MCB 11: Assembly of Cells into Tissues II Flashcards
1
Q
How many cell types are there and how do they arise?
A
- there are approximately 200 cell types in humans
- they all arise from one cell due to division and differentiation during development
2
Q
What are the main cell type groups?
Give some examples of cells types in each group
A
- epithelial cells:
- tbc
- connective tissue cells:
- fibroblasts
- chondrocytes (cartilage)
- osteocytes (bone)
- adipose cells
- neural cells:
- neurones
- glial cells (support cells)
- haematopoietic cells:
- blood cells
- cells of bone marrow
- contractile cells:
- skeletal muscle
- cardiac muscle
- smooth muscle
3
Q
Describe the organisation of epithelial cells
A
- they form organised, stable cell-cell junctions
- which form continuous, cohesive layers
- cell-cell junctions are key to the formation and maintenance of epithelial layers
4
Q
What is the function of epithelial cells?
A
- layers of epithelial cells line internal and external surfaces of the body
- they play roles in:
- transport
- absorption
- secretion
- protection
5
Q
What are the two main criteria with which epithelial cells are classified?
A
- Their shape:
- squamous
- columnal
- cuboid - Their layering:
- single layer: simple epithelium
- multi-layer: stratified epithelium
6
Q
Give examples and familiarise yourself with the structure of simple squamous epithelial cells
A
Examples:
- lung alveolar epithelium
- mesothelium: lining of major body cavities
- endothelium: lining blood vessels
- thin epithelium for gas exchange
7
Q
Give examples and familiarise yourself with the structure of simple cuboidal epithelial cells
A
- lining the kidney collecting duct and other ducts
8
Q
Give examples and familiarise yourself with the structure of simple columnar epithelial cells
A
- enterocytes: intestinal absorptive
- many other absorptive and secretory epithelia
9
Q
Give examples and familiarise yourself with the structure of stratified squamous epithelial cells
A
- cells shapes vary throughout the multiple layers, but squamous classification relates to the surface cells
- there are two main types:
1. Keratinizing: e.g. epidermis: nucleus is not visible in surface layer
2. Non-keratinizing: linings of mouth, oesophagus, anus, cervix, vagina (nuclei visible in surface layer cells)
10
Q
Give examples and familiarise yourself with the structure of pseudo-stratified epithelial cells
A
- the surface cells have contact with the basal lamina, despite looking multi-layered
- e.g. ducts in the urinary and reproductive tracts
11
Q
Why must epithelial cells have polarity?
A
- most epithelial functions are directional:
- secretion, fluid and solute transport and absorption do not happen randomly around cells
12
Q
What is key to epithelial polarity?
A
- plasma membrane polarity
13
Q
Describe the two distinct domains of an epithelial cell
A
- The apical domain
- The basolateral domain
- separated by junctions
- both domains have different lipid and protein composition and have unique functions
14
Q
Why is polarisation of secretion key to proper function of epithelial cells?
A
- Directional flow is key for proper function and is achieved by polarity of transporters
- For example digestive enzymes should not be secreted into the basolateral domain by accident as you would digest your own cells.
- watch video in module for more detail
15
Q
How are continuous epithelial layers able to form?
A
- they are able to form because cells make stable cell-cell junctions
- giving epithelia mechanical integrity
- act to seal intracellular pathways of the layer
16
Q
Where are cell-cell junctions found in many epithelia?
A
- found at the apical region of cell-cell contract as a junctional complex
17
Q
What are the two forms of cell-cell junction complexes?
A
- zonulae (belts)
- maculae (spots)
18
Q
What are the four main types of cell-cell junctions in epithelia?
A
- Tight Junctions (Zonulae Occludentes):
- form belt around apical lateral membrane involved in sealing gaps between cells - Adherens Junctions (Zonulae Adhaerentes):
- forms just basally (below) to the tight junctions and controls the assembly of all other junctions. - Desmosomes (Maculae Adhaerentes):
- spot junctions which are scattered throughout the lateral membrane which provide resistance to mechanical stress. - Gap Junctions (Maculae Communicantes):
- clusters of pores which allow exchange of materials and communication between cells to synchronise cellular activities
19
Q
Observe the images of cell-cell junctions in the epithelia
A
20
Q
Describe tight junctions
- location
- proteins of tight junctions
- structure
- main functions
A
- Location:
- typically observed in the apical region of the lateral membranes
- Structure:
- Claudins and Occludin are the major integral membrane proteins of tight junctions (TJ)
- They closely interact with their counterparts on adjacent cells to form sealing strands, usually at the apical lateral region.
- They form a network of contacts, the more elaborate the network, the tighter the seal.
- The cytoplasmic part of the Claudins and Occludin associate with linker proteins that connect them to the actin cytoskeleton
- Functions:
- Gate function
- Sealing effect
- Fence function
- to be explained
21
Q
Describe the gate function of tight junctions
A
- they seal the paracellular pathway (between cells)
- limiting passage of fluids and solutes between cells
- outcomes:
1. Concentration differences across cell layers can be maintained
2. Any solutes crossing the cell layer need to pass through the cells, meaning that the cells can control the passage. - Strong barriers are particularly required when tissues need to transport against a large concentration gradient.
22
Q
Describe the sealing effect of tight junctions
A
23
Q
Describe the fence function of tight junctions
A
- Tight Junctions allow cells to establish and maintain apical-basolateral polarity by preventing the mixing of proteins and lipids between the different plasma membrane compartments.
- In this way, they have a fence function
25
Q
Describe how the structure of adheren junction structure allows continuous belts (zonula) to form
A
- cadherin cell-cell adhesion molecules in AJs bind directly to the same cadherins on adjacent cells (homophilic binding)
- When mature, the junctions form continuous belts (zonula) of adhesion between cells.
26
Q
What are catenins?
A
- Catenins (shown in blues in this diagram) link the cadherins with the actin cytoskeleton, and control the junctional dynamics
27
Q
What does this image describe?
A
- When epithelial cells initially make contact, the junctions are small, but the formation of more protrusions and contacts leads to recruitment of more adhesion molecules and their cytoplasmic binding partners
- regarding adherens junctions
28
Q
What is the role of adherens junctions (cadherin-mediated adhesion belts) in the formation of epithelial tubes?
A
- Adherens junctions (cadherin-mediated adhesion belts) are associated with circumferential actin bundles that contain myosin, and can contract.
- This controlled contraction can lead to epithelial tube formation as seen in the diagram on the right.
29
Q
Describe desmosomes
- associations with other structures
- function
A
- Desmosomes are associated with the intermediate filaments of the cytoskeleton, cytokeratins in epithelia,
- which mechanically link cells to each other and to the ECM (via hemidesmosomes)
- This arrangement provides mechanical stability to tissues including epithelia and cardiac muscle.
- Desmosomes are abundant between the cells of stratified squamous epithelia
- If desmosome function is compromised, these epithelia become fragile and easily damaged
- made of desmosmal cadherins
30
Q
Describe gap junctions
- structure
- function
A
- made up of clusters of pores formed from 6 identical subunits in the membrane
- these pores are continuous with pores in adjacent cell membrane
- these junctions allow the passage of ions and small molecules between cells.
- pH, Ca2+ concentration, voltage and some signalling molecules can control passage, i.e. can open and close pores thereby controlling cell-cell communication.
- Gap junctions are also known as the electrical synapse:
- they are important in the passage of electrical signals, using the flow of ions, in some tissues (e.g. cardiac muscle)
31
Q
Describe the structure of gap junction channels
A
- they are called connexons made up of connexins
- Individual transmembrane connexins assemble to form 6-subunit channels called connexons
- these channels link to others on adjacent cells to form gap junction channels
32
Q
Describe how gap junction channels are able to restrict the size of solute that pas through
A
- Inorganic ions and small water-soluble molecules, but not macromolecules, can pass between cells through gap junction channels.
- The channels are not always open
- They can be opened or closed by signalling molecules and some ions.
- The diagram below illustrates the restrictive properties of gap junction channels.
- Solutes of molecular mass greater than 1000 are not able to pass through to an adjacent cell.
35
Q
What does this micrograph show in terms of epithelial function?
A
36
Q
Describe transporting epithelia
- characteristics
A
- In transporting epithelia, the plasma membranes contain high concentrations of ion transporters
- Typically, mitochondria are closely associated with extensive basal membrane infoldings, providing energy for active transport across the abundant membranes
- The infoldings increase the amount of basal membrane available to house the active transporters that can pump ions and water.
37
Q
Describe absorptive epithelia
A
- Maximising the efficiency of absorption can involve increasing the surface areas of absorbing tissue, and increasing the surface area of the plasma membrane that carries the specific membrane transporters
- A clear example of where this happens is in the small intestine, which absorbs digested nutrients
- The small intestine surface area is increased by the fact that it is long, and by the interior surface of the wall of the small intestine being folded into numerous finger-like processes that point into the interior: the villi (singular, villus). The villi are covered with intestinal epithelial cells
- Carriers transporting nutrients are found on the microvillous brush-border membranes, e.g. absorptive intestinal cells (enterocytes) and kidney proximal tubule cells
38
Q
What kind of secretory cells do the pancrease have>
A
- exocrine (into the duct or lumen)
- endocrine (into the bloodstream)
39
Q
Describe secretory epithelial cells (exocrine)
use diagrams to help
A
- As you can see, the cells have abundant RER in the basal region, and numerous secretory vesicles in the apical cytoplasm
40
Q
Describe secretory epithelial cells (endocrine)
A
The diagram below shows the typical organisation of an endocrine secretory cell (endocrine = secretes into the bloodstream).
- As you can see, endocrine cells secrete their contents to the basal aspect.
- In the image on the right below, you can see that a thin-walled capillary is surrounded by the basal aspects of endocrine secretory cells.
- The secretory vesicles are positioned so that when their contents are released, they have close access to the blood circulation
41
Q
How are secretory epithelial arranged?
A
- epithelium is often arranged in tubules and glands of varying complexity
- see image
43
Q
Describe protective epithelial
- type of cell
- forms
- function
A
- protective epithelia are usually stratified-squamous
- two types:
- keratanising
- non-keratinising
- This type of epithelium can form thick layers that protect underlying tissues from various physical, biological, and chemical insults, e.g. heat, cold, solvents (alcohol), abrasion, etc.
44
Q
Look at these diagrams and compare keratinizing and non-keratinising stratified squamous epithelia
left: keratinizing
right: non-keratinizing
A
45
Q
How is cervical cancer detected?
A
- through a pap smear where surface cells of non-keratinising stratified squamous epithelium of the uterine cervix are sampled
49
Q
What is the cell turnover of these epithelial tissues
- small intestinal
- colon epithelial
- epidermis
A
50
Q
Describe the turnover of intestinal villi and glands
A
- The small intestine and colon have glands, extending into the wall of the gut, which have important roles in epithelial-turnover.
- Stem cells in the crypt divide to form transit amplifying cells, which proliferate rapidly, moving up walls of the crypt.
- They differentiate into goblet cells and enterocytes, whilst moving up the wall of the villus.
- At the tip of the villus, they undergo apoptosis and are shed into the lumen.
- This mechanism prevents colon cancer as accidentally mutated epithelial cells are shed within days of their formation.
- Adenomas in the crypt are formed when functional APC (Adenomatous polyposis coli) protein is absent, leading to the accumulation of transit amplifying cells.
- This occurs because beta-catenin cannot be inactivated, so accumulated in transit amplifying cells, blocking their out-migration and differentiation.
- The adenoma becomes a carcinoma when further mutations accumulate in the mass of transit amplifying cells, causing such a change.
51
Q
What does treating mice with the cancer chemo drug 5-FU do to the small intestinal villi?
A
- The drug slows down or stops cell division in the crypts.
- Cell loss from the villus tips continues as normal, but the failure to produce new cells to replace the lost cells results in a loss of tissue and the villi shorten.
- This is a major reason why chemotherapy can have strong side-effects on the gut.
52
Q
What happens when there is increased cell proliferation?
A
- When there is too much cell proliferation, the rate of cell loss is not sufficient to maintain the normal tissue volume.
- In the colon, if a cell mutates such that its proliferation is dysregulated, too much tissue is formed.
- This is a benign tumour called an adenoma, also called a polyp.
- Although not malignant, these adenomas have a high risk of acquiring more mutations that switch it to being malignant (i.e. cancer).
53
Q
Describe cell turnover in the epidermis
A
- As the diagram on the right shows, surface cells are constantly being lost, but are replaced by new cells being formed in the basal layer which migrate up while undergoing a programme of differentiation that eventually leads to them flattening out and keratinising.
- Each layer replaces the one above as the layers are lost from the surface.
54
Q
What causes a callus?
A
- you are applying pressure and abrasion to areas of the skin.
- This stimulates the stem cells in the basal layer of the epidermis in that area to divide more rapidly, and the rate of loss from the surface is less than the rate of new cell production,
- so there is an increase in tissue mass to offer greater protection to the area being pressured.
- the increase in pressure resulting from new, or greater, activity in an area of skin, stimulates increased cell production in the epidermis basal layer.
- This increase in cell production is greater than the cell loss from the surface, so cells accumulate causing the increased thick hard layer: the corn or callus.
55
Q
What infection agents can affect the turnover of the epidermis?
Both increase and decrrease
A
- Warts are the result of infection of the epidermal keratinocytes by one of the family of human papilloma viruses (HPV). The virus hijacks the cell’s proliferation machinery and increases the rate of cell proliferation.
- The epidermis can also be affected by a reduction in cell division. Many chemotherapeutic drugs that target cell division of tumour cells will also prevent cell proliferation in epidermis, leading to a number of possible skin problems as well as affecting hair and nails.
- Did you know? Hair loss during chemotherapy happens because cell production in the hair follicles is reduced, and they can’t produce new cells fast enough.
56
Q
Give examples of some normal physiological examples of changes in cell-turnover rate
A
