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Flashcards in Connective Tissue And Components Deck (97):
1

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

2

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...

3

Matrix Metallo-proteinases

MMP-group of enzymes that constantly remodel the ECM, includes the collagenases

4

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

5

What are the insoluble proteins of the extracellular matrix?

Collagen and elastin

6

Collagen

Most abundant fibrous protein (25-30% of total body protein mass).

7

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

8

Glycine in Collagen

Glycine is found in each third position of the alpha chain, which allows a tight-winding of the triple helix.

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Proline in Collagen

Abundant and lead to "kinks" (due to their ring structure) in the protein chain that allow for tight winding

10

Hydroxyproline and Collagen

Hydroxyproline residues stabilize the triple helix via MANY hydrogen bonds between the alpha chains

11

Lysine and collagen

Form covalent bonds and cross-link tropocollagen

12

Hydroxylysine

Hydroxylysine residues allow for the additions of sugars

13

What are the 3 general types of collagen fibers?

Fibril forming, network forming, and fibril associated.

14

Collagen Type 1

Most common type. Fibril Forming. Makes up the skin, bone, tendon, blood vessels, and cornea

15

Collagen Type2

Cartilage, intervertebral disk, and vitreous body. Fibril forming.

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Collagen Type III

Fibril forming. Makes up blood vessels and fetal skin

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Collagen Type IV

Network forming. Makes up the basement membrane.

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Collagen Type VII

Network Forming. Found beneath stratified squamous epithelia.

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Collagen Type IX

Fibril Associated. Found in cartilage

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Collagen Type XII

Fibril Associated. Found in tissue, ligaments, and some other issues.

21

Collagen in the bones

Arranged to resist mechanical shear

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Collagen in tendons

Bundles in tight, parallel fibers and provides great strength

23

Collagen Biosynthesis

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.

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Where is procollagen synthesized?

Fibroblasts, osteoblasts, and chondroblasts

25

What do COL1A1 and COL1A2 lead to?

Two a1 chains and one a2 chain for the triple helix.

26

What is the cofactor for prolyl hydroxylase and lysyl hydroxylase?

Vitamin C (ascorbic acid)

27

Hydroxyproline

A hydroxylated proline molecule that allows hydrogen bonds between the three alpha chains (stabilizes the triple helix)

28

Hydroxylysine

Hydroxylated lysine that can be further glycosylated by glucose or galactose

29

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

30

Procollagen Peptidases

Enzymes that cleave the propeptides from the procollagen.

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Tropocollagen

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.

32

What does scurvy cause?

Decreased stability and tensile strength of collagen, which leads to bleeding gums, hemorrhages, and poor wound healing.

33

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.

34

What happens if there is a copper deficiency?

reduced collagen cross-linking

35

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/

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What types of collagen are usually affected by Ehlers-Danlos Syndrome?

Type I, III, and V

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What are the symptoms of classic (Type V) Ehlers-Danlos syndrome?

Hypermobility of joints and hyperextensibility of the skin

38

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.

39

Osteogenesis Impefecta

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.

40

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)

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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.

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OI Type III

Severe

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OI Type IV

Deforming with normal sclerae

44

Elastin

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.

45

Elastin Synthesis

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.

46

Desmosine and Isodesmosine

Characteristic for elastic and allow it to stretch and bend in any direction.

47

What is linked to form desmosine?

3 allysine and 1 lysine

48

Hydrophobic Affect

Force that allows the stretched structure of elastin to reform to its original form.

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Hydrophilic Sequence

Found in elastin. Sequence that is rich in lysine (charged) and alanine (uncharged). Contributes to the hydrophobic effect

50

Hydrophobic Sequence

Found in elastin. Rich in glycine, valine, and proline. Contributes to the hydrophobic effect.

51

Marfan Syndrome

Autosomal dominant defect in the gene that encoded fibrillin-1 (connective tissue disorder)

52

What are the three major components of connective tissue?

Cells, fibers, and ground substance

53

What are the main functions of connective tissues?

Support, repair, defense (immune system), nutrition

54

What are the permanent residents of connective tissue?

Fibroblasts, adipose cells, macrophages/monocytes, mast cells, mesenchymal stem cells.

55

What is the transient cell population?

Lymphocytes, plasma cells, eosinophils, basophils, and neutrophils

56

Fibroblasts

Most common cell in connective tissue, synthesize fibers and ground substance, spindle shaped, may be active (fibroblasts) or inactive (fibrocytes)

57

Myofibroblasts

Involved in wound healing, has contractile filaments. Less ordered appearance in EM.

58

Fibroblasts in embryo

Cells are plump and separated by early collagen

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Adult Fibroblasts

Large oval nucleus, spindle shaped basophilic cytoplasm, active protein synthesis

60

Fibrocytes

Collagen synthesis stops, loose basophilic cytoplasm, nucleus shrinks. Flat nuclei.

61

Adipocytes

Found in CT. Store energy and have good blood supply.

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Unilocular Adipocyte

One large fat droplet. Have a signet ring appearance, with nucleus pushed to periphery of the cell. Large fat vacuole. Major energy source (TAGs)

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Multilocular Adipocytes

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.

64

Macrophages

Moved in marrow and moved to tissue. Derived from monocytes. they have an irregular cell membrane with cytoplasmic extensions. they are phagocytic (produce cytokines)..

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Kupffer Cells

Liver macrophages

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Microglia

Brain macrophages

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Osteoclasts

Bone macrophages

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Dust Cells

Lung macrophages

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Electron Micrograph Features of Macrophages

RER, prominent Golgi, lots of lysosomes, and irregular nucleus outline

70

Mast Cells

Originate in bone marrow from precursor cells lacking cytoplasmic granules. Gain cytoplasmic granules when they migrate to CT.

71

Leukotrienes

Vasoactive products of mast cells. They are released from the cell membrane of the mast cells as metabolites of arachnidonic acid

72

Mast Cell Granules

Contain histamine, heparin, chemotactic activators that attract monocytes, neutrophils, and eosinophils to site of mast cell activation

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Metachromasia

Coloring observed in mast cells due to a change in structure of the dye after binding.

74

Lymphocytes

Small, spherical (little cytoplasm), condensed basophilic nucleus, immune cells (B and T cells), B-lymphocytes develop into plasma cells

75

Plasma Cells

Synthesizes and secretes single class of immunoglobulin (glycoprotein). Basophilic cytoplasm with a soccer ball, "clock face" distribution of chromatin.

76

Eosinophils

Granules in the cytoplasm. Condensed, bilobed nucleus. Helps with phagocytosis of antibody-antigen complexes and kills parasitic worms.

77

Type V Collagen

Amnion and chorion in the fetus, makes up muscle and tendon sheaths. Doesn't form banded fibrils.

78

Reticular Fibers

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.

79

What are the three developmental stages of elastic fibers?

Oxytalan-->elaunin-->elastic

80

What makes up elastin?

Glycine, proline, desmosine, and isodesmosine

81

what are the two components of elastic fibers?

Fibrillin and elastin

82

What are the core proteins that make up proteoglycans?

Aggrecan, decorin, versican, and syndecan

83

which glycoprotein can be commonly found in the basement membrane?

Laminin

84

What stain do you use for glycoproteins and proteoglycans?

Periodic Acid Schiff

85

Mucous Connective Tissue

Few cells or fibers, mainly ground substance (jelly-like). Umbilical cord or vitreous humor in eye

86

Mesenchyme

Embryonic connective tissue

87

Loose Areolar CT

Fills the space between other tissues (large number of cells), flexible and rich in blood supply, not resistant to stress

88

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

89

Dense Regular Connective Tissue

Specific orientation of collagen fibers. Makes up tendons and ligaments. Imparts tensile strength.

90

Endotendineum

Innermost layer. CT covering each cell. Dense regular CT

91

Peritendineum

CT covers a group of cells. Dense regular CT.

92

Epitendineum

CT covers the entire tendon (outermost layer). Dense regular CT

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Reticular CT

Shorter than elastic fibers, branched, and thin

94

Elastic CT

Made of elastic fibers (yellow colored). Found in the arteries, penis, vocal cords.

95

Hypertrophic Scar

Scar is raised more than normal, but within the normal boundary

96

Keloid Scar

Scar exceeds boundary, extending into surrounding tissue. Commonly seen in people of African descent.

97

Anaphylactic Shock

Caused when there is an increased mast cell release of histamine.