Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Molecules and cells in human disease > Connective Tissue Disorders > Flashcards

Connective Tissue Disorders Flashcards

You may prefer our related Brainscape-certified flashcards:
Organic Chemistry 101 flashcards
1
Q

What are complex tissues organised by?

A

the ECM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what’s bigger, the ECM or the cells it organises?

A

the ECM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what are basement membranes?

A

specialised ECM to organise epithelial cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

how are different parts of ECM derived?

A

distinct arrangements of collagen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

which type of collagen is specific to basement proteins?

A

collagen IV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what structure does collagen IV assemble into?

A

a 2D net

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

why does collagen IV assemble into a net not fibres? (4)

A
  • non collagenous regions aren’t cleaved- so can’t pack parallel
  • crosslinking of 4 triple helices to form a colied coil
  • interuption in Gly-X-Y repeats cause flexibility
  • there’s end-end interactions between the non collagenous ends
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

describe the creation of collagen IV?

A

made in ER
each chain made then co-transitionally transported through the ER
asseembles into 3 molecule triple helix - driven by C-terminal non-collagenous domain
- the trimers interact to form a hexamer (2x3)
at the 7S domains there’s a central interaction to form a tetramer of trimers
- lattice builds of these to form BM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

how many collagen IV gnes?

A

6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what are the 3 possible trimers of collagen 4 possible?

A

a1 a1 a2
a3 a4 a5
a5 a5 a6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what is glomerular BM?

A

filter of glomerules in kidneys
a particularly thick BM
fluid pushes through to give urine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what trimers are used in kidney BM?

A

in development it’s a1 a1 a2
as it matures it switches to
a3 a4 a5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what collagen trimers are used in most tissue?

A

a1 a1 a2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what is alports syndrome?

A
  • loss of a3 a4 a5
    patients are fine/healthy in childhood as modt tissues are a1 a1 a2
    a3 a4 a5 has more cross links, making it more restiant to pressure- so in alports syndrome, adult kidneys have glomerular Bm degradation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what causes early onset alports?

A

large gene rearrangements

non-sense mutations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what causes late onset alports?

A

missense mutations, disrupt gly-x-y repeats

condensed cysteine reduces crosslinking

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is laminin?

A

a major component of BMs that self-assembles into a network to present binding sites for cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what’s laminin made up of?

A

3 chains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what are the 3 chains that make up laminin?

A

a, B, y

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what shape does the laminin take?

A

cruciform

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

describe the structure of laminin?

A

3 chains form a coiled coil shape
brought about by repeated sequence of 7 Amino Acids
disulphide links beween each end of coiled- coil domains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what’s similar between collagen IV and laminin networks?

A

they form spontaneously in vitro

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

how is the laminin and collagen network linked?

A

by accessory molecules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

are there more laminin or collagen isoforms?

A

laminin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

how many of each laminin chain are there?

A

5a, 3B, 3y

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

are all laminins essnetial through the body?

A

no- only some- these are ubiquitous

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what does the diversity of laminin isoforms results in (pathologically)?

A

a range of tissue specific genetic diseases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

what’s pierson syndrome?

A

rare lethal condition
lack of laminin II (which is usually found in glomerular BM, eye and synaptic BM) causes renal disease, eye abnormalities and muscular issues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

what do specific laminin isoforms in the epidermis link?

A

to the underlying collagen in the dermis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

what is Epidermis Bullosa?

A

a related group of conditions where skin blisters following mechanical trauma
mutations affect mechanical strength or dermal-epidermal junction

31
Q

what isoform is laminin 5?

A

a3:B3:y2

32
Q

what does laminin 5 do in BM?

A

links cell surface adhesion proteins (integrins) in structures called hemisomes to underlying collagen

33
Q

what does mutation of laminin 5 cause?

A

junctional epidermis bullosa

34
Q

what is junctional epidermis bullosa?

A
  • lethal within first few months after birth
  • recessive mutation
  • mice model-normal phenotype at birth, develop blisters and die by day 3
35
Q

what can cause defect in laminin 5?

A

mutation in laminin B3

36
Q

what does gene therapy for laminin B3 chain mutation do?

A
  • uses retrovirus to deliver functional Laminin B3 gene to patients
  • causes skin healing
37
Q

what do cell surface receptors for laminin link?

A

epithelial cells to the basement membrane

38
Q

what are integrins?

A

cell- ECM adhesion receptors found in most cells

39
Q

what does deletion of B4 integrin lead to?

A

same phenotype as Laminin 5- not living long past birth

40
Q

what’s Epidermis bullosa simplex?

A
  • milder than other forms
  • blisters from mechanical stress
  • heals w/o significant scarring
  • less lethal than junctional EB
  • associated with mutations in keratin 4+5
41
Q

what tissues are BMs found in? (5)

A
  • kidney glomerulas
  • epithelium
  • muscle
  • blood vessel
  • neuromuscular junction
42
Q

muscles transmit force via

A

a secure attachment to BM

43
Q

what laminin isoform is in muscle-tendon BM?

A

laminin 2 (a2:B1:y1)

44
Q

what laminin isoforms are in neuromuscular junctions?

A

laminin 2 (a2:B1:y1) and (a5:B2:y1)

45
Q

overall what are muscular dystrophies?

A

defects in muscle attachment to BM

46
Q

how many main ways does the BM attach to muscle?

A

2

47
Q

what are the 2 ways the BM attaches to muscle?

A

1) Laminin (BM)–> Integrin (cell)

2) Laminin (BM) –> Dystroglycan (cell)

48
Q

which parts of the BM- cytoskeleton linkage can have disruptions to cause MD? (5)

A
  • Lamin
  • integrin
  • dystroglycan
  • collagen
  • dystrophin
49
Q

what type of dysfunction leads to congenital MD?

A

laminin

50
Q

what type of dysfuncction leads to Duchenne/ Becker MD?

A

dystrophin

51
Q

which type of dysfunction leads to bethlem MD?

A

collagen

52
Q

compare the phenotype of duchenne and becker MD

A

Duchenne- onset childhood, wheelchair by 10 years, death 30s

Becker- childhood onset, wheelchair by 40s, normal death age

53
Q

is there a cure for MD?

A

no

54
Q

what causes 50% of congenital MDs?

A

Laminin a2 chain mutation

55
Q

when do congenital MDs manifest?

A

after birth/ first few years

56
Q

what are the symptoms of congenital MD? (4)

A

muscle weakness
delayed motor development
joint problems
PNS and CNS defects

57
Q

is the phenotype of congenital MD worse or better if there’s a complete loss of laminin a2 as opposed to partial loss?

A

worse

58
Q

what type of gene inheritance is congenital MD?

A

autosomal recessive

59
Q

what does loss of Integrin a7 cause?

A

progressive MD

60
Q

what does loss of integrin B1 cause?

A

no MD

61
Q

does the dystrophin complex function with or independently of the laminin- integrin complex?

A

independent

62
Q

what’s the most common type of MD?

A

Duchenne

63
Q

what type of gene inheritence in duchenne MD?

A

X-linked

64
Q

what component is affected in duchenne?

A

dystrophin

65
Q

if there’s issues with both dystrophin and integrin would the phenotype be worse than one on its own?

A

yes

66
Q

what’s the difference between duchenne and becker MD?

A

Duchenne is caused by a complete loss of dystrophin

Becker is caused by a partial loss of dystrophin

67
Q

how big is the dystrophin gene?

A

very large- largest in genome

68
Q

is it possible to deliver a dystrophin gene by a retrovirus like laminin B3?

A

no- too big

69
Q

how can duchenne symptoms be reduced to becker like?

A

further cutting of gene

70
Q

are there any known mutations of dystroglycan?

A

no- probably not viable (however MDs are associated with it)

71
Q

what is Fukuyama Congenital MD?

A
  • predominant in Japan
  • severe muscle degeneration
  • brain abnormalities
72
Q

what causes Fukuyama congenital MD?

A

insertion into Fukutin gene
Fukutin associated with glycosylation of dystroglycan
can’t bind to laminin w/o

73
Q

what causes the degenerative aspect of MD?

A

defective control of apoptosis- overactivation of apoptotic factors

74
Q

how can apoptosis be reduced in MD?

A

loss of Bax/ BCL-2

Molecules and cells in human disease (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions