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Epithelial Structure Flashcards

1
Q

Xeroderma pigmentosum

A

defect in DNA repair, DNA repaired via nucleotide excision repair

UV sensitivity syndrome (UVSS)

disrupted desmosomes in basal keratinocytes

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2
Q

Connective Tissue

A

directly bears mechanical stresses of tension and compression

bones and tendons

plenty of ECM and sparse cells

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3
Q

Epithelial Tissue

A

polarized

mechanical stresses transmitted from cell to cell by cytoskeletal filaments

cytoskeleton of cells linked from cell to cell by anchoring junctions

ECM is scanty, just thin basal lamina

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4
Q

Cell to cell anchoring junctions

A

adherens junction

desmosomes

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5
Q

Adherens junction

A

cadherins, catenins, and actin
-connect actin bundle from one cell to the next one

-actin-linked cell matrix adhesion anchors actin filament in cell to the ECM

e-cadherins: transmembrane adhesion molecules associated with cell motility and shape

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6
Q

Desmosomes

A

anchoring junctions, attach cells and cytoskeletons to other cells and or to the ECM by using intermediate filaments

found in heart and skin (high stress/tension tissue) because they provide mechanical strength

spot-welds
Ca+ dependent

spot desmosome: between cells
hemidesmosome: bind to ECM

uses cadherins: 1. Desmoglein 2. Desmocollin

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7
Q

Tight junction

A

seals apical membranes, cell polarity is key

gap between epithelial cells
discretion of tight junction

uses 4 pass membrane proteins

  1. Claudin and 2. Occludin
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8
Q

Gap junction

A

creates a pore

allows passage of small water soluble molecules between cells

Connexins: channel forming protein

Couples cells electrically and metabolically (signal transduction and signal depolarization)

important in cell to cell communication

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9
Q

Classical adherins

A

homophilic

e-cadherin

cytoskeleton association: actin filaments via catenins

cell junction association: adherent junctions (cell to cell connection), synapses

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10
Q

Desmosomal adherins

A

homophilic

Desmoglein and Desmocollin

cytoskeleton association: intermediate filaments

cell junction association: desmosomes

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11
Q

Integrins

A

heterophilic

many types

cytoskeleton association: actin filaments,

bind to ECM but not other integrins

cell junction association: focal adhesions (found in hemidesmosomes)

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12
Q

Desmosome mutations

A

Mutation in Desmocollin-2 is associated with arrhythmogenic right ventricular cardiomyopathy (ARVC)

common cause of sudden death in the young

desmosome is not properly inserted in membrane

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13
Q

Blistering Disorders

A

Some autoimmune responses react to desmosome cadherins such as desmoglein 1 and 3

desmoglein 1 in epidermis

desmoglein 3 in spinous layer

desmoglein 1 Attacked by antibodies results in pemphigus foliaceus

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14
Q

Intermediate filaments

A

(think girders in a building)

provide mechanical strength beause they are strong filaments

resist mechanical stresses

keratin

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15
Q

Microtubules

A

(slinky of life)

tube like structures, determine positions of organelles and direct intracellular transport

staggered tetramer of 2 coiled-coil dimers

make up centrioles and mitotic spindles

accessory protein: Tau

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16
Q

Actin filaments

A

determine cell’s surface

necessary for whole-cell locomotion, secretion, and endocytosis

accessory protein: Arp!!!!!!

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17
Q

Fibroblasts

A

make ECM proteins and tissue that epithelial cells sit on

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18
Q

Extracellular Matrix (ECM)

A

secreted by fibroblasts –> provide mechanical support

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19
Q

Blood vessels

A

lined with endothelial cells (polarized)

  • supply nutrients and oxygen
  • remove waste
20
Q

Skin

A

Contains:

  1. ECM
  2. Blood Vessels
  3. Macrophages and dendritic cells
  4. Lymphocytes
  5. nerve fibers
  6. Basal Stem Cell***
21
Q

Basal stem cell

A

responsible for generating tissue in the basal layer
(doesn’t make macrophages)

responsible for integrity of the whole tissue, connected to connective tissues

talks to fibroblasts,

22
Q

Skin layers

A 
Epidermis
– Forms the outer covering of skin
– Creates a water barrier
– Made of epithelial cells
– Continuously repaired and renewed
Dermis
– Second layer
– Rich in collagen
– Provides toughness
Hypodermis
– Fatty subcutaneous layer
    - greatly affected by dehydration-skin turgor
23
Q

Epidermis

A

renewed every 30 days by basal cells (stem cells)

stem cells create 2 cells:

  • one identical cell
  • one cell that differentiates into something specific

changes some desmosomal proteins and some keratins at each layer

24
Q

Epidermis Layers

A

From top down:

  1. keratinized squames, made of keratinocytes
  2. granular cell layer, waterproof barrier
    (also a barrier between inner active layer and outer dead epidermis)
  3. Prickle cell layer
  4. Basal cell layer, attaches to the basal lamina. these are the only dividing cells in the epidermis
25
Stem cell
primitive cell that can self-renew or give rise to more specialized cell types ex: one blood stem cell can give rise to red cells, white cells, and platelets can divide without limit: telomerase Adult stem cells are tissue specific (skin basal stem cells are adult)
26
Transmembrane adhesion proteins
2 families: Cadherins: cell to cell connection Integrins: attachment of cells to matrix
27
Cadherin-Mediated Adhesion
highly selective recognition enable cells of similar types to stick together and segregate from other cells if you lose epithelial cadherin (E-cadherin) you lose the cell to cell connection E to N cadherin switch is important in early development but... E to N switch is mimicked in metastasis later on (breast cancer)
28
Anchor proteins
Beta-catenin, p120-catenin, gamma-catenin
29
Beta Catenin
also a transcription factor when Wnt-1 binds to receptor B-catenin travels to the nucleus from an e-cadhedrin this then begins Wnt1 genes to be expressed (bad) big in cancer signaling
30
B-catenin mutation to cancer
common mutation over expression and cell proliferation inhibits APC (tumor suppressor) RAS is activated (oncogene) other tumor suppressors inhibited including p53
31
Cytoskeleton
important in cell motility guides intracellular traffic includes motor proteins
32
ARP (ARP 2 and ARP 3)
accessory protein to actin important in movement 70 degree angle from mother cell activates formation of actin polymerization and thus cables get built as these cables push forward you get protrusion of membrane and movement of the cell
33
Listeria
presents on surface protein called ActA ActA then activates ARP 2/3 complex causes the toxin to be pushed around on cables and migrates
34
Cell migration by external signals
Rho and Rac are both small G proteins (monomeric, Cdc42 as well) active with GTP and inactive with GDP an external chemoreceptor causes G-alpha-I to inhibit AC and then forces PIP2 to form Rac instead of dissociating this then activates ARP which causes polymerization of actin and thus protrusion (movement of cell) Rho is activated as well and causes contraction (actin-myosin contraction) at the back of the cell to allow continued cell movement
35
Synthetic triterpenoids
drugs that target ARP by inactivating the G-protein good at stopping metastasis also blocking RTK pathway will prevent ARP
36
Integrin downstream signaling
Src/FAK activate ERK and JNK to regulate cell proliferation, cell survival, and differentiation SFK: Src family kinase = activates Grb2 for RTK pathway to get to ERK
37
Laminin
connects many different components together most abundant ECM protein in basement membrane connects cells to ECM components, especially type 4 collagen (network forming collagen) also modulates cell proliferation, differentiation, and motility
38
Collagen
3D shape comes from 3 monomer strands very rich in proline and glycine most common is 1, 2 and 3 types
39
Fibrillar collagen
Types: 1, 2, 3, 5 stabilized by H bond major portion of connective tissue and wound healing strength comes from covalent bonds using lysyl oxidase which requires VIT C** diseases can result: osteogenesis imperfecta Ehlers Danlos syndrome
40
Non-fibrillar collagen
Types 9 and 12 structure of planar basement membranes anchoring fibrils to basement membrane beneath the squamous epithelium
41
Postranslational Hydroxylation
Proline and lysine hydroxylation via: prolyl and lysyl hydroxylases need vitamin c (ascorbic acid) for function of enzymes
42
Ehlers Danlos syndrome
a decrease in lysyl hydroxylase (enzyme) leads to overly flexible joints, blood vessel walls, uterus, Vitamin C needed for this enzyme function
43
Scurvy
loss/deficiency of cofactors Vit C and Fe2+ prolyl hydroxylase affected Sx: wounds reopen, loses teeth, pale skin,
44
Elastin
ability of tissues to recoil and recover shape important in cardiac valves stretching exposes hydrophobic regions, relaxing covers at the core of fibrillin filaments defect in fibrillin leads to Marfan's syndrome, Mitral valve prolapse, and aortic aneurysm
45
Proteoglycan
extracellular molecule made of proteins and sugar fibrous structural protein, binds to protein growth factors heparan sulfate attaches to fibroblast growth factor (FGF) and causes proliferation TGF-beta (transforming growth factor-beta) binds to proteoglycan decorin which inhibits growth factors made of long polypeptides called glycosaminoglycans (GAGs) synthesized by repeating disaccharides, hundreds of sugars in one strand
46
chondroitin 6 sulfate
arthritis, joint relief pharmaceutical treatment
47
Hyaluranon
long repeating sequence of gluconic acid and acetylglucosamine provides mechanical support to tissues attracts a lot of cations (Na+) and draws in water to matrix to help withstand pressure

MCM (6 decks)

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