lesson 6 gritti Flashcards
what is the major constituent of connective tissue?
the ECM
different connective tissues in the body differ in composition/amount of ground substance, cells and fibers (constituents of the ECM)
what is the origin of the connective tissue?
embryonic mesenchyme
(a type of loosely organized, undifferentiated tissue derived primarily from the mesoderm during embryogenesis).
what’s the name of the mesenchymal cells that remain in the adult connective tissue and what’s their main function?
mesenchymal stroma cells
they are multipotent and fundamental for tissue homeostasis and regenerative medicine
inborn cells
cells born in the tissue that exert their function in the tissue
migrated cells
cells that come from the circulation (hematopoietic origin) and migrate in the tissue only to exert their function
ground substance components
viscous gel
water plus:
-proteoglycans
-glycosaminoglycans
-multiadhesive glycoproteins (fibronectin and laminin for example)
macrophages
have an hematopoietic origin or an embryo origin
very long-lived in tissues and exert important functions (removal of dead cells or turnover of protein fibers)
their names vary depending on which tissue their in
-have a very important role in inflammation and repair after tissue damage
-can present antigens
–>involved in innate immunity
connective tissue classification is based on?
the composition of the ECM
EMT
-waves of EMT are fundamental for the developing of multicellular organisms
-the mesoderm is formed as a consequence of EMT
-can be deregulated: if epithelial cells start to become mesenchymal cells they invade the connective tissue, go in the circulation–>crucial process in pathology
fibroblasts
-key cell type in connective tissue
-can be active (bigger size) or quiescent (smaller size)
-produce and secrete most of the ECM (including the protein fibers- collagen, elastin or fibronectin- and the ground substance)
-in adult life they are quiescent for the most part and do not undergo proliferation
-their active state in adult life can be stimulated by grow factors, such as the fibroblast grow factor
-in adult life they rarely undergo mitotic division but it can be stimulated thanks to locally released grow factors (for example when a part of the tissue has been damaged and we need new fibroblasts for the repair)
-are enriched in actin and so they have a well developed contractile function
myofibroblasts
important for the inflammatory response to injury
specialized connective tissues include:
bone, blood, tendons, ligaments, adipose tissue, cartilage
adipocytes
cells often present in the connective tissue of most organs
large and mesenchymal derived cells–>responsible for triglyceride storage or production of heat.
white fat cells
present singly or in small groups in loose connective tissue with the function of triglyceride storage
brown fat cells
responsible for thermoregulation, abundant in newborns
connective tissue with a lot of adipocytes is called
adipose connective tissue
mast cells
-often located near small blood vessels
-contain basophilic secretory granules
-these cells develop in the bone marrow and differentiate completely in the connective tissue
-involved in the inflammatory and immune response–>basophilic granules secrete histamine, heparin and other inflammatory mediators
leukocytes–>transient cells
-circulate into the blood stream and invade the connective tissue as a consequence of an immune response
-short lived
plasma cells
-lifespan of 10-20 days
-secrete antibodies that mediate immunity
-characterized by round nuclei with peripherally dispersed heterochromatin, large Golgi apparati, large ER
-ER synthesizes the antibodies and the Golgi apparatus is involved in the terminal glycosylation of antibodies
pericytes
-wrapped around blood vessels and strengthen the wall of the vessels
-heterogeneous origins
-important component of the blood brain barrier: pericytes are insulator of blood vessels in the central nervous system (prevents the entering of unwanted substances in the central nervous system)
-has been proved that they work as stem cells and that they are part of the mesenchymal stroma cells that are retained in the connective tissue in post natal and adult life
protein fibers of the extracellular matrix
collagen->mostly type I, give tensile strength
elastic fibers->made of elastin and fibrillin, give elasticity
reticular fibers->composed of type III collagen, give support
collagen
-most abundant protein in mammals
-each collagen molecule is formed by 3 alpha chains wrapped around in a triple helix
multiple collagen molecules aggregate to form fibrils
multiple fibrils aggregate to form fibers
-collagen is rich of glycine and hydroxiproline
-secreted by fibroblasts or the other cells of the connective tissue (chondroblasts, osteoblasts)
which type of collagen is present in the basal lamina?
collagen type 4
which type of collagen is present in the lamina reticularis?
collagen type 3 (reticular fibers are made of collagen type 3)
name of the enzymes that degrade collagen for collagen turnover to happen
collagenases
what happens if you don’t have vitamin c?
no hydroxylation of proline->collagen fibers less stable->bone fragility, increase mobility, laxation
the formation of elastic fibers is due to 2 main events
-microfibril formation
-elastogenesis
elastin is rich (in terms of amino acids) of:
proline and glycine
elastin is hydrolyzed by?
pancreatic elastase
what allows the crosslinking of elastin during elastic fiber formation?
thanks to the cross linking the elastic fibers can stretch till a certain point (to avoid over-stretching) and then can reacquire their original conformation.
what’s the cause of Marfan syndrome?
mutation in fibrillin 1
one of the main consequences is the weakness of blood vessels.
components of ground substance, what’s its main function?
GAGs
multiadhesive glycoproteins
proteoglycans
thanks to them the connective tissue layer is generally permeable to solutes and proteins
NB: the degree of permeability varies depending on the connective tissue
-it acts as a lubricant and as a protective barrier
-occupies the space between fibrillar and cellular elements of the connective tissue
proteoglycans structure
protein core+ glycosaminoglycans
-synthetised in the ER, mature in the Golgi (where the GAGs side chains are added) and are secreted from the cell by exocytosis
GAGs
-give viscosity and charge to the ground substance
-repeating disaccharide units, usually an hexosamine (that can be glucosamine or galactosamine) and a uronic acid (can be glucoronate or iduronate)
multiadhesive glycoproteins, main function
stabilize the ECM and link it to the cell surface
hyaluronic acid
-largest GAG
-made of glucosamine and glucoronate
-synthetised directly in the ECM by hyaluronan synthase
-very long polymer
proteoglycan aggregate made of:
proteoglycans and a core of hyaluronic acid–>brush like structure
4 major GAGs in proteoglycans
keratan sulfate
heparan sulfate
dermatan sulfate
chondroitin sulfate
name of the enzyme that helps the addition of the GAGs to the protein core for the formation of the proteoglycan.
what’s the name of the enzyme for the degradation of proteoglycans?
-sugar transferases, it happens in golgi
-hydrolases
multiadhesive glycoproteins
-LINKING PROTEINS: allow the cell to bind to its ECM
-they bind on one side transmembrane proteins and on the other side hyaluronic acid, collagen fibers etc
-have an important role in maintaining the tissue structure
examples of multiadhesive glycoproteins
laminin
tenascin
osteopontin
fibronectin
Wharton’s jelly
-gelatinous substance only present in the umbilical cord to protect blood vessels
-made of GAGs: hyaluronic acid and chondroitin sulfate
loose connective tissue or areolar tissue
-more cells than collagen fibers
-loose arrangement of fibers (collagen and elastic)
-present just below the epithelium
-can be found in association to glands, blood vessels and internal organs
-site of inflammatory and immune reactions
-present various cells types other than fibroblasts
-allows diffusion of oxygen and nutrients
dense regular connective tissue
-fewer cells, more fibers
-densely packed fibers arranged in parallel with fibroblasts parallel to the fibers
-can be collagenous (thick collagen fibers, mainly type I) or elastic (thinner elastic fibers
-found in ligaments or tendons, allowing resistance to axial loads
-no empty spaces can be found
dense irregular connective tissue
-few cells positioned in between dense irregularly organized collagen (and some elastic) fibers
-little ground substance
-found in joint capsules, in the muscle fascia etc
-gives strength
-you can see empty spaces
