Lecture 11. The Cellular Arm of the Innate Immune Response Flashcards
What are the three major classes of phagocytes?
Neutrophil, Eosinophil, Macrophage
What are neutrophils and Eosinophils?
Granulocytes: named because their cytoplasm is granular
What do neutrophils do?
They phagocytose and destroy microorganisms, especially bacteria, and thus have a key role in innate immunity to bacterial infection
What are properties of neutrophils?
Short-lived cells
Abundant in blood
Not present in normal healthy tissues
What are neutrophils rapidly recruited by?
Activated macrophages
Peptide fragments of cleaved complement proteins
And by some PAMPs
How do macrophages function?
They recognise and remove senescent, dead, and damaged cells in many tissues, and are able to ingest large microorganisms such as protozoa
What do Eosinophils help to do?
Destroy parasites, modulate allergic inflammatory responses
What is it called when a phagocyte’s plasma membrane surrounds the pathogen and engulfs and encloses it?
Phagosome
What are ‘granules’?
Dense membrane-bound lysosomal derivatives
They fuse with the phagosome membrane and release their contents (lysozyme, acid hydrolases) in an attempt to digest the pathogen’s cell walls
What is a respiratory burst?
A transient increase in oxygen consumption
What does NADPH oxidase complexes do to phagosomes?
Produce highly toxic oxygen-derived compounds such as superoxide, hypochlorite and hydrogen peroxide after a respiratory burst
What do dead neutrophils and pathogens form?
Pus
How does inflammation aid in the killing frenzy?
Blood vessels dilate, leading to local swelling and the accumulation of components of the complement cascade
What can go wrong with inflammation?
Systemic release of inflammatory cytokines can lead to excessive blood vessel dilation, resulting in sudden lowering of blood pressure (shock)
If widespread inflammation, septic shock can occur
What does dsRNA do?
Induces interferon (IFN) production
What are interferons?
Interferons are the most important cytokines in the virology context: IFN-α and IFN-β are produced by all cells in response to viral dsRNA
What do interferons do?
- Make the virally-infected cell and its neighbours into much less efficient factories for making new viruses
- Limit viral spread by promoting apoptosis (programmed cell death – in a couple of slides) of the infected cell
- Upregulate the display of viral peptides on the outer membrane of the infected cell: this provides signals for recognition by activated T cells
- Stimulate expression of the immunoproteasome to process and destroy viral proteins
- They also provide a call for help, attracting natural killer cells and also activating macrophages
- They also fight cancers
What do natural killer cells do?
NK cells recognise their targets by monitoring the level of expression of these molecules at the cell surface
NK cells are also attracted to virally-infected cells by IFNs
NK cells then persuade such cells to commit suicide: the target cells die by apoptosis
Process of NK cells persuading apoptosis
Apoptopic signals given
Mild convolution, chromatin compaction, cytoplasmic condensation
Nuclear fragmentation, cell ‘blebbing’, cell fragmentation
Phagocytosis