Phagocytosis and pattern recognition Flashcards
What are 2 main cells involved in phagocytosis ?
- neutrophils
- macrophages
Describe neutrophils
- must be recruited from the circulation
- must bind directly to the pathogen
Describe macrophages
- can be tissue resident or recruited from the circulation
- must bind directly to the pathogen
- can also cause cytokine and chemokine release
Which complement proteins must be present for phagocytosis to occur ?
- both neutrophils and macrophages have a receptor on their surfaces which allow them to C3b
- C5a and C3b need to bind in order for phagocytosis to occur
Describe the process of phagocytosis
1) antibodies or complement proteins bind to their receptors causing a signalling cascade to be initiated
2) the cell membrane will form feet like projections called pseudopodia
3) this involves cytoskeleton rearrangement
4) bacteria will be engulfed to form a phagosome
5) phagosome will bind to a lysosome to form a phagolysosome
6) the lysosome will release its contents into the the phagolysosome
7) this will decrease the pH of the phagolysosome and release enzymes which break down the pathogen
Describe the oxygen dependent pathway of degradation
- occurs in neutrophils
- involves NADPH oxidase
- this converts molecular oxygen into reactive oxygen species
- examples of ROS include superoxide, hydrogen peroxide and myeloperoxidase
- reactive oxygen species are highly toxic to microorganisms
Describe the oxygen independent pathway of degradation
- occurs in both neutrophils and macrophages
- lysosomes release their contents into phagosomes which contain various antimicrobial peptides : lysozymes, defensins and enzymes
Describe differences in phagocytosis between neutrophils and macrophages
Neutrophils :
- the cellular debris is released to the local environment via exocytosis and this enhances the inflammatory response
- following phagocytosis neutrophils die and release NET to help kill further bacteria
Macrophages :
- express part of the broken down pathogen on the cell surface in a molecule called LHC class 2
- they also release cytokines
What are pattern recognition receptors ?
Recognises 2 main classes of molecular patterns :
- PAMPs (found on microbes)
- DAMPs (damage self cells)
Give examples of different pattern recognition receptors
- Toll like receptors
- Cytosolic PRRs
- NOD like receptors
Describe Toll-like receptors
- they are single pass transmembrane receptors
- have a leucine rich extracellular domain
- they are homo or heterodimers
- found on immune and non immune cells
- they recognise conserved molecular patterns
How do Toll-like receptors work ?
- all TLRs except TLR 3 signal via MyD88 TRAF6
- TLR 3 signal via TRIF TRAF6
Describe the role of extracellular TLRs
- extracellular TLRs need to be able to respond to both gram positive and gram negative bacteria
- gram positive bacteria have a thick external layer of peptidoglycan rich in triacyl and diacyl lipopeptides
- TLR2 is central to detecting these peptides
- TLR 1/2 detects triacyl lipopeptides
- TLR 2/6 responds to diacyl lipopeptides
- TLR 2 detects peptidoglycan
- gram negative bacteria have an outer membrane made up of LPS which is recognised by TLR 4
- TLR 5 binds to flagella of bacteria
- TLR 10 detects listeria and influenza (inflammatory)
- All other TLRs are proinflammatory
Describe the role of intracellular TLRs
- intercellular receptors recognise nucleic acids from bacteria and viruses
- also detect self DNA which has escaped the nucleus
- TLR 3 detects double stranded viral RNA, small interfering RNA and self RNA from damaged cells
- TLR 7 recognises single stranded viral RNA
- TLR 8 responds to both bacterial and viral RNA
- TLR 9 binds to CpG-DNA which is found in bacteria and viruses
Describe NOD-like receptors
- detect both PAMPs and DAMPs
- important in producing inflammasomes
