Pathology 2: the cell in health and disease

Question 1

Define homeostasis and give an example of a negative feedback loop and a positive feedback loop.

Answer 1

• Homeostasis = the process by which internal variables are kept within a normal range of values
• eg. of a negative feedback loop = the control of blood sugar by insulin
• eg. of a positive feedback loop is the coagulation (clotting) cascade

Question 2

List the main functions of mitochondria

Answer 2

1. Generation of ATP (oxidative phosphorylation).
2. Source of molecules used to create proteins, nucleic acids and lipids (intermediate metabolism).
3. Regulation of apoptosis (programmed cell death).
4. Source of reactive oxygen species.
5. Production of haem (for haemoglobin).
6. Generation of heat.

Question 3

What is the function of lysosomes?

Answer 3

• Lysosomes are membrane-bound organelles that contain enzymes capable of breaking down proteins, nucleic acids, carbohydrates and lipids
• they function as the digestive system of the cell degrading material taken up from outside the cell and digesting obsolete components of the cell itself

Question 4

What is the function of the Golgi apparatus?

Answer 4

• protein modifications and for glycosylation of proteins and lipids

Question 5

What is the function of the Rough Endoplasmic Reticulum (RER)?

Answer 5

• Production of proteins and lipids and production of all of the cell organelles
• Ribosomes translate mRNA into proteins and these proteins fold in the endoplasmic reticulum
• sugars can also be added to proteins in the RER
• note: if proteins misfold they are degraded or if this is excessive a stress response is triggered which can then initiate apoptosis

Question 6

What is the function of the Smooth Endoplasmic Reticulum (or sarcoplasmic reticulum)?

Answer 6

• Site of steroid and lipoprotein synthesis
• it can also make drugs less hydrophobic allowing their export
• release and storage of calcium ions that regulate muscle contraction

Question 7

List 4 components of the cytoskeleton

Answer 7

1. Actin microfilaments
2. Microtubules
3. Nuclear membrane lamins
4. Intermediate filaments eg. cytokeratin

Question 8

In cell membranes, phosphatidylserine normally faces inwards. What happens if this molecule flips to face outwards?

Answer 8

• It becomes an ‘eat me’ signal for phagocytes (a cell which can gobble other cells or particles), in the setting of apoptosis (programmed cell death).

Question 9

List the 6 ways in which molecules can move across membranes and give one example of a substance which uses each method.

Answer 9

1. Passive diffusion eg. oxygen.
2. Fast channel proteins (using concentration gradients) eg. sodium.
3. Slow carrier proteins eg. amino acids.
4. Endocytosis (receptor or caveolae mediated) eg. LDL (receptor-mediated) and folate (caveolae-mediated).
5. Phagocytosis eg. bacteria.
6. Trancytosis eg. antibodies from breast milk passing through intestinal cells into baby.

Question 10

Which ion channel is damaged in the disease cystic fibrosis?

Answer 10

• The cystic fibrosis transmembrane regulator or CFTR, which is responsible for chloride transport across cell membranes
• this leads to the secretion of sticky thick mucus

Question 11

List four mechanisms by which cells communicate.

Answer 11

1. Autocrine signalling
2. Paracrine signalling
3. Endocrine signalling
4. Synaptic signalling

Question 12

List 4 possible outcomes following a ligand binding to a cell surface receptor and give one example of a ligand associated with each outcome.

Answer 12

1. An ion channel opens eg. neurotransmitter at neuromuscular junction.
2. A G-protein is activated eg. hormones.
3. A tyrosine kinase is activated eg. epidermal growth factor.
4. A latent transcription factor is activated eg. interferon.

Question 13

Describe the function of a transcription factor and give one example of a transcription factor which facilitates cell division and one which stops cell division.

Answer 13

• Transcription factor = a protein which controls the rate of transcription of genetic information from DNA to messenger RNA by binding to a specific DNA sequence.
• note: MYC is an example of a TF that facilitates cell division and p53 is an example of one which stops division.

Question 14

List 5 functions of growth factors.

Answer 14

1. Stimulate activity of proteins needed for cell survival, growth and division.
2. Promote entry of cells into the cell cycle.
3. Relieve blocks on cell cycle progression.
4. Prevent apoptosis.
5. Enhance synthesis of cell components.

Question 15

List 4 functions of the extracellular matrix.

Answer 15

1. Anchors cells (maintains their polarity and supports cell migration).
2. Controls cell proliferation.
3. Provides a scaffold for tissue repair/regeneration.
4. Creates tissue microenvironments.

Question 16

What structural feature of collagen gives it strength and which vitamin is needed for collagen production? Give an example of one disease caused by a genetic collagen defect.

Answer 16

• Collagen has a triple helical structure which gives it significant strength
• strength increased by presence of lateral cross links of the triple helices by covalent bonds which require vitamin C to form
• note: genetic defects in collagen result in diseases such as osteogenesis imperfecta and Ehlers-Danlos syndrome

Question 17

Which disease is caused by a mutation in a component of elastin and what are the clinical consequences of abnormal elastin in this disease?

Answer 17

• Marfan’s syndrome is caused by a mutation in the fibrillin-1 gene which is a component of elastin and elastin is important in the structure of heart valves, blood vessels, skin and ligaments
• heart defects and lens dislocations are seen in Marfan’s syndrome

Question 18

What are integrins and give two examples of where integrins are important in biology?

Answer 18

• Integrins are transmembrane glycoproteins which attach cells to the extracellular matrix and mediate cell-cell interaction. Integrins mediate the interaction between white blood cells and the lining of blood vessels in the setting of inflammation.
• They are also important in platelet aggregation in clotting and in tumour invasion.

Question 19

What drives cell cycle progression?

Answer 19

• Driven by proteins called cyclins and cyclin-associated enzymes called cyclin-dependent kinases (CDKs)

Question 20

Where are the checkpoints in the cell cycle and what happens at each checkpoint?

Answer 20

• Start (G1/S) checkpoint - to check if nutrition, the environment and cell size are favourable for replication and that all DNA is intact
• G2/M checkpoint - to check that DNA has been completely replicated
• Metaphase/anaphase checkpoint - to check that all DNA is intact and if all chromosomes are attached to the mitotic spindle

Question 21

What enforces cell cycle checkpoints and give an example of one of these? What is the consequence of a defective cell cycle enforcer?

Answer 21

• Cyclin-dependent kinase inhibitors (CDKIs) stop the cell cycle and enforce the checkpoints (eg of a CDKI. p16)
• defective CDKI checkpoint proteins allow cells with DNA damage to replicate increasing the risk of malignancy

Question 22

What is the difference between embryonic stem cells and adult stem cells?

Answer 22

• Embryonic stem cells = totipotent stem cells which can give rise to all types of differentiated tissues
• Adult stem cells (also known as tissue stem cells) can only replace cells in the tissue in which they reside and these cells are found in stem cell niches in many organs

Question 23

What are the two properties which define a stem cell?

Answer 23

1. Self-renewal - the capacity of stem cells to retain their numbers.
2. Asymmetric division - the capacity of stem cells to generate two daughter cells, one of which can differentiate into mature cells and one of which remains undifferentiated and retains its self-renewal capacity.

Question 24

Mitogen-Ativated-Protein (MAP) kinase pathway…

Answer 24

• This pathway is switched on in many cancers
• The signalling molecule binds to receptor tyrosine kinase (RTK) molecule which causes the cell to divide

Question 25

What is the main structural protein of the extra-cellular matrix, and what protein allows the extra-cellular matrix elastic

Answer 25

• Collagen (needs vit C to keep strength)
• Elastin (made up of a protein called fibrillin)