Flashcards in Connective Tissue And Components Deck (97):
what are the structural function of ECM?
maintains the three-dimensional structure of the body, forms the sheet of the basement membrane (basal lamina), and holds cells and tissues together
What are the regulatory functions of the ECM?
Regulates processes like proliferation, differentiation, migration, and cell-cell recognition. It can prevent of limit the movement of cancer cells and microorganisms...
MMP-group of enzymes that constantly remodel the ECM, includes the collagenases
What does the dysregulation of MMPs lead to?
The spread of cancer-due to the fact that the ECM can limit cancer cells from moving, so if it's not being maintained then the cells could move
What are the insoluble proteins of the extracellular matrix?
Collagen and elastin
Most abundant fibrous protein (25-30% of total body protein mass).
What is the structure of a typical collagen molecule?
A triple helix of three alpha chains which are tightly wound around each other and form a rope like structure
Glycine in Collagen
Glycine is found in each third position of the alpha chain, which allows a tight-winding of the triple helix.
Proline in Collagen
Abundant and lead to "kinks" (due to their ring structure) in the protein chain that allow for tight winding
Hydroxyproline and Collagen
Hydroxyproline residues stabilize the triple helix via MANY hydrogen bonds between the alpha chains
Lysine and collagen
Form covalent bonds and cross-link tropocollagen
Hydroxylysine residues allow for the additions of sugars
What are the 3 general types of collagen fibers?
Fibril forming, network forming, and fibril associated.
Collagen Type 1
Most common type. Fibril Forming. Makes up the skin, bone, tendon, blood vessels, and cornea
Cartilage, intervertebral disk, and vitreous body. Fibril forming.
Collagen Type III
Fibril forming. Makes up blood vessels and fetal skin
Collagen Type IV
Network forming. Makes up the basement membrane.
Collagen Type VII
Network Forming. Found beneath stratified squamous epithelia.
Collagen Type IX
Fibril Associated. Found in cartilage
Collagen Type XII
Fibril Associated. Found in tissue, ligaments, and some other issues.
Collagen in the bones
Arranged to resist mechanical shear
Collagen in tendons
Bundles in tight, parallel fibers and provides great strength
Collagen is created at the level of a soluble procollagen (still has pro-peptides)
The 3 pro-alpha-chains are modified by specific hydroxylation or glycosylation and a triple helix is formed.
Molecule is released into the ECM and the propeptides are cleaved forming an insoluble collagen.
Collagen molecules associate to form a collagen fibril.
Extracellular cross linking with lysine or modified lysine results in mature collagen fibers.
Where is procollagen synthesized?
Fibroblasts, osteoblasts, and chondroblasts
What do COL1A1 and COL1A2 lead to?
Two a1 chains and one a2 chain for the triple helix.
What is the cofactor for prolyl hydroxylase and lysyl hydroxylase?
Vitamin C (ascorbic acid)
A hydroxylated proline molecule that allows hydrogen bonds between the three alpha chains (stabilizes the triple helix)
Hydroxylated lysine that can be further glycosylated by glucose or galactose
What are the three functions of propeptides?
1) needed in cytosol for the linkage of the correct three pro-alpha-chains to each other by disulfide bonds
2) Allow efficient winding during triple helix formation
3) Keep the procollagen soluble
Enzymes that cleave the propeptides from the procollagen.
Collagen after the propeptides have been cleaved. Tropocollagen molecules spontaneously associate to form a collagen fibril (each overlaps its neighbor) leading to a striated appearance.
What does scurvy cause?
Decreased stability and tensile strength of collagen, which leads to bleeding gums, hemorrhages, and poor wound healing.
Is is extracellular cross-linking performed?
The EC enzyme lysyl oxidase (require copper) oxidatively deaminates lysine residues in collagen. This results in a free ammonia and an aldehyde residue known as allysine (or hydroxyallysine). The reactive aldehyde forms a covalent bond with other lysine or modified lysine residues.
What happens if there is a copper deficiency?
reduced collagen cross-linking
What can cause Ehlers-Danlos Syndrome?
Connective tissue disorder. Can result from a mutation of a gene for the pro-alpha chains of collagen or result from a hereditary defect related to one of the enzymes that are needed for correct collagen synthesis/
What types of collagen are usually affected by Ehlers-Danlos Syndrome?
Type I, III, and V
What are the symptoms of classic (Type V) Ehlers-Danlos syndrome?
Hypermobility of joints and hyperextensibility of the skin
Vascular Ehlers-Danlos Sndrome
Caused by defects of type III collagen and leads to fragility of skin and vascular walls. It is most serious as arteries can rupture.
Due to defective collagen synthesis either by less than normal collagen or abnormal collagen of type 1 (displacement of glycine) resulting in bone fractures and bending.
OI Type 1
Mildest form leads to early childhood long bone fractures after minor trauma (goes away in adulthood). Blue sclera due to it being thin and revealing the appearance of the uveal tissue (pigmented layer)
OI Type II
Most severe form . OI congenita. Leads to death in utero or neonatal due to respiratory problems. Small rib cage and underdeveloped lungs.
OI Type III
OI Type IV
Deforming with normal sclerae
Highly cross-linked insoluble structure. It is the major protein in elastic fibers which allow the flexibility in blood vessels, lungs, and ligament, and skin.
Tropoelastin is secreted from fibroblasts into the ECM as a highly soluble liner at polypeptide (about 700 amino acids). The protein fibrillin-1 acts as a scaffold for the EC tropoelastin which needs to be cross linked in order to become insulble. Lysyl oxidase forms extracellular allysine residues which are needed for cross linking. The aldehydes form covalent binds with other lysine or allysine residues of elastin.
Desmosine and Isodesmosine
Characteristic for elastic and allow it to stretch and bend in any direction.
What is linked to form desmosine?
3 allysine and 1 lysine
Force that allows the stretched structure of elastin to reform to its original form.
Found in elastin. Sequence that is rich in lysine (charged) and alanine (uncharged). Contributes to the hydrophobic effect
Found in elastin. Rich in glycine, valine, and proline. Contributes to the hydrophobic effect.
Autosomal dominant defect in the gene that encoded fibrillin-1 (connective tissue disorder)
What are the three major components of connective tissue?
Cells, fibers, and ground substance
What are the main functions of connective tissues?
Support, repair, defense (immune system), nutrition
What are the permanent residents of connective tissue?
Fibroblasts, adipose cells, macrophages/monocytes, mast cells, mesenchymal stem cells.
What is the transient cell population?
Lymphocytes, plasma cells, eosinophils, basophils, and neutrophils
Most common cell in connective tissue, synthesize fibers and ground substance, spindle shaped, may be active (fibroblasts) or inactive (fibrocytes)
Involved in wound healing, has contractile filaments. Less ordered appearance in EM.
Fibroblasts in embryo
Cells are plump and separated by early collagen
Large oval nucleus, spindle shaped basophilic cytoplasm, active protein synthesis
Collagen synthesis stops, loose basophilic cytoplasm, nucleus shrinks. Flat nuclei.
Found in CT. Store energy and have good blood supply.
One large fat droplet. Have a signet ring appearance, with nucleus pushed to periphery of the cell. Large fat vacuole. Major energy source (TAGs)
Brown fat. Many lipid droplets. Central nucleus. Rich in mitochondria. Highly vascular. Mainly functions in heat production. specialized locations in the body and neck of neonates.
Moved in marrow and moved to tissue. Derived from monocytes. they have an irregular cell membrane with cytoplasmic extensions. they are phagocytic (produce cytokines)..
Electron Micrograph Features of Macrophages
RER, prominent Golgi, lots of lysosomes, and irregular nucleus outline
Originate in bone marrow from precursor cells lacking cytoplasmic granules. Gain cytoplasmic granules when they migrate to CT.
Vasoactive products of mast cells. They are released from the cell membrane of the mast cells as metabolites of arachnidonic acid
Mast Cell Granules
Contain histamine, heparin, chemotactic activators that attract monocytes, neutrophils, and eosinophils to site of mast cell activation
Coloring observed in mast cells due to a change in structure of the dye after binding.
Small, spherical (little cytoplasm), condensed basophilic nucleus, immune cells (B and T cells), B-lymphocytes develop into plasma cells
Synthesizes and secretes single class of immunoglobulin (glycoprotein). Basophilic cytoplasm with a soccer ball, "clock face" distribution of chromatin.
Granules in the cytoplasm. Condensed, bilobed nucleus. Helps with phagocytosis of antibody-antigen complexes and kills parasitic worms.
Type V Collagen
Amnion and chorion in the fetus, makes up muscle and tendon sheaths. Doesn't form banded fibrils.
Type III collagen (primarily). Short, thin, and branching. Found I organs with large volume changes (blood vessels, arteries, spleen, testes). Silver staying and PAS positive. First type of collagen synthesized during wound healing.
What are the three developmental stages of elastic fibers?
What makes up elastin?
Glycine, proline, desmosine, and isodesmosine
what are the two components of elastic fibers?
Fibrillin and elastin
What are the core proteins that make up proteoglycans?
Aggrecan, decorin, versican, and syndecan
which glycoprotein can be commonly found in the basement membrane?
What stain do you use for glycoproteins and proteoglycans?
Periodic Acid Schiff
Mucous Connective Tissue
Few cells or fibers, mainly ground substance (jelly-like). Umbilical cord or vitreous humor in eye
Embryonic connective tissue
Loose Areolar CT
Fills the space between other tissues (large number of cells), flexible and rich in blood supply, not resistant to stress
Dense Irregular CT
Fewer cells, more cells than Areolar tissue. there is no orientation of collagen fibers, which means there is resistance to stress in all directions. Makes up organs, periosteum, dermis
Dense Regular Connective Tissue
Specific orientation of collagen fibers. Makes up tendons and ligaments. Imparts tensile strength.
Innermost layer. CT covering each cell. Dense regular CT
CT covers a group of cells. Dense regular CT.
CT covers the entire tendon (outermost layer). Dense regular CT
Shorter than elastic fibers, branched, and thin
Made of elastic fibers (yellow colored). Found in the arteries, penis, vocal cords.
Scar is raised more than normal, but within the normal boundary
Scar exceeds boundary, extending into surrounding tissue. Commonly seen in people of African descent.