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Tissues Flashcards

1
Q

What are the functions of ECM

A

Physical support
Mechanical and physiochemical properties of the tissue
Influence growth, adhesion and differentiation status
Development, tissue function and organogenesis

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2
Q

What are the components of ECM

A

Collagens - I, II, III, IV
Multi-adhesive glycoproteins - fibronectin, fibrinogen, laminins
Proteoglycans - aggrecan, version, decor, perlecan

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3
Q

How many types of collagen are there in humans

A

28 types with 42 genes

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4
Q

Describe the structure of collagen

A

3 𝛼 chains in a triple helix

Every 3rd amino acid is a glycine that occupies the interior as it is the only AA small enough

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5
Q

Describe the biosynthesis of collagen

A
  1. Synthesis on the RER
  2. Ribosomes synthesise collagen polypeptides
  3. Hydroxylation with lysine and proline
  4. Glycosilation
  5. 3 chains form the helix
  6. Release from the cell via a vesicle
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6
Q

What is the purpose of lysine and proline hydroxylation

A

interchain H-bond formation

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7
Q

Describe type IV collagen

A

network-forming collagen
Present in all basement membranes
assembles into a sheet-like network

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8
Q

Describe elastin

A

Important for elasticity e.g. skin, blood vessels, lungs

Core of elastin and surface microfibrils rich in fibrillin

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9
Q

Give an example of a disorder relating to elastin

A

Marfan’s

Elastic fibres cannot function due to mutations in fibrillar 1

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10
Q

What is a basement membrane

A

Flexible, thin mat of ECM underlying epithelial sheets and tubes.
Muscle, nerve, fat

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11
Q

Give an example of a disorder relating to the basement membrane

A

Alport syndrome
Mutations n gene for type IV collagen
Basal membrane is split and laminated - filtration issues and loss of kidney function

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12
Q

Describe the structure of the basement membrane

A

Glycoprotein network associated with cells

Constituents - collagen IV and laminins

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13
Q

Describe the structure of multi-adhesive glycoproteins

A

Large and modular

Multifunctionality due to multiple binding sites for matrix components and receptors

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14
Q

Describe the structure of laminins

A 
𝛼 chain, β chain, 𝛾 chain
Very large (160-400 AA) and multi-adhesive
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15
Q

What is the function of laminins

A

Interacts with receptors such as integrins and dystroglycan

Self-associate with the basement membrane and other components (type IV collagen, proteoglycans)

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16
Q

Give an example of a condition associated with laminins

A

Congenital muscular dystrophy
or
Epidermolysis bullose

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17
Q

What occurs in congenital muscular dystrophy

A 
Absence of 𝛼2 in laminin 2
Symptoms evident from birth
Hypotonia 
Weakness
Deformities of joints
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18
Q

Describe fibronectin

A

A family of major connective tissue glycoproteins
Insoluble fibrillar matrices or soluble plasma protein
Derived from one gene where different forms arise from splicing or mRNA

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19
Q

Describe the structure of fibronectin

A 
Multi-adhesive
Large multi domain molecule
open hairpin shape/horeshoe 
Collagen, integrin and heparin binding sites 
50nm
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20
Q

What is the function of fibronectin

A

Regulating cell adhesion and migration in embryogenesis and tissue repair
wound healing
continuum with actin

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21
Q

What is a proteoglycan

A

Core protein with one or more glycosaminoglycan chains covalently attached

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22
Q

What is a glycosaminoglycan chain

A

GAGs are long, unbranched sugars of repeating disaccharides

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23
Q

Which property of GAGs contribute to function

A

Large volume to mass ratio and the hydrated gel can be very resistant to compression

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24
Q

Give an example of a glycosaminoglycan chain

A

Perlecan
Aggrecan
Decorin
Syndecans

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25
Q

Describe the structure of a GAG

A

1 of the 2 sugars is always amino sugar

sulphated or carboxylate -> highly -ve

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26
Q

Describe hyaluronan

A

Long repeated disaccharide with NO core protein
Unsulphated
Synthesised at the cell surface

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27
Q

Describe decorin

A

Small proteoglycan

Binds to collagen, essential for fibre formation

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28
Q

What is the cartilage matrix composed of

A

Type II collagen fibrils embedded in a network of proteoglycans

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29
Q

Describe hyaline cartilage

A

Abundant type of cartilage found in many places

Cushions ends of long bones

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30
Q

What is hyaline cartilage rich in

A

Aggrecan

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31
Q

Describe the structure of aggrecan

A 
GAGs are highly sulphated and present in a no. of carboxyl groups
-ve charge (sodium attracted)
Feather like structure 
Chondroitin sulfate attachment largest
Keratan sulfate attachment
Hyaluronan binding region
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32
Q

What is the function of aggrecan and how is structure related

A

Resistance of compressive forces

-ve charge helps retain water which is lost when compressed but then regained

33
Q

Give an example of a disease related to proteoglycans

A

osteoarthritis (aggrecan)

34
Q

Describe osteoarthritis

A

excessive loss of ECM so cushioning properties are lost

Cleavage of aggrecan by aggrecanase and metalloproteinase - loss to the synovial fluid

35
Q

Give an example of a fibrotic disorder

A

Liver cirrhosis

Excessive production of fibrous connective tissue

36
Q

Define osmolarity

A

Osmolarity is a measure of the concentration of all solute particles in a solution

37
Q

Define tonicity

A

The strength of a solution that takes into account cell permeability

38
Q

What makes up the university of Wisconsin solution

A

No sodium or chloride to prevent influx and swelling

extracellular impermeant solutes e.g. raffinose

39
Q

What is the name given to osmotic pressure due to plasma membranes

A

colloid osmotic pressure

40
Q

Explain sliding filament theory

A
  1. Ca2+ release -> movement of troponin from tropomyosin
  2. Exposure of the myosin binding site on the actin chain
  3. Charged myosin heads bind to the exposed sites
  4. Binding + ADP discharge causes the myosin head to pivot (power stroke), pulling the actin filament towards the centre of the sarcomere
  5. ATP binding releases myosin head from the actin chain
    ATP hydrolysis provides energy to recharge the myosin head
41
Q

Explain the process of excitation in skeletal muscle

A
  1. Action potential propagates along the myofibre membrane (sarcolemma) 7 T-tubules
  2. Depolarisation activates dihydropyridine receptors (DHPR)
  3. Conformational change in DHPR
  4. Transmission to ryanodine receptors (RyR) on sarcoplasmic reticulum
  5. Opening of RyR & release of Ca2+ from intracellular stores
  6. Depolarisation -> increase in intracellular Ca2+
42
Q

What are intercalated disks in cardiac muscle

A

specialised regions connecting individual cardiomyocytes

contains numerous gap junctions for APs to spread

43
Q

Describe excitation contraction coupling in cardiomyocytes

A

Same as skeletal muscle

depolarisation opens voltage-gated calcium channels

44
Q

What effects does calcium have in cardiac muscle

A

Ca2+ induced Ca2+ release by binding to RyR on SR
Initiate contraction binding to troponin
Further depolarisation

45
Q

Describe the structure of smooth muscle

A

in walls of hollow organs e.g. blood vessels and the GI tract
doesn’t have the regular arrangement of actin and myosin

46
Q

Explain the process of excitation contraction coupling in smooth muscle

A
  1. Depolarisation activates voltage gated Ca2+ channels
  2. Ca2+-CaM complex activates myosin light chain kinase
  3. MLCK phosphorylates myosin light chains
  4. Cross -bridges form with actin filaments -> contraction
47
Q

Describe endocrine signalling and give an example

A

hormone travels via blood vessels to act on a distant target cell
Glucagon is secreted from the pancreas travels in the blood stimulates glycogenolysis and gluconeogenesis in the liver
others: insulin acting on liver, muscle cells and adipose tissues
adrenaline from glands acting on the trachea

48
Q

Describe paracrine signalling and give an example

A

Hormone acts on an adjacent cell
insulin released by beta cells inhibits glucagon secretion in adjacent alpha cells (+endocrine)
others: NO in endothelial cells in blood vessels
Osteoclast activating factor produced by adjacent osteoblasts

49
Q

Describe aubocrine signalling and give an example

A

Signalling molecule acts on the same cell
Activated TCR initiates a cascade of reactions in the cell, expressing interleukin 2 receptor. Secretion of IL-2 also binds to IL-2 receptor on the same cell
other: acetycholine
growth factors e.g. TGFB form tumour cells

50
Q

Describe signalling by membrane attached proteins and give an example

A

plasma membrane proteins on adjacent cells interacting
APCs presenting parts of the pathogen through MHC I
circulating T cells engage with MHC molecules through TCR
others: HIV GP120 glycoprotein
bacterial cell wall components

51
Q

Describe ionotropic receptors

A

Ligand binding opens an ion permeable pore leading to a signal transduction event

  1. ligand binds to receptor
  2. change in conformation of channel
  3. pore opens
  4. movement of ions according to gradient
52
Q

Give an example of ionotropic receptor action

A

nicotinic acetylcholine
Acetylcholine causing muscle contraction in skeletal muscle

GABAa (gamma amino butyric acid) causes a decreases in neuronal excitability in neurones

53
Q

Describe G-protein coupled receptors

A

Ligand binds to activate an intracellular G-protein
1. 7-TM receptor + heterotrimeric G-protein are inactive
2. Ligand binds changing conformation of the receptor
3. G-protein binds to the receptor
4. GDP exchanged for GTP
5. G-protein dissociates into 2 active units (alpha & gamma+beta)
6. units bind
7. GTPase dephosphorylates GTP to GDP
8. alpha subunit dissociates and becomes active
Receptor is active as long as the ligand is bound

54
Q

What are the 3 types of G-protein coupled receptors and what are their functions (+examples)

A

Gs - stimulates adenyl cyclase
ATP -> cyclic AMP -> Activated protein kinase A
e.g. beta adrenergic receptor to increase heart rate

Gi - inhibits adenylyl cyclase
reduces PKA levels
e.g. Muscarinic receptor to decrease heart rate

Gq - stimulates phospholipase C
PIP2 -> IP3 + DAG -> calcium release + PKA activation
e.g. angiotensin receptor to vasoconstrict

55
Q

Describe enzyme-linked receptors

A

Ligand binds to cause clustering of receptors

  1. ligand binds
  2. receptors cluster to activate enzymes
  3. enzymes phosphorylate the receptor
  4. signal proteins bind to cytoplasmic domain
  5. recruit other signal proteins to generate the signal
56
Q

Give an example of enzyme-linked receptors

A 
insulin receptor (CD220)
insulin causes glucose uptake

ErbB
Epidermal growth factor causing cell growth and proliferation

Guanylyl-cyclase
Atrial natriuretic peptide causes vasodilation to decrease blood pressure

Ser/Thr-kinase
Transforming growth factor beta causes apoptosis

57
Q

Describe type 1 signal transduction

A

cytoplasmic
association with chaperone molecules (heat shock proteins)
1. hormone binds to receptor
2. HSP dissociates
3. 2 hormone-bound receptors -> homodimer
4. translocates -> nucleus + binds to DNA

58
Q

Describe type 2 signal transduction

A

nuclear

  1. hormone ligand binds
  2. transcriptional regulation
59
Q

Give an example of signal transduction

A

glucocorticoid
cortisol/corticosterone causes a decrease in immune response and an increase in gluconeogenesis

Thyroid hormone
T4 and T3 cause growth and development

60
Q

What are the 4 layers of the epidermis

A 
Keratinocytes
Stratum Corneum
Stratum granulosum
Stratum spinosum
Stratum basale
61
Q

Describe the Stratum corneum

A

corneocytes (flat with no nuclei)
Protective
Filagrin gene mutation leads to eczema

62
Q

Describe Stratum Spinosum

A

prickle/spinous cells that produce keratin

Desmosomes

63
Q

Describe Stratum Basale

A

Basal cells that connect to eh basement membrane

Keratinocytes found here

64
Q

Give some other components of the epidermis

A 
Melanocytes (production of melanin)
Langerhans cells (antigen presenting)
Merkel cels (sensation)
65
Q

Describe the basement membrane in the skin

A

Highly specialised region where epidermis meets dermis
via hemidesmosomes, anchoring plaques and proteins
Blisters are common e.g. epidermolysis bullosa

66
Q

Describe the structure of the basement membrane in skin

A

hemidesmosomes
tonofilaments
demo-epidermal junctions
anchoring fibrils

67
Q

Describe the dermis

A

supportive connective tissues - collagen, elastin, GAG
Thickness varies between 0.1mm and 3mm
contains fibroblasts that synthesises collagen, elastin and GAG
Dendritic cells found here

68
Q

Describe the subcutaneous layer

A

Connective tissue and fat

69
Q

What are the two types of sweat glands found in skin

A

Apocrine - only located in the axillary and groins that produce discus sweat - subject to bacteria and therefore produce odour
Eccrine

70
Q

What are the components of the dermo-epidermal junction

A 
Lamina lucida
Lamina densa
Anchoring fibrils
Hemidesmosomes 
Anchoring filaments
71
Q

Explain the role of melanocytes and their development

A

Dendritic cells in Stratum Basale
Produces melanin pigment in the melanosome, which is then packed into granules that are transferred to adjacent keratinocytes via phagocytosis
Granules form a protective cap around the nuclei to protect DNA from UV (which stimulates melanin production)
Variation in pigmentation is from no. and size of melanosomes

72
Q

Describe the hair follicle

A 
Made up of pilo-sebaceous units
Hair follicle
Hair shaft
Erector pili muscle
Sebaceous gland
Hair bulb- blood from the dermal papilla
73
Q

Describe anagen in hair growth

A

growth phase (85% cells)
Energy intensive + highly vascularised
Most metabolically active
Rate depends on body site

74
Q

Describe catagen in hair growth

A

Cell devision slows and stops
End of shaft keratinises to form a club shape
Dermal papillae and club moves to the base of muscle insertion

75
Q

Describe telogen in hair growth

A

Hair is shed actively
Next anagen phase begins
Club hair takes 4-6 weeks

76
Q

How do sex hormones affect hair growth

A

testosterone on the follicles
There is a surge during puberty which grows terminal hair
Pubic and axillary, then beard and chest, then nose and ear hair
Androgen sensitivity - balding pattern

77
Q

Describe the growth of nails

A

Fingernails - 3mm a month
Toenails - 1mm a month
Nails grow from the Germinal matrix
Due to adhesion and nail folds, the nail grows out and not up
Nail surface is produced by the proximal nailbed

78
Q

Describe the structure of the nail

A

Distal end is the lunula/germinal matrix (critical to growth) - white moon
eponychium - skin cover
hyponychium
onychodermal band - overhang of nail

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