Cell proliferation and death, cytokines and signalling Flashcards
Apoptosis
Programmed cell death
Necrosis
lethal cell injury or accidental cell death
Characteristics of apoptosis
- 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
Characteristics of necrosis
- Always a pathological process
- Membrane integrity is lost
- Cell swelling occurs
- Loss of cell nuclei
- Leakage of lysosomal enzymes
Mutagenesis
The production of genetic mutations
Oncogenesis
The development of a tumour
Neoplasia
abnormal proliferation of cells
Characteristics of benign tumours
- No metastasis
- Good demarcation from surrounding tissues
- Well differentiated mass
- Low mitotic rate
- Minimal nuclear or cell pleomorphism
Characteristics of malignant tumours
- Frequent metastasis
- Invades surrounding tissues, blood and lymphatic vessels
- Disorganisation of tissue
- High mitotic rate
- Increased nuclear or cell pleomorphism
Why is cell signalling important?
Required for:
- Movement
- Growth
- Metabolism
- Development
- Immune response
How is signal specificity achieved?
- 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
Autocrine
self-signalling; direct feedback on the cell that provduced the signal.
Paracrine
the signal has an effect on a cell nearby.
Endocrine
the effect is on a distant cell. The signalling molecules travel in the bloodstream.
Cytokines
soluble proteins or glycoproteins produced by cells. Important signalling molecules, esp. in inflammation and innate immunity.
What does pleiotrophy refer to?
the property of a single cytokine to be able to have different effects on different cells.
Describe cell signalling by gap junctions
- Cells communicate via cytoplasmic bridges
- This allows signalling molcules to pass between cells without being secreted into extracellular fluid
- Contact-dependent
Pros and cons of signalling via gap junction
✅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
Describe cell signalling by synaptic transmission
Communication between neurones involves chemical messenger across short synaptic cleft.
Pros and cons of cell signalling by synaptic transmission
✅ System can be activated very quickly
❌ Hardwiring is expensive - requires much energy to build and maintain
❌ Possibly vulnerable - if damaged, is hard to repair
Describe receptor-mediated signalling
- Sometimes cell-to-cell contact is required, however sometimes long-distance communication is possible
Pros and cons of receptor mediated signalling
✅ Can signal over long distances
✅ Signal specificity can be achieved
❌ May take time to elicit a response
What type of cell signalling is shown here?
Autocrine
What type of signalling is shown here?
Paracrine
What type of signalling is shown here?
Endocrine
What property of cytokines is shown here?
Pleiotrophy
What property of cytokines is shown here?
Redundancy: two or more cytokines may have the same/similar effect.
What are the effects of inflammation?
- Rubor
- Calor (heat)
- Swelling
- Pain (dolor)
- Loss/lack of function
Acute inflammation
normal response to most forms of injury/infection. Subsides once the infection is removed.
Chronic inflammation
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)
Inflammatory response
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
Describe the process of acute inflammation
- infection/tissue damage or injury stimulates cytokine production by the eptihelium
- Cytokine production stimulates other resident cells and attracts mast cells
- Histamine (e.g. as secreted by mast cells) as well as other vasoactive substances increase vascular permeability
- Chemokines attract neutrophils and monocytes which migrate out of the blood vessel
- Acute phase reactants (a.k.a. APPs) are present in the blood serum. They are important mediators of the inflammatory process.
What are the first cells at the site of inflammation (after mast cells)?
Neutrophils
Describe the inflammatory cascade
- 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
What are the effects of histamines?
- 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
What is diapedesis?
The process by which leucocytes reorganise their cytoskeletons to move between gaps in the endothelium and pass into the tissue.
Outline the effects of inflammation on local vasculature
- 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
What are acute phase proteins and where are they produced?
- 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
What is a granuloma and how is it formed?
- 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
- Macrophages receive persistent stimulation
- Summon more macrophages
- Chronically stimulated inflammatory cells aggregate; there is a collection of modified macrophages (=epitheliod cells) and a surrounding zone of lymphocytes
