Brainscape's Knowledge GenomeTM

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


See full index

Molecular Basis Of Disease > Skin And Extracellular Matrix > Flashcards

Skin And Extracellular Matrix Flashcards

1
Q

What is the cause Pemphigus

A

Antibodies attack cadherins and integrins in keratinocytes causing defects in cell to cell and cell to matrix adhesion

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

Key feature of Pemphigus and main types of the disease

A

Blisters on skin and in oral cavity

Two types:

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

Molecular basis of Pemphigus Volgaris

A

Autoantibodies attack cell surface antigens (desmogleins 1 and 3 - cadherins)

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

Symptoms and treatment of pemphigus vulgaris

A

Symptoms:

  • intra-epidermal blisters (above dermis) which can rupture
  • when ruptured causes bleeding and fluid leaking
  • proteolytic enzymes produced breakdown enzymes in these cells

Treatment:

  • immunosuppressive agents
  • corticosteroids (decrease inflammation)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is a key identifying feature in the histology of Pemphigus vulgaris

A

Tombstone rows

- due to single layer of basal cells still attached to dermis of skin

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

Molecular basis of Bullosa Pemphigoid

A

Autoantibodies attack BP 180 and BP 230 (basement membrane proteins) which connect hemidesmosome to intermediate filaments

Skin keratinocytes cannot attach to basement membrane

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

Symptoms and treatment of Bullosa Pemphigoid

A

Sub-epidermal bullae (blisters)

Blisters which appear on:

  • abdomen
  • groin
  • upper thighs
  • arms
  • along creases in skin (e.g. inner elbow joint)

Treatment:
- immunosuppressants or steroids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is keratin and what is it’s function?

A

Intermediate filament which forms alpha helices or beta sheets

Functions:

  • hold epithelial cells together through cell junctions
  • provides mechanical strength at hemidesmosomes and desmosomes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Keratin structure

A

Elongated molecule which N terminus (head) and C terminus (tail)

Composed of subunits
- Type 1 subunit pairs (acidic)
- type 2 subunit pairs (basic)
Different subunit compositions are expressed in different tissues

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

Keratin subunits expressed in epithelium

A 
Basal layer (stratified epithelia) 
- keratins 5 and 14 
Suprabasal layers (layers above the basal layer) 
- keratins 1 and 10
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Intermediate Filament assembly

A
  1. keratin polypeptide
  2. Another keratin monomer comes and coils with the first monomer to create a dimer
  3. Another dimer is created and joins with the first creating a tetramer
  4. Happens continuously until a protocol amend is formed
  5. Eight tetramers are then twisted into a rope like filament
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the main cause of Karen in associated disease

A

If either one of a keratin pair is lost

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

What are the two keratin associated diseases

A

Epidermolysis bullosa

Epidermolysis hyperkeratosis

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

Epidermolysis bullosa simplex symptoms

A

Blisters due to skin not being able to resist mechanical stress

  • blisters appear primarily on hands and feet
  • can usually heal without scarring
  • sever cases have widespread blisters which can lead to secondary infections and dehydration

Mostly appears in infants and children

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Molecular basis of Epidermolysis bullosa simplex

A

Genetic mutations = KRT5 or KRT14 genes

KRT14 mutation = non functioning keratin 14 molecule
KRT5 mutation = unstable keratin protein
Phenotype = keratin clumping or disorganised filaments

Because they are expressed in basal cells epidermis separated from dermis

Severity depends on type of mutations

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

Epidermolysis hyperkertosis symptoms and genetic inheritance

A

Symptoms in infants:

  • very red skin (erythroderma)
  • severe blisters

Symptoms in adults:

  • skin thickening
  • blisters and erythroderma less frequent

Genetic inheritance:
Autosomal dominant

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

Pathophysiology of epidermolytic hyperkeratosis

A

Mutations in KR1 and KR10

  • keratin aggregates in suprabasal cells (stratum corneum)
  • loss of strong intermediate filaments
  • increase in mitosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Other keratin disorders

A

Keratin 6 and 16 mutations
- hair and nail disorders

Keratin 3 and 12 mutations
- cornea defects

Epidermodysplasia verruciformis (tree man)

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

Epidermodysplasia verruciformis symptoms, genetic inheritance

A

Autosomal recessive hereditary disorder

Symptoms:

  • wart like growths
  • scaly macules and papules
  • on hands and feet
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Epidermodysplasia verruciformis molecular basis

A

Loss of function mutations in EVER1/TMC6 or EVER2/TMC8 (chromosome 17)

  • code for membrane proteins which forms a complex with zinc transporter protein in ER membrane of keratinocytes
  • these proteins also act as restriction factors for EV-specific HPV in keratinocytes (limit access of zinc to viral proteins) without the genes it increases risk of HPV
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the ECM and what is its function?

A

Network of proteins and polysaccharides

The ECM influences cell:

  • growth
  • movement
  • shape
  • proliferation
  • survival
  • development
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Which cells produce the ECM?

A

Fibroblasts

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

What is the ECM composed of?

A

3 major macromolecules:

  1. Proteoglycans and glycosaminoglycans (GAGs)
    - produce polysaccharide chains
  2. Fibrous proteins
    - help with structure
    - collagen for strength and elastin for stretch
  3. Glycoproteins
    - helps with adhesion
    - fibronectin (helps adhere fibroblasts to matrix)
    - laminin (adhere epithelium to basal lamina)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the basal lamina and what are its macromolecules components?

A

Specialised ECM which lies beneath epithelial cells

Components:

  • laminin to adhere
  • type 4 collagen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Glycosaminoglycan (GAG) structure

A

Unbranched polysaccharide chains of repeated disaccharides

Disaccharide:

  1. Always an amino sugar (N-acetylglucosamine or N-acetyalgalactosamine)
  2. Always uronic acid

Sulphate in most cases (has a sulphate group on each block

26
Q

Glycosaminoglycan (GAG) chemical features

A

Hydrophilic (likes water)

Negatively charged

  • attract positive ions (Na) in water
  • form hydrated gels

Helps withstand compressive forces (swelling)

27
Q

What are proteoglycans and what is it’s structure

A

A proteoglycan are Glycosaminoglycan (GAG) covalently linked to a protein

Structure:
Protein - linkage tetrasaccharide - GAGs

28
Q

Types of Proteoglycans and their main functions

A

Decorin:

  • 1-10 GAG chains
  • influences fibrillogenesis
  • assists in assembly of collagen fibrils

Aggrecan:

  • 100 GAGs
  • resists compression

Ribonuclease (RNase)
- catalyses degradation of RNA into smaller components

29
Q

Proteoglycan Functions

A

Mechanical

Filter
- regulate molecules getting in and out of the cell by charge or size

Chemical signalling (syndecans) 
- bind to growth factors for cell growth and proliferation

Regulate protein or enzyme activity

30
Q

4 classes of proteoglycans

A

Intracellular

Transmembrane

Pericellular

ECM

31
Q

Where is collagen produced? Where is it mostly found?

A

It’s a fibrous protein secreted by fibroblasts

Major component in hair and skin (can lasts up to 10 years compared to other proteins)

32
Q

What are the classes of collagen?

A
  1. Fibrillar collagens
  2. Fibril-associated collagens
  3. Network forming collagens
33
Q

Fibrillar Collagen Class

  • types
  • where is it found
A

Type 1,2,3,5,11

Found in:

  • skin
  • bone
  • tendons
  • ligaments
  • cornea
  • organs
34
Q

Fibril-associated class collagens

  • types
  • where is this found
  • function
A

Type 9 and 12

9 - cartridge and cornea
12 - tendons and other tissues

Function: link Fibrillar collagens together

35
Q

Network Forming class of collagens

  • types
  • where is it found/function
A

Type 4 and 7

4 - form mesh networks in the basal lamina
7 - anchoring

36
Q

Collagen structure

A

Long, stiff, triple stranded helix

3 collagen alpha chains wound together

  • 42 types of alpha chains
  • 40 combinations of different alpha chains wound together

Rich in proline and glycine

37
Q

Synthesis and secretion of collagen pathway

A
  1. Synthesis of pre collagen alpha chains on ribosomes
  2. Hydroxylation of proline and lysine
  3. Release from ribosome and glycosylation of selected hydroxylysines = pro collagen
  4. Formation of triple helix and folding of globular domains
  5. Secretion from cell
  6. Remove pro-sequences from N and C terminals = tropocollagen
  7. Deamination of lysine residues to form aldehyde cross links = collagen
  8. Aggregation and self-assembly into collagen fibrils which make collagen fibres
38
Q

How is collagen organised

A

In bundles

39
Q

What is the purpose of elastin

A

For tissues to stretch and recoil

40
Q

What is the chemical components and features of elastin

A
  • 750 amino acids
  • hydrophobic (don’t like water)
  • rich in proline and glycine (not glycosylated)
  • loose random coil formation
41
Q

How is elastin synthesised?

A
  1. Tropoelastin is secreted into extra cellular environment
  2. These become cross linked to form elastin fibres
  3. Networks of these fibres come together to make a sheet
  4. These sheets are then covered with microfibrils
42
Q

Common disorders of the extra cellular matrix

A
  • arthritis
  • scurvy
  • Marian syndrome
  • osteogenesis imperfecta
  • chondrodysplasias
  • Euler see-Danilo’s syndrome
43
Q

What is arthritis and what are the 2 types?

A

Irreversible destruction of cartilage, tendon and bone

Types:

  1. Rheumatoid arthritis (autoimmune disease)
  2. Osteoarthritis (due to injury)
44
Q

What macromolecules are found in cartridge?

A

Proteoglycans and type 2 collagen

45
Q

Which joints are mostly affected by osteoarthritis?

A

Hip
Hand
Foot
Knee

46
Q

What are some features of rheumatoid arthritis in the knee joint?

A
  • subchondral cysts and sclerosis (bone hardening)
47
Q

Difference between osteoarthritis and rheumatoid arthritis in synovial joints

A

Osteoarthritis:
- thinning of cartridge which leads to bone ends rubbing together

Rheumatoid:
- synovial membrane becomes inflamed which causes bone erosion

48
Q

Rheumatoid arthritis aetiology

A
  1. Due to the inflammation of synovial membrane inflammatory cytokines (TNF alpha and interleukins) are released
  2. This stimulates the production of matrix metalloproteinases (MMP’s) which degrade the ECM
    - MMP 13 plays a key role
49
Q

Collagen related disorders

A
  • Ehlers-Danilo’s syndrome
  • scurvy
  • Chondrodysplasias
  • osteogenesis imperfecta
50
Q

Scurvy symptoms

A
  • swelling and bleeding of gums
  • easily bruised and bleeding
  • pain and swelling of joints
  • hair and tooth loss
  • small bleeding around hair follicles and under nails
  • fatigue
  • dry and pale skin
51
Q

Scurvy Aetiology

A

Vitamin C deficient

Vitamin C needed for collagen processing (proline and lysine hydorxylation)
- without this pro-collagen alpha chains degrade

Leads to:

  • fragile blood vessels (explains the bleeding)
  • loose teeth
52
Q

Osteogenesis imperfecta aetiology

A

Results from mutations in collagen 1 gene
- collagen 1 needed for skin, tendons and bones to provide tensile strength

Severity of disease depends on location of mutation

53
Q

Severity vs gene mutation location in osteogenesis imperfecta

A

Ranges from normal quality collagen but insufficient quantities
To
Mutations encoding middle to C terminal part of protein which is lethal
- e.g. glycine substituted for a bulkier amino acid = collagen fibrils cannot be formed

8 different types

54
Q

Osteogenesis imperfecta symptoms

A
  • Blue whites of the eyes
  • bones fracture easy (due to missing strength)
  • slight spinal curvature
  • loose joints
  • poor muscle tone
  • early loss of hearing in some children
55
Q

Chondrodysplasia mutation and symptoms

A

Mutation in collagen 2 which is needed in cartilage

Symptoms

  • abnormal cartilage, bone and joint deformities
  • shortening of fingers and toes
56
Q

Ehlers-danlo’s syndrome aetiology

A

Mutations in 20 different collagen and collagen related genes

  • collagen 1,2, 5
  • collagen biogenesis/interacting proteins

Leads to abnormal assembly of collagen fibres

57
Q

Ehlers- Danlos syndrome symptoms and complications

A

Symptoms:

  • hyper-flexible joints
  • stretchy skin

Complications:

  • aortic dissection
  • joint dislocations
  • chronic pain
  • early osteoarthritis
58
Q

Elastin related disorders

A

Marian syndrome

59
Q

Marian syndrome symptoms

A
  • tall stature
  • arachnodactyly (excessively long fingers and toes)
  • defects of heart (valves and aorta)
  • chest malformation
  • eye problems (dislocation of lens)
  • flexible joints
  • scoliosis (curvature of the spine)

Death can occur due to rupture of the aorta (thinning of elastin in aorta)

60
Q

Marian Syndrome cause

A

Autosomal dominant (hereditary)

Mutation in FBN1 gene on chromosome 15
- encodes for Fibrillin-1

Fibrillin 1 forms microfibrils which forms a sheath around elastin fibres
- when this is lost elastin is degraded

Molecular Basis Of Disease (17 decks)

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