Cell adhesion Flashcards

1
Q

What are the main components of epithelial cells and connective tissue?

A

Mechanical properties of epithelial cells are mediated by cytoskeletal filaments - anchor cells to each other and to surroundings. Helps with mechanical force and tension and can transfer to the matrix.
For connective tissue, the ECM directly bears the mechanical stress of tension and compression.

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2
Q

What are epithelial tissues?

A

e.g. epidermis
Composed of tightly packed sheets of cells.

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3
Q

What are characteristics of epithelia?

A

Line body surfaces, cavities and tubes.
Supported by connective tissue and basement membrane - not penetrated by blood vessels.
So epithelial tissues get nutrients by diffusion through the membrane.

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4
Q

How are epithelia classified?

A

Number of cells: simple, pseudostratified, stratified.
Shape of cells: Squamous, cuboidal, columnar.
Surface specialisations: Keratinisation, microvilli

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5
Q

What are the surfaces of epithelial cells?

A

Apical surface is the top and faces the lumen.
The Basal surface is attached to the basement membrane.
Lateral surfaces adhere to those of neighbouring cells.

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6
Q

What are tight junctions?

A

Defines the boundary between the Apical and Basolateral domains.
Has polarised morphology - knows which side of the cell is which.

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7
Q

What is the barrier function of tight junctions?

A

Barrier function - prevent macromolecules diffusing between cells.

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8
Q

What is the fence function of tight junctions?

A

Fence function - prevent proteins from the Apical domain diffusing into the Basolateral domain.

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9
Q

What are cell junctions?

A

Tight junction
Adherens junction
Desmosome, these 3 are cell:cell adhesion.
Gap junctions.
Hemidesmosome and focal adhesion are cell:matrix junctions

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10
Q

What are filaments used by the cell junctions?

A

Actin microfilaments are used by tight and adherens junctions, and focal adhesions.
Keratin intermediate filaments are used by hemidesmosomes and desmosomes.

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11
Q

What are the functions of the cell junctions?

A

Apical: Tight junctions - barrier and fence
Adherens junctions - cell to cell adhesion
Desmosomes - cell to cell adhesion
Basal: Gap junction - communications
Hemidesmosomes - cell to matrix adhesion
Focal adhesions - cell to matrix adhesion

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12
Q

What is the cytoskeleton?

A

Extends through the cytoplasm.
Consists of microfilaments, microtubules and intermediate filaments.

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13
Q

What is the cytoskeleton important for?

A

Cell migration (microfilaments)
Cell division (microtubules)
Maintaining tissue integrity (intermediate filaments)

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14
Q

What are the types of intermediate filaments?

A

Keratin, in epithelial cells - heterodimer, 40+ genes.
Vimentin, in mesenchymal e.g. fibroblasts - homodimer.
Desmin, in myocardial - homodimer.

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15
Q

What are keratin intermediate filaments?

A

Keratin IFs associate with desmosomes.
Assembled from dimers of type I (acidic) and type II (basic) keratin.

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16
Q

What are the structures of the skin?

A

Epidermis - stratified, squamous, keratinised epithelium.
Dermis - dense fibro-elastic connective tissue - collagen and elastin.
Hypodermis - loose, fibro-fatty connective tissue - fat cells.
Epidermal appendages - hair follices, sebaceous glands, sweat glands.

17
Q

What is the epidermis?

A

Mainly Keratinocytes
Also melanocytes and Langerman’s cells.
Prevents microbial invasion and loss of water.

18
Q

How do keratinocytes evolve through the epidermis?

A

Keratinocyte stem cells in the basal membrane divide to produce more, then detach from the basement membrane and migrate up through the layers of the epidermis.
They differentiate and lose their nuclei, flatten out, secrete lipids, and then are eventually lost from the skin.

19
Q

Which keratinocytes genes are expressed in the epidermis?

A

In the basal layer, K5 and K14 genes are expressed.
As they differentiate and move up the layers, the gene expression switches to K1 and K10.

20
Q

What are desmosomes?

A

Mediate cell:cell adhesion.
Anchor keratin IF to the membrane.
Anchor cells together.
Found also in meninges of brain, and heart muscle.

21
Q

What is the composition of desmosomes?

A

Desmosomal cadherins - demacollins and demogleins.
Plakoglobin.
Plakophilin.
Desmoplakin.

22
Q

What are desmosomal cadherins?

A

Desmocollins - DSC1, DSC2, DSC3
Desmogleins - DSG1, DSG2, DSG3, DSG4
Single pass transmembrane proteins.
Intracellular domains interact with plakoglobin and plakophilin.

23
Q

How is gene expression of desmosomal cadherins changed?

A

DSG3 and DSC3 are higher in the structure.
DSG1 and DSC1 are lower in the basement membrane.

24
Q

What is Pemphigus?

A

Autoimmune disease caused by defective cell:cell adhesion.
Pemphigus foliaceus, caused by pathogenic autoantibody which recognises DSG1.
Pemphigus Vulgaris, caused by pathogenic autoantibody which recognises DSG3.

25
Q

How does Pemphigus happen?

A

Antibodies get between the cells in the epidermis and bind their antigens.
This prevents the interaction of desmosomal cadherins from neighbouring cells.
This causes the keratinocytes to pull apart and cause skin blistering.

26
Q

How does the prognosis of Pemphigus change?

A

For pemphigus foliaceus, occurs in upper epidermis, so largely intact, prognosis good.
For pemphigus vulgaris, occurs in lower epidermis, epidermis severely compromised and prognosis is poor - fatal.

27
Q

What are hemidesmosomes?

A

Mediate cell:ECM adhesion.
Found in simple and stratified epithelia at basal surface.
Anchor keratin IF to membrane.
Extracellularly, interact with ECM components - laminin-5, collagen VII.

28
Q

What is laminin?

A

Component of basement membrane.
Consists of a,b and d chains arranged in an asymmetrical cross.
Contains collagen and cell-binding domains.
Helps epithelial cells attach to basement membrane.

29
Q

What is collagen?

A

Synthesised by fibroblasts.
Found in basement membrane, connective tissue and bone.
3 collagen a-chains are wound round each other to form a triple helical structure, then assemble into fibrils, which aggregate into large fibres.
Resist stretching forces on connective tissues.

30
Q

What are the components of hemidesmosomes?

A

BPAG1
Plectin, these two in cytoplasmic space.
BPAG2, transmembrane protein, links the molecules across membrane to laminin.
Integrin

31
Q

What is Epidermolysis Bullosa?

A

EB is a genetic blistering disease caused by defective cell-ECM adhesion (hemidesmosomes).
EB simplex
Junctional EB
Dystrophic EB

32
Q

What is EB simplex?

A

Tissue separation at epidermis.
Mutation of keratin 5 and 14, BPAG 1 and plectin.
Mild prognosis

33
Q

What is junctional EB?

A

Tissue separation at basal membrane
Mutation of laminin 5 and BPAG2.
Severe prognosis.

34
Q

What is dystrophic EB?

A

Tissue separation at upper dermis.
Mutation of collagen VII.
Severe prognosis, though slightly less than junctional