Cell proliferation and death, cytokines and signalling

Question 1

Apoptosis

Answer 1

Programmed cell death

Question 2

Necrosis

Answer 2

lethal cell injury or accidental cell death

Question 3

Characteristics of apoptosis

Answer 3

• Can be a physiological or pathological process
• Membrane integrity is maintained
• Cell shrinkage occurs
• There are characteristic nuclear changes e.g. DNA cleavage
• Formation of apoptotic bodies
• Activation of specific caspace proteases

Question 4

Characteristics of necrosis

Answer 4

• Always a pathological process
• Membrane integrity is lost
• Cell swelling occurs
• Loss of cell nuclei
• Leakage of lysosomal enzymes

Question 5

Mutagenesis

Answer 5

The production of genetic mutations

Question 6

Oncogenesis

Answer 6

The development of a tumour

Question 7

Neoplasia

Answer 7

abnormal proliferation of cells

Question 8

Characteristics of benign tumours

Answer 8

• No metastasis
• Good demarcation from surrounding tissues
• Well differentiated mass
• Low mitotic rate
• Minimal nuclear or cell pleomorphism

Question 9

Characteristics of malignant tumours

Answer 9

• Frequent metastasis
• Invades surrounding tissues, blood and lymphatic vessels
• Disorganisation of tissue
• High mitotic rate
• Increased nuclear or cell pleomorphism

Question 10

Why is cell signalling important?

Answer 10

Required for:

• Movement
• Growth
• Metabolism
• Development
• Immune response

Question 11

How is signal specificity achieved?

Answer 11

• Sometimes cell-to-cell contact is required
• Sometimes specific receptors are required; only certain cells/under certain conditions will express the protein for a receptor

Question 12

Autocrine

Answer 12

self-signalling; direct feedback on the cell that provduced the signal.

Question 13

Paracrine

Answer 13

the signal has an effect on a cell nearby.

Question 14

Endocrine

Answer 14

the effect is on a distant cell. The signalling molecules travel in the bloodstream.

Question 15

Cytokines

Answer 15

soluble proteins or glycoproteins produced by cells. Important signalling molecules, esp. in inflammation and innate immunity.

Question 16

What does pleiotrophy refer to?

Answer 16

the property of a single cytokine to be able to have different effects on different cells.

Question 17

Describe cell signalling by gap junctions

Answer 17

• Cells communicate via cytoplasmic bridges
• This allows signalling molcules to pass between cells without being secreted into extracellular fluid
• Contact-dependent

Question 18

Pros and cons of signalling via gap junction

Answer 18

✅Can efficiently move ions, metabolites, intracellular signalling molecules

❌ Can only communicate with adjacent cells

❌ Relatively slow transmission if across a large tissue area

❌ Potential for transmission of deleterious factors from one cell to another

Question 19

Describe cell signalling by synaptic transmission

Answer 19

Communication between neurones involves chemical messenger across short synaptic cleft.

Question 20

Pros and cons of cell signalling by synaptic transmission

Answer 20

✅ System can be activated very quickly

❌ Hardwiring is expensive - requires much energy to build and maintain

❌ Possibly vulnerable - if damaged, is hard to repair

Question 21

Describe receptor-mediated signalling

Answer 21

• Sometimes cell-to-cell contact is required, however sometimes long-distance communication is possible

Question 22

Pros and cons of receptor mediated signalling

Answer 22

✅ Can signal over long distances

✅ Signal specificity can be achieved

❌ May take time to elicit a response

Question 23

What type of cell signalling is shown here?

Answer 23

Autocrine

Question 24

What type of signalling is shown here?

Answer 24

Paracrine

Question 25

What type of signalling is shown here?

Answer 25

Endocrine

Question 26

What property of cytokines is shown here?

Answer 26

Pleiotrophy

Question 27

What property of cytokines is shown here?

Answer 27

**Redundancy**: two or more cytokines may have the same/similar effect.

Question 28

What are the effects of inflammation?

Answer 28

* Rubor * Calor (heat) * Swelling * Pain (dolor) * Loss/lack of function

Question 29

Acute inflammation

Answer 29

normal response to most forms of injury/infection. Subsides once the infection is removed.

Question 30

Chronic inflammation

Answer 30

initially, the normal response to most forms of injur/infection, but the wound does not heal (due to the perisistence of a foreign body/continuing infection)

Question 31

Inflammatory response

Answer 31

an innate immune response that ensures immune cells and other substances are brought to the area so that: * foreign organisms may be destroyed/inactivated * injured tissues/cells may be removed * favourable conditions for the healing process are provided

Question 32

Describe the process of acute inflammation

Answer 32

1. infection/tissue damage or injury stimulates cytokine production by the eptihelium 2. Cytokine production stimulates other resident cells and attracts mast cells 3. Histamine (e.g. as secreted by mast cells) as well as other vasoactive substances increase vascular permeability 4. Chemokines attract neutrophils and monocytes which migrate out of the blood vessel 5. Acute phase reactants (a.k.a. APPs) are present in the blood serum. They are important mediators of the inflammatory process.

Question 33

What are the first cells at the site of inflammation (after mast cells)?

Answer 33

Neutrophils

Question 34

Describe the inflammatory cascade

Answer 34

* Inflammatory cells infiltrate, producing cytokines and chemokines * More resident cells become activate, more cells extravasate * Amplification of the immune response leads to clearing of the antigen

Question 35

What are the effects of histamines?

Answer 35

* Dilation of blood vessels * Increase permeability of blood vessels * Activation of the endothelium, changing its properties * --\> Leads to warmth, redness, local oedema and attraction of other inflammatory cells to the site of infection * Irritation of local nerve endings leading to itching and pain

Question 36

What is diapedesis?

Answer 36

The process by which leucocytes reorganise their cytoskeletons to move between gaps in the endothelium and pass into the tissue.

Question 37

Outline the effects of inflammation on local vasculature

Answer 37

* Blood vessel endothelium local to the area of inflammation expresses new receptors called selectins * External signals cause certain leucocytes to also express integrins which can bind to the new receptors * Binding of integrins with their receptors slows down leucocytes near the site of infection ("tethering and rolling") * Immbolised leucocytes undergo diapedesis and migrate along chemokine gradients into tissues

Question 38

What are acute phase proteins and where are they produced?

Answer 38

* APPs: plasma proteins made in the liver in response to cytokines secreted during inflammation. * e.g. C-reactive protein in response to IL-6 * They can serve as markers for systemic inflammation

Question 39

What is a granuloma and how is it formed?

Answer 39

* Granuloma formation can be the response to chronic inflammation * Involves containment of the a stimulus that has failed to be neutralised. However, it can reduce organ function 1. Macrophages receive persistent stimulation 2. Summon more macrophages 3. Chronically stimulated inflammatory cells aggregate; there is a collection of modified macrophages (=epitheliod cells) and a surrounding zone of lymphocytes