Lecture 8 - Cells in Tissues 1, Epithelial tissue and cell membrane specialisations

Question 1

What are tissues?

Answer 1

Speicialised, similar cells embedded in an extracellular matrix
Functional arrangement of cells
Form organs, which form organ systems, which form a functional organism
4 key types = epithelial tissue, connective (support) tissue, muscle tissue, nervous tissue

Question 2

4 key types of tissues

Answer 2

epithelial tissue, connective (support) tissue, muscle tissue, nervous tissue

Question 3

Cells

Answer 3

Cells are the building blocks of the body. Cells are embedded within an ECM, adhesion molecules hold cells together and to surfaces (adhesion molecules are contained within the ECM). Cells have an internal cytoskeletal network of filaments for shape, support and movement. Cells secrete proteins and other molecules that make up an ECM which provides support and structure so it can hold cells in place and regulation of cell communication and behaviour

Question 4

ECM is crucial to maintain…

Answer 4

To maintain differentiated state of cells e.g. mouse mammary gland epithelium cultured without ECM are flat and do not produce milk

To maintain normal overall development e.g. inactivating genes for ECM proteins results in defective skeletal development

Question 5

Epithelial tissue - features

Answer 5

Lines organs and cavities within the body

Covers the external body (epidermis)

Protective barrier - both inside and outside of the body

Absorptive and secretory adaptations - individuals epithelial cells within a covering epithelium are very important in excretory products and epithelial cells also come together to form glands which is its secretory adaption

Classified based on layers, shapes, surface specialisations and function

Has polarity (apical and basal surfaces)

Has a basement membrane as a scaffold and anchor to underlying connective (support) tissue

Avascular (nutrients via diffusion) - no blood vessels directly connecting to them and instead they get nutrients through diffusion

Regenerative (stem cells allow regeneration) - highly regenerative so they have high levels of cell turnover compared to other cell and tissue types and stems cells are largely responsible for this regenerative capacity

Question 6

Classification of epithelium based on morphological criteria

Answer 6

Cell shape (squamous, cuboidal, columnar)

Number of cell layers (simple, stratified, pseudo stratified, transitional)

Pseudostratified - effectively are simple because they have one layer however the nuclei are not in an even line, they are actually disordered across the layer which makes them appear stratified

Stratified = multiple layers of cells lying on top of each other like the epidermis

Transitional epithelium is a type of stratified epithelium, not clear how many layers, can contract and expand in order to adapt to the degree of distension needed

Question 7

Cell shapes

Answer 7

Squamous
Cuboidal
Columnar

Question 8

Number of cell layers

Answer 8

Simple
Stratified
Pseudostratified
Transitional

Question 9

Pseudostratified

Answer 9

effectively are simple because they have one layer however the nuclei are not in an even line, they are actually disordered across the layer which makes them appear stratified

Question 10

Stratified

Answer 10

multiple layers of cells lying on top of each other like the epidermis

Question 11

Transitional epithelium

Answer 11

Transitional epithelium is a type of stratified epithelium, not clear how many layers, can contract and expand in order to adapt to the degree of distension needed

Question 12

Classification of epithelium based on surface specialisation

Answer 12

Microvilli

Cilia

Question 13

Classification of epithelium based on whether surface (covering) or glandular (secretory)

Answer 13

Glandular epithelium can be single cells (goblet cells for example) or grouped into glands to allow focused production of a secreted product

Question 14

Epithelial cells are connected via

Answer 14

cellular junctions

Question 15

Occluding junctions

Answer 15

Tight junctions (zonula occludens)

Question 16

Anchoring junctions

Answer 16

Zonula adherens
Desmosomes
Hemidesmosomes

Question 17

Communicating junctions

Answer 17

Gap junctions

Question 18

Tight junctions (zonula occludens)

Answer 18

Tight junctions (zonula occludens) - find these apically between two cells

general function is to prevent leakage of transported solutes and water and seals the paracellular pathway.

Question 19

Zonula adherens

Answer 19

Zonula adherens - anchors cell via the actin cytoskeleton

Question 20

Desmosomes

Answer 20

Desmosomes - anchor epithelial cells to one another

Question 21

Hemidesmosomes

Answer 21

Hemidesmosomes - anchor epithelial cells to the basement membrane

Question 22

Gap junctions

Answer 22

Gap junctions - allows cells to communicate with one another

Question 23

Order of junctions (from basement membrane)

Answer 23

Hemidesmosomes
Desmosomes 
Gap junctions 
Zonula adherens 
TIght junctions

Question 24

Junctional complex

Answer 24

Junctional complex = symmetrical structures formed between adjacent cells and consists of three components- tight junction, zonula adherens, desmosomes

Question 25

Tight junctions location and function

Answer 25

They are at the top/apical surface so they are really controlling the ability of solute molecules to move between our two epithelial cells, selective depending on the tissue type and do allow certain ions and small molecules to move between two epithelial cells on the paracellular pathway therefore selectively permeable Controls paracellular pathway

Question 26

Tight junctions transmembrane proteins

Answer 26

Occludins Claudins Very important component of junction Discovered in 1998 Different Claudins in different tissues allows different molecules to pass between the two epithelial cells

Question 27

Why are claudins important? (tight junctions)

Answer 27

Different Claudins= different permeabilities in different tissues In kidney, only specific regions are permeable to Mg2+ ions due to claudin-16 Mutation in claudin-16 gene = abnormal claudin-16 resulting in junction impermeable to ion Low Mg2+ reabsorption back into the blood Magnesium deficiency Kidney damage/renal failure 200 discovery that claudin-1 responsible for waterproof qualities of skin Mice lacking gene for claudin-1 died at birth due to dehydration

Question 28

Zonula adherens location and function

Answer 28

(below the tight junction) Links cytoskeletons of adjacent cells Actin microfilaments

Question 29

Zonula adherens transmembrane proteins

Answer 29

E-cadherins Each epithelial cell individually produces these e-cadherin proteins and they bind to one another and they pass through the plasma membrane of the cell and it binds to the actin filament via another protein called beta-catenin Band of actin proteins that run around the region of our cells and there are transmembrane proteins that link two cells together via these actin microfilaments

Question 30

Why are cadherins important? (zonula adherens)

Answer 30

Loss of E-cadherins linked to metastasis of cancer cells Malignant cells have lower levels of e-cadherin expression Māori family from the bay of plenty lost 25 members to stomach cancer over a 30 year period 1998 - DNA analysis revealed mutation in gene encoding e-cadherins Now able to be screened and receive preventative surgery

Question 31

Desmosomes (macula adherens) location and function

Answer 31

Links cytoskeletons to adjacent cells Connect to cytokeratin (intermediate filaments) - anchoring to intermediate filaments, you can see on the image that the intermediate filaments are coming together at this electron dense plaque which allows the transmembrane protein to meet with the cytoskeleton and we then have a different set of transmembrane proteins that join together to anchor our two different cells together at a desmosome and these are also cadherins but are different to the ones in the previous junction described

Question 32

Desmosomes transmembrane protein

Answer 32

Cadherins such as desmoglein - important in the functional capacity of the epithelia as seen through disease that attack desmoglein

Question 33

Pemphigus vulgaris

Answer 33

Autoimmune disease Antibodies attack desmoglein 3 which keeps cells bound together Cells fall apart, skin sloughs off Cadherins are important for maintaining structural integrity of epithelium

Question 34

Hemidesmosomes location and function

Answer 34

Anchoring epithelial cell to the basement membrane, one electron dense plaque upon which the intermediate filaments can attach Modified desmosomes Basal surface of cell Bind to cytokeratin which is the same as desmosomes

Question 35

Hemidesmosomes transmembrane proteins

Answer 35

Main transmembrane protein - integrins

Question 36

Gap junctions location and function

Answer 36

Communicating junctions rather than anchoring

Question 37

Gap junctions main transmembrane proteins

Answer 37

Connexins Form channels called connexions that open/cclose Allow passage of ions and small molecules

Question 38

Epithelial tissue is polarised ...

Answer 38

Have an apical and basal surface Linked as sheets through lateral junctions Linked to basement membrane via junctions Different specialisations linked to polarity of cell - provides hints as to function (different specialisations at the apical region compared to the basal region due to polarisation

Question 39

Apical characteristics

Answer 39

Microvilli and cilia

Question 40

Microvilli

Answer 40

Fingerlike projections of plasma membrane Very short ~0.5-1 µm in length Provides increased surface area e.g. for absorption (intestine, kidney) Core of parallel actin bundles Light microscopy = brush border Electron microscopy = individual microvilli with shape maintained by actin filaments

Question 41

Cilia

Answer 41

Non-motile - sensory information, do not have intrinsic movement within them so they are not actually moving, provide sensation of the extracellular environment and conveys it into the cell Motile - beat in rhythm to move substances across surface of epithelium e.g. respiratory tract (mucus and debris moved) Sperm flagellum = modified cilium Up to 10µm long (half cell length) Has cytoskeleton composed of a cord of microtubules (allows a greater range of movement in the cilia)

Question 42

Basal characteristics

Answer 42

Basement membrane | Basal foldings

Question 43

Basement membrane

Answer 43

Binds epithelial cells to connective tissue Basement membrane is extracellular so it is formed and maintained as a consequence of products excreted by both epithelial cells and connective tissue cells and they come together to form a sheet like arrangement of ECM proteins (formed and maintained by both epithelia and connective tissue) Sheet-like arrangement of ECM proteins Forms barrier but allows nutrients to pass to epithelia. Regulates permeability Barrier is important to stop any downward growth of epithelial cells (have a high growth and regenerative capacity) and need this basement membrane to stop the epithelial cells from going into the tissue which ultimately protects from things like cancer Needs to allow nutrients as epithelia is avascular so effectively it is very important in regulating permeability Controls growth and differentiation Under light microscope Not easily distinguished with H&E staining Immunocytochemistry can be used to stain specific components (e.g. collagen IV labelled with immunogold) ``` Under EM three layers are visible Lamina lucida = connected to the epithelial cell, first layer, Lucida because it is lucid in appearance i.e. it comes out light on EM Lamina densa (aka basal lamina) = electron dense region Lamina fibroreticularis = another lucid/electron light region, region that actually connects to the fibres of the connective tissues ```

Question 44

Basal foldings

Answer 44

Increases surface area on basal surface of cell | Can give it striped appearance

Question 45

Functional significance

Answer 45

Acts as protective barrier Junctional complexes - hold epithelium as a sheet For our epithelial cells to work together as a barrier they need to be acting in unison and tightly opposed to one another so our junctional complexes allows out epithelium to work together as a sheet Basement membrane Allows epithelium to stay in one place and be anchored there and not pushed down into the underlying tissue Absorb substance from apical surface and pass on to underlying tissues Microvilli - increasing surface area for exchange, allowing the absorption of more substances Basal foldings Basement membrane

Question 46

Lamina lucida

Answer 46

Lamina lucida = connected to the epithelial cell, first layer, Lucida because it is lucid in appearance i.e. it comes out light on EM

Question 47

Lamina densa (aka basal lamina)

Answer 47

Lamina densa (aka basal lamina) = electron dense region

Question 48

Lamina fibroreticularis

Answer 48

Lamina fibroreticularis = another lucid/electron light region, region that actually connects to the fibres of the connective tissues