Cell Adhesion I - Keeping cells together Flashcards
What is the main stress bearing component of epithelial tissue?
Cell cytoskeletons
Cell-cell and cell-matrix junctions
What is the main stress bearing component of connective tissue?
Extracellular matrix
What is epithelial tissue?
Tissue that lines body surfaces, cavities and tubes
Supported by an underlying basement membrane
What type of junctions are contained within epithelial tissue?
Desomsomes
Hemidesomosomes
How is epithelial tissue classified?
- Number of cell layers - Simple, Pseudostratefied, stratified
- Cell shape - Squamous, Cuboidal, columnar
- Presence of surface specialisations - Keratinisation, microvilli
What are the distinguishing features of epithelial cells?
Apical surface is free
Basal surface is attached to BM
Lateral surfaces adhere to neighbouring cells
Polarised morphology
Presence of specialised cell-cell junctions
What are the various cell-cell and cell-matrix junctions?
Tight junctions - Boundary between apical and basal domain
Cell-cell:
Adherens junctions
Desmosomes
Cell-matrix:
Hemidesmosomes
Focal adhesions
What do cell-cell junctions do?
Rivet cells together
What do cell-matrix junctions do?
Rivet the cells to the basement membrane
What is the cell-cell and cell-matrix junctions important for?
Maintaining tissue integrity
What are the components of the cytoskeleton?
Actin microfilaments - cell migration
Microtubules - Cell division
Intermediate filaments - maintaining tissue integrity
What are the 3 major types of intermediate proteins and what cell types are they found on?
Keratin - Epithelial cells
Vimentin - Mesenchymal cells
Desmin - Myocardial cells
What are keratin intermediate filaments?
Assemble into heterodimers of type 1 (acidic) and type 2 (basic) keratins
Keratin IFs associate with desmosomes in epithelial cells
What is the structure of the skin?
Epidermis - stratified keratinised epithelium
Dermis - dense fibroelastic connective tissue
Hypodermis - Loose fibro-fatty connective tissue
What are some epidermal appendages?
Hair follicles
Sebaceous glands
Sweat glands
What are the layers of the epidermis?
4 layers: Stratum corneum Granular Spinus Basal
What are the cell types found in the epidermis?
Keratinocytes (>90%)
Mealnocytes
Langerhans cells
What is the purpose of the epidermis?
Prevents microbial invasion and loss of water (barrier function)
Essential for survival
What are desmosomes?
Mediate cell-cell adhesion
Anchor keratin intermediate filaments into the membrane
What are desmosomes made up of?
Desmocollins & Desmogleins - Membrane spanning proteins
Plakoglobin & Plakophilin - Cytoplasmic proteins
Desmophakin - links structure to cytoskeleton
What are the desmosomal cadherin families?
Desmocollins - DSC1, DSC2, DSC3
Desmogleins - DSG1, DSG2, DSG3, DSG4
(all 7 act in the epidermis)
What desmosomal cadherin family act in the upper layers of the epidermis?
DSC1 and DSG1
What desmosomal cadherin family act in the lower layers of the epidermis?
DSG3 and DSC3
What is pemphigus?
An autoimmune (acquired) blistering disease caused by defective cell-cell adhesion
What are the 2 types of pemphigus?
Pemphigus foliaceus
Pemphigus Vulgaris
What is Pemphigus foliaceus?
Autoantibodies targeting DSG1 (upper epidermis) causing blistering in the upper epidermis.
Good prognosis
What is Pemphigus Vulgaris?
Autoantibodies target DSG3 (lower epidermis)
Blistering in lower epidermis
epidermis is severely compromised
poor prognosis
Almost always fatal if untreated due to fluid loss and infection
Where are hemisdesmosomes found?
Mediate cell-matrix adhesion
found at the basal surface of the basal layer cells
What do hemidesmosomes do?
Interact with keratin IFs anchoring them to the basement membrane in the cell
Also interact with laminin-5 out of the cell
What is the basement membrane?
Underlies all epithelial tissue
Not vascularised
What are the components of the basement membrane?
Laminin
Collagen IV
What is laminin?
Consist of 3 chains (alpha, beta, gamma) arranged in an asymmetric cross
Contain collagen and cell binding domains
What does laminin do?
Contributes to organising the matrix and helping cells attach to it
What is collagen?
Most abundant protein in mammals
Found in the BM and connective tissue
What is the structure of collagen?
3 alpha chains forming a triple helical structure
Helices form fibrils
Fibrils form collagen fibres
What is the hemidesmosome composition?
Alpha 6 beta 4 integrin
BPAG1/2 (bullous pemphigoid antigen 1/2)
Plectin
What is epidermolysis bullosa?
A family of genetic (inherited) blistering diseases of the skin caused by defective cell-ECM adhesion
What are the 3 types of EB?
EB simplex
Junctional EB
Dystrophic EB
What is EB simplex?
Tissue separation of the epidermis (basal)
Generally localised to hands and feet
Mutation in keratin 5, BPAG1, a6b4 integrin
What is Junctional EB?
Tissue separation of the basement membrane
Patients have large areas of body devoid of skin due to blistering
Mutation in Laminin5, BPAG2, a6b4
What is Dystrophic EB?
Tissue separation in upper epidermis
Repeated blistering and scarring throughout life. Join contractures and fusion of digits
Mutation in Collagen VII
