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
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
3
Q
How many types of collagen are there in humans
A
28 types with 42 genes
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
5
Q
Describe the biosynthesis of collagen
A
- Synthesis on the RER
- Ribosomes synthesise collagen polypeptides
- Hydroxylation with lysine and proline
- Glycosilation
- 3 chains form the helix
- Release from the cell via a vesicle
6
Q
What is the purpose of lysine and proline hydroxylation
A
interchain H-bond formation
7
Q
Describe type IV collagen
A
network-forming collagen
Present in all basement membranes
assembles into a sheet-like network
8
Q
Describe elastin
A
Important for elasticity e.g. skin, blood vessels, lungs
Core of elastin and surface microfibrils rich in fibrillin
9
Q
Give an example of a disorder relating to elastin
A
Marfan’s
Elastic fibres cannot function due to mutations in fibrillar 1
10
Q
What is a basement membrane
A
Flexible, thin mat of ECM underlying epithelial sheets and tubes.
Muscle, nerve, fat
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
12
Q
Describe the structure of the basement membrane
A
Glycoprotein network associated with cells
Constituents - collagen IV and laminins
13
Q
Describe the structure of multi-adhesive glycoproteins
A
Large and modular
Multifunctionality due to multiple binding sites for matrix components and receptors
14
Q
Describe the structure of laminins
A
𝛼 chain, β chain, 𝛾 chain Very large (160-400 AA) and multi-adhesive
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)
16
Q
Give an example of a condition associated with laminins
A
Congenital muscular dystrophy
or
Epidermolysis bullose
17
Q
What occurs in congenital muscular dystrophy
A
Absence of 𝛼2 in laminin 2 Symptoms evident from birth Hypotonia Weakness Deformities of joints
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
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
20
Q
What is the function of fibronectin
A
Regulating cell adhesion and migration in embryogenesis and tissue repair
wound healing
continuum with actin
21
Q
What is a proteoglycan
A
Core protein with one or more glycosaminoglycan chains covalently attached
22
Q
What is a glycosaminoglycan chain
A
GAGs are long, unbranched sugars of repeating disaccharides
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
24
Q
Give an example of a glycosaminoglycan chain
A
Perlecan
Aggrecan
Decorin
Syndecans
25
Describe the structure of a GAG
1 of the 2 sugars is always amino sugar
| sulphated or carboxylate -> highly -ve
26
Describe hyaluronan
Long repeated disaccharide with NO core protein
Unsulphated
Synthesised at the cell surface
27
Describe decorin
Small proteoglycan
| Binds to collagen, essential for fibre formation
28
What is the cartilage matrix composed of
Type II collagen fibrils embedded in a network of proteoglycans
29
Describe hyaline cartilage
Abundant type of cartilage found in many places
| Cushions ends of long bones
30
What is hyaline cartilage rich in
Aggrecan
31
Describe the structure of aggrecan
```
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
```
32
What is the function of aggrecan and how is structure related
Resistance of compressive forces
| -ve charge helps retain water which is lost when compressed but then regained
33
Give an example of a disease related to proteoglycans
osteoarthritis (aggrecan)
34
Describe osteoarthritis
excessive loss of ECM so cushioning properties are lost
| Cleavage of aggrecan by aggrecanase and metalloproteinase - loss to the synovial fluid
35
Give an example of a fibrotic disorder
Liver cirrhosis
| Excessive production of fibrous connective tissue
36
Define osmolarity
Osmolarity is a measure of the concentration of all solute particles in a solution
37
Define tonicity
The strength of a solution that takes into account cell permeability
38
What makes up the university of Wisconsin solution
No sodium or chloride to prevent influx and swelling
| extracellular impermeant solutes e.g. raffinose
39
What is the name given to osmotic pressure due to plasma membranes
colloid osmotic pressure
40
Explain sliding filament theory
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
Explain the process of excitation in skeletal muscle
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
What are intercalated disks in cardiac muscle
specialised regions connecting individual cardiomyocytes
| contains numerous gap junctions for APs to spread
43
Describe excitation contraction coupling in cardiomyocytes
Same as skeletal muscle
| depolarisation opens voltage-gated calcium channels
44
What effects does calcium have in cardiac muscle
Ca2+ induced Ca2+ release by binding to RyR on SR
Initiate contraction binding to troponin
Further depolarisation
45
Describe the structure of smooth muscle
in walls of hollow organs e.g. blood vessels and the GI tract
doesn't have the regular arrangement of actin and myosin
46
Explain the process of excitation contraction coupling in smooth muscle
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
Describe endocrine signalling and give an example
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
Describe paracrine signalling and give an example
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
Describe aubocrine signalling and give an example
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
Describe signalling by membrane attached proteins and give an example
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
Describe ionotropic receptors
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
Give an example of ionotropic receptor action
nicotinic acetylcholine
Acetylcholine causing muscle contraction in skeletal muscle
GABAa (gamma amino butyric acid) causes a decreases in neuronal excitability in neurones
53
Describe G-protein coupled receptors
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
What are the 3 types of G-protein coupled receptors and what are their functions (+examples)
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
Describe enzyme-linked receptors
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
Give an example of enzyme-linked receptors
```
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
Describe type 1 signal transduction
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
Describe type 2 signal transduction
nuclear
1. hormone ligand binds
2. transcriptional regulation
59
Give an example of signal transduction
glucocorticoid
cortisol/corticosterone causes a decrease in immune response and an increase in gluconeogenesis
Thyroid hormone
T4 and T3 cause growth and development
60
What are the 4 layers of the epidermis
```
Keratinocytes
Stratum Corneum
Stratum granulosum
Stratum spinosum
Stratum basale
```
61
Describe the Stratum corneum
corneocytes (flat with no nuclei)
Protective
Filagrin gene mutation leads to eczema
62
Describe Stratum Spinosum
prickle/spinous cells that produce keratin
| Desmosomes
63
Describe Stratum Basale
Basal cells that connect to eh basement membrane
| Keratinocytes found here
64
Give some other components of the epidermis
```
Melanocytes (production of melanin)
Langerhans cells (antigen presenting)
Merkel cels (sensation)
```
65
Describe the basement membrane in the skin
Highly specialised region where epidermis meets dermis
via hemidesmosomes, anchoring plaques and proteins
Blisters are common e.g. epidermolysis bullosa
66
Describe the structure of the basement membrane in skin
hemidesmosomes
tonofilaments
demo-epidermal junctions
anchoring fibrils
67
Describe the dermis
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
Describe the subcutaneous layer
Connective tissue and fat
69
What are the two types of sweat glands found in skin
Apocrine - only located in the axillary and groins that produce discus sweat - subject to bacteria and therefore produce odour
Eccrine
70
What are the components of the dermo-epidermal junction
```
Lamina lucida
Lamina densa
Anchoring fibrils
Hemidesmosomes
Anchoring filaments
```
71
Explain the role of melanocytes and their development
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
Describe the hair follicle
```
Made up of pilo-sebaceous units
Hair follicle
Hair shaft
Erector pili muscle
Sebaceous gland
Hair bulb- blood from the dermal papilla
```
73
Describe anagen in hair growth
growth phase (85% cells)
Energy intensive + highly vascularised
Most metabolically active
Rate depends on body site
74
Describe catagen in hair growth
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
Describe telogen in hair growth
Hair is shed actively
Next anagen phase begins
Club hair takes 4-6 weeks
76
How do sex hormones affect hair growth
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
Describe the growth of nails
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
Describe the structure of the nail
Distal end is the lunula/germinal matrix (critical to growth) - white moon
eponychium - skin cover
hyponychium
onychodermal band - overhang of nail
