Connective Tissue Flashcards

1
Q

What are the 2 main components that make up connetive tissues?

A

Cells and the extracellular matrix

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2
Q

What are resident cells?

A

Originates in connective tissue like fibroblast or spends most of life in connective tissue like mastocyte.

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3
Q

What are migrating cells?

A

Arrive in connective tissue from blood under specific conditions, e.g. inflammation.

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4
Q

What ground substances are present in the intercellular matrix?

A

GAGs
Proteoglycans
Glycoproteins

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5
Q

What fibers are present in the intercellular matrix?

A

Collagen

Elastic

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6
Q

Distinguish the different types of extracellular matrix.

A

gelatinous; solid; liquid

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7
Q

Where do connetive tissues originate from?

A

Connective tissue originates from mesoderm.

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8
Q

What is the mesenchyme?

A

The mesenchyme is the connective tissue of the embryo. It contains very fine and sparse collagen fibers and abundant ground substance and cells.

The collagen fibers reflect that this connective tissue does not undergo intensive mechanical stress.

It’s also the progenitor of all cells of connective tissues.

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9
Q

Describe the features of fibroblasts.

A

Metabolically active cells with basophilic cytoplasm which actively synchronise and shape the extracellular matrix.

Synthesis of all components of the intracellular substance.

Most common cells of the connective tissue.

When needed, they can become mobile and proliferate.

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10
Q

Describe the size and components of fibroblasts.

A

Length 12-14μm; width 5-7μm

Can be seen under a light microscope.

There is an abundant GA and ER associated with ribosomes inside the cell.

Abundant heterochromatin indicates active transcription.

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11
Q

What happens when fibroblasts become fibrocytes?

A

The shape of cell changes and the amount of ER and GA decreases, thus the cell becomes less active.

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12
Q

What is a reticular cell?

A

The reticular cell is a type of fibroblast that synthesizes type II collagen and uses it to produce reticular fibers.

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13
Q

What are the functions of white fat cells?

A

Energy storage sites

Insulation - particularly relevant when adipocytes associate to form adipose tissue.

Cushioning - involves adipose cells.

Endocrine functions

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14
Q

Where are white fat cells located?

A

Commonly found in scattered groups in loose connective tissue.

In some areas, they can form a true tissue called the adipose tissue.

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15
Q

Describe the structure of white fat cells and how this is formed.

A

Through a multistep differentiation process, a lipoblast (adipoblast) is formed in which small droplets containing 3 glycerides are evident.

These droplets fuse to form a single big droplet which occupies the whole cytoplasm. They are not surrounded by a true membrane, but a phospholipid monolayer with polar heads towards the cytoplasm.

Then the cytoplasm is confined at the peripheral as a thin layer containing the organelles and the nucleus.

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16
Q

Describe the appearance of white fat cells in a histological section, explain why it takes this appearance.

A

In a histological section, fat cells appear empty except from the visible thin cytoplasm ring.

This is because of the lipid content of droplets being extracted by treatment with alcohol (dehydration) for preparation for paraffin.

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17
Q

Describe the proliferative abilities of white fat cells.

A

Adipose cells have limited proliferation ability in adult cells.

They proliferate during the 1st year of life and we live life with a number of cells set at 3 or 4 years of life.

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18
Q

Why can white adipose cells be considered endocrine cells?

A

They produce the hormone leptin, which is important as shown in mice. If its activity is abolished, the mice lose sense of safety and continuously eat until obesity.

Therefore leptin signals to the hypothalamus a sense of safety.

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19
Q

What are the functions of brown fat cells.

A

They are involved in thermoregulation, forming brown fat tissue and are abundant in hibernating mammals.

In humans, they are abundant in newborns that do not shiver in order to maintain body temperature.

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20
Q

Describe the structure of brown fat cells.

A

Their cytoplasm is filled with many small lipid droplets instead of one big one, they also have a high number of mitochondria.

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21
Q

How do brown fat cells regulate temperature?

A

In mitochondria a protein called UCP catalyzes re-entry of protons into the matrix, thereby reducing the synthesis of ATP while generating heat.

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22
Q

Where are macrophages derived from?

A

They are derived from circulating monocytes which leave the bloodstream and differentiate into macrophages.

In connective tissue proper they are also called osteocytes.

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23
Q

What are the receptors on phragocytes that recognises bacterial presence?

A

TOLL-like, Fc and C3b.

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24
Q

Describe TOLL-like receptors.

A

TLR(TOLL-like receptors) are single membrane spanning receptors able to recognize specific antigens common to several pathogens, their binding activates internal signalling, which leads to the expression of membrane proteins and eventually the activation of t-lymphocytes.

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25
Q

Describe hoe Fc receptors contribute to phagocytosis.

A

Macrophages also use receptors for the Fc portion of antibodies. The antibodies recognise and bind to microbes leading to microbe opsonization.

The variable fragment binds and decorates the microbe. Fc fragments are free for binding to macrophage, their binding activates the macrophage, which internalizes the opsonized microbe into phagosome and fuses with lysosomes making phrag-lysosome.

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26
Q

What are complement components?

A

The complement component is a group of plasma proteins usually in an inactive form, and becomes activated with the presence of a foreign body by a cascade mechanism and binds to a target.

This causes either its lysis and/or recognition by phagocytes.

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27
Q

How do complement components work?

A

Complement components can bind to the membrane of the pathogen and form MAC (Membrane Attack Complex), this makes holes in the PM, disrupting the integrity and eventually leading to death.

Otherwise it can bind to complementary receptors on macrophages and activate phagocytosis.

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28
Q

How so macrophages respond to large foreign bodies?

A

If foreign body is large, macrophages can fuse to form a giant poly-nucleated cell.

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29
Q

Describe the functions of macrophages.

A

Innate immunity (chemotaxis/phagocytosis)

Presentation of antigens to T-helper lymphocytes (MHC-II) - allows macrophage to expose specific antigens derived from foreign bodies presented to T-lymphocytes.

Synthesis and release of substances in inflammation, e.g. prostaglandins or necessary to the activation of lymphocytes, e.g. IL-1.

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30
Q

How do macrophages present antigens?

A

Part of the pathogen is exposed by the macrophage, antigens are recognised by CD4 T-helper cells which starts immune response.

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31
Q

Why are some other cells from different tissues considered part of the macrophage family?

A

They are:

Same origin from monocytes
Phagocytic capacity
Ability to present antigens to lymphocytes by complex MHC-II(APC cells)
Receptors for Fc region of antibodies

32
Q

Describe the shape and size of mastocytes.

A

Round or spindle-shaped cells of large diameter (up to 20-30 μm).

33
Q

Describe the structure of mastocytes.

A

‘Stuffed cell’ - cytoplasm completely stuffed with granules.

Have numerous granules in cytoplasm containing heparin (inhibits activation of the coagulation cascade) and histamine (vasodilator at capillary level / increased capillary permeability).

The granules are metachromatic - a property to appear stained of a colour different from the dye used, occurs in this case using dyes of the toluidine family.

Basophilic cytosol.

34
Q

What are the functions of mastocytes?

A

Inflammatory reactions

They are mainly responsible for allergic reactions, i.e. Anaphylactic shock.

35
Q

Describe the general features of ground substances.

A

Transparent material forming a semi-fluid gel.
Slightly PAS + due to glycoproteins.
Composed of water (80-90%) with various solutes, proteoglycans and glycoproteins.
Can be stained in cryosections using Alcian blue for presence of GAGs.
Can be metachromatic due to presence of GAGs.

36
Q

What are glycosaminoglycans?

A

Polysaccharides formed by disaccharide units containing COO- and SO3- groups repeated thousands of times.

Acidic molecules (-charged) for the presence of carbonyl groups and sulphate in disaccharide units.

37
Q

Describe hyaluronic acids.

A

Hyaluronic acid is a type of GAGs. They are often used as fillers, and are the largest GAG.

They are combined with a large amount of water to form a thick gel, which is important for specific functions.

38
Q

What are proteoglycans?

A

Macromolecules formed by protein and GAGs.

39
Q

What are the functions of proteoglycans?

A

Regulate flow of water and solutes.

Confer to the tissue resistance to compression.

40
Q

Describe fibronectin.

A

Big proteins formed together by 2 subunits bound together by disulfide bonds.

Different domains recognised specifically involved in binding components of extracellular matrix or integrins on cell.

Integrin fibronectin binding occurs to a specific sequence called RGD.

RGDs are present on fibronectin and recognised by integrins that mediate cell attachment.

41
Q

Describe lamini.

A

A big glycoprotein in extracellular matrix.

Several domains can be identified.

Abundant in the basal membrane.

Integrins binding to laminin generates signals to the cytoplasm which activates important selectivities, e.g. organisation of cytoskeleton.

42
Q

What are the types of fibers present in the intracellular matrix?

A

Collagen
Reticular - made of a specific type of collagen.
Elastic

43
Q

What are the functions of collagen?

A

Structural strength for connective tissues.

The dermis is responsible for providing tone, hydration and contributing to structural quality.

Gives resistance to bones, tendons, ligaments and aponeurosis.

44
Q

Describe the appearance of collagen with various staining techniques.

A

In masson’s trichrome stain, the colours are light blue due to aniline blue dye.

In the mallory staining, fiber dark blue due to mixture of aniline blue and orange G.

While in H&E staining, collagen fibers stained by eosin.

45
Q

How do fibers appear under polarized microscopes?

A

Under polarized microscopes, the fibrils are birefractive, indicating that they are formed by thinner filamentous units that can’t be visualized under the LM.

46
Q

How do fibers appear under TEM?

A

Under TEM, the fine fibrils are visible and are 20-100 nm.

They present a transverse striation due to alteration of light and dark bands of 64-70 nm, this difference is caused by whether they are dried.

47
Q

What is each fibril made up of?

A

Each fibril is made up of 5 protofilaments made of a protein called tropocollagen.

Multiple tropocollagen molecules join together to form protofilaments which associate together to form fibrils.

48
Q

What is tropocollagen made up of?

A

The tropocollagen molecule is made of 3 alpha helix chains that coil together.

A single molecule has a 300 nm length and 1.5 nm diameter with a head and tail orientation.

There is frequent presence of hydroxyproline, proline and glycine.

49
Q

Describe the organisation of tropocollagen molecules.

A

Single tropocollagen molecules are organised head to tail for the protofilament molecules.

The tropocollagen are organised staggered to each other in each row by 1/4th of their length.

50
Q

Why do fibrils show dark and light bands under TEM?

A

The dark light bands observed are the result of the staggered formation of tropocollagen molecules.

The osmium used as a contrasting agent deposits more on the 30 nm gaps, therefore the dark bands correspond to where there are gaps in between the tropocollagen.

51
Q

Break down the structure of tendon to tropocollagen molecules.

A

A tendon is a bundle of parallel collagen fibers.

Fibres can be separated in single fibres, then in fibrils, microfibrils, protofilaments and single tropo protein molecules.

52
Q

Why do collagen fibers have strong tensile strength?

A

They can be slightly extended due to:

Presence of intramolecular cross-links.
Covalent bonds within the tropocollagen molecules.
Bonds between adjacent tropocollagen molecules to the level of the terminal telopeptides.

These bonds are formed due to the presence of lysine, hydroxylysine and hydroxyproline.

53
Q

How is collagen formed?

A
  1. In the ER/GA, the pro-alpha chain is synthesised, there is the hydroxylation of proline and lysines; glycosylation of selected hydroxylysines.
  2. 3 alpha helices self assemble, forming a procollagen. They have propeptides at the end.
  3. Procollagen is packed into secretory vesicles and secreted. Propeptides are removed by a procollagen peptidase present on the PM.
  4. The collagen molecules self assemble to first form protofilaments, then fibrils and fibers.
54
Q

What kinds of cells secrete collagen?

A

The cells which secrete collagen may be fibroblas, osteoblast, chondroblast, odontoblast and even smooth muscle cells.

55
Q

What happens if the propeptides are removed too early during collagen formation?

A

If propeptides are removed before secretion, the cells would be seriously damaged by the formation of collagen fibers.

56
Q

How can fibrillogenesis be quantified?

A

It’s possible to quantify fibrillogenesis by measuring the amount of propeptides in blood/urine.

It’s also possible to quantify telopeptides as an index of bone resorption.

57
Q

Describe the structure of collagen IV.

A

Non-fibrillar
Tropocollagen molecules assemble head to head to form dimers.
4 dimers assemble to form a tetramer which associates to make nets.

58
Q

Where is collagen IV present?

A

They are present in the basal membrane.

59
Q

What collagens are associated to type I and II collagen? What is their function?

A

Type IX associate to type II in the cartilage matrix. Type VI associate with type I.

They are important for fibril and fibril interaction as well as mediating interaction of the fibrillar collagen with other components of the intracellular matrix.

60
Q

Describe the condition of scurvy.

A

This is an acquired condition.

This is due to lack of vitamin C, which is a fundamental cofactor for activity of hydroxylases. This is responsible for hydroxylation of lysines and prolines and this activity will be reduced or abolished if vitamin C levels are too low.

Consequently this causes a lack of intermolecular formation of crosslinking and thus fragile collagen fibers. The condition particularly affects gums with lost teeth.

61
Q

What structure does collagen III form?

A

Collagen type III forms reticular fibers, which are thinner fibrils than collagen I and II.

62
Q

Where are collagen IIIs found?

A

Collagen type III is abundant in liver and lymph node stromas as well as other lymphoid organs.

It’s also abundant in embryonic connective tissue, and adult connective tissue during wound repair.

63
Q

Describe the staining procedure of collagen III.

A

The reticular fibres are not stained by routine dyes like haematoxylin and eosin.

They can be stained by silver stain, which highlights reticular fibers by using silver solutes to impregnate the fibers called argyrophilic fibers.

64
Q

What pathological condition can a mutation of collagen III lead to?

A

Mutations in collagen III can lead to a form of Ehlers-danlos syndrome.

The symptoms include hypermobility of joints, hyper extensivity of skin and fragility of wall of blood vessels.

65
Q

Describe the general features of elastic fiber (yellow fiber).

A

Extends with force
Thickness between 0.2-0.5 μm.
Needs to be stained with specific dye under LM.
Formed by 2 proteins - elastin and fibrillin.

66
Q

Describe the structure of elastic fiber.

A

In a mature fiber, elastin forms the core surrounded by fibrillin microfibrils.

There are other proteins that co-purify and are associated with fibrillin.

67
Q

What are the functions of elastic fiber?

A

Fibrillin microfibrils are able to mediate cell signalling via receptors and are able to sequester members of the TGF𝛃 family of growth factors. By doing this they can store these factors in the extracellular matrix.

Accommodate stretching forces to allow specific tissues to sustain stretching.

68
Q

Describe the monomers that make up elastic fibers.

A

Elastin is formed by association of monomers of tropoelastin, which contains 2 unusual amino acids - desmosine and isodesmosine, which are responsible for the formation of cross-linking of elastin molecules.

Contains a lot of glycine and proline, but very little hydroxyproline and no hydrolysis.

Glycerin randomly distributed, giving overall hydrophobicity. Stretching forces hydrophobic regions to get in contact with water. When removed, hydrophobic regions get together and exclude water, bringing fibers to its original conformation.

69
Q

How does elastin interact with microfibrils to form elastic fibers?

A

Elastin deposits on the surface of microfibrils. As deposition proceeds, microfibrils are mostly pushed to the peripheral.

70
Q

Are microfibrils present in blood vessels?

A

Fibril microfilaments not present in elastic sheets of the arteries.

71
Q

Which types of cells produce elastin?

A

Elastin is mostly produced by fibroblast but smooth muscle cells are also responsible for elastin deposition in the blood vessels.

72
Q

How long does the production of elastin last?

A

Production of elastin is not continuous over life, most produced up to puberty, slows down after that and stops after 40.

73
Q

What 3 critical functions are elastic fibers responsible for in elastic arteries?

A

Elastic recoil - ability to stretch and return to initial caliber.

Regulation of growth factors which are involved in vascular assembly and maintenance of vessel wall integrity.

Regulation of smooth muscle cell behaviour - fibers contain cell attachment motifs which affect adhesion, migration, proliferation, differentiation and survival of cells.

74
Q

Why do tissues lose elasticity?

A

Tissues lose elasticity as they are not replaced in adults leading to aging and contributes to wrinkle formation, which can’t be repaired.

75
Q

Describe Marfan syndrome.

A

A pathological condition in which elastic fibers are affected. Fibrillin is affected, most carry mutation in the gene with FBN1. This is characterized by a tall stature, long trunk, short legs, long fingers and toes.

The cardiovascular system is particularly affected, as well as skeletal and ocular.