibers.
- Is found in the papillary layer of the dermis
- Is found in the hypodermis
- Is found in the linings of the peritoneal and pleural cavities,
- Is found in glands
- Is found in the mucous membranes
Loose connective tissue, sometimes called
areolar tissue
The most numerous cells of loose connective tissue are
fibroblasts and macrophages,
Dense connective tissue is adapted to
offer resistance and protection.
Dense connective tissue is …………………. than is loose connective tissue.
less flexible and far more
resistant to stress
Dense connective tissue is known as dense irregular connective tissue when
the collagen fibers are arranged in
bundles without a definite orientation.
Reticular fibers of type III collagen are produced by specialized fibroblasts called
reticular cells
Heavily glycosylated reticular fibers provide the architectural framework that creates special
microenvironments for
hematopoietic organs and lymphoid organs
(bone marrow, lymph nodes, and spleen).
Mucous tissue is found mainly
in the umbilical cord and fetal tissues.
Mucous tissue has an abundance of ground substance
composed chiefly of
hyaluronic acid, making it a jellylike tissue
containing very few collagen fibers with scattered fibroblasts
Mucous tissue is the principal component of the umbilical cord,
where it is referred to as
Wharton’s jelly.
