6.5.3 Principles of Innate Immunity Flashcards
What are some mechanisms for protection of epithelial surfaces?
skin barrier
fatty acids in sweat and sebum
intact mucous membranes
lysozyme in secretions
mucous and mucociliary escalator
acid in stomach
commensal microflora
What are the mechanisms protecting mucous membranes?
Physical properties:
- mucociliary escalator, peristalsis
-coughing and sneezing
-vomiting and diarrhoea
Secretions:
- physical properties (washes away organisms)
- anti-microbial properties (e.g. lysozyme)
Commensal microflora (microbiome)
How does innate immunity detect foreign microbial elements causing infection?
Uses pattern-recognition receptors (PRRs)
Pathogen-associated molecular patterns (PAMPs)
- Lipopolysaccharide
- Peptidoglycans
- Mannose
Where can the PRRs be found?
intracellular - cytoplasmic (NOD receptors)
in endosomes - vesicular
on the cell surface - membrane-bound (Toll-like receptors)
all the three upper cause phagocytosis and inflammation
What are the types of Toll-like receptors?
TLR-2: Peptidoglycan from G+ve bacteria
TLR-4: LPS from G-ve bacteria
TLR-5: Flagellin
TLR-9: Prokaryotic DNA
TLR-3, TLR-7: virus nucleic acid
cause cell signalling and activation
How can innate immune system detect viruses?
What is the response?
no structural PAMPs so not like microbes
but can be detected by presence of double stranded RNA produced during replication (not found in mammalian cells)
cells respond by producing interferons
What do the type 1 interferons do?
Resistant to viral replication
infected cells alert their friends
the cells turn on their viral defence systems
What do Natural Killer cells do?
Recognise decreased levels of MHC molecules on host cells
Recognise a ‘symptom’ of viral infection
What does the NOD2 receptor respond to?
detects muramyl dipeptide - breakdown product of bacterial cell walls
Outline the process of phagocytosis
1) endocytosis
2) phagosome formation
3) enzymes assemble in the phagosome membrane and pump in oxygen free radicals toxic to bacteria
4) lysosome containing defensins, lactoferrin and acid protease enzymes fuse with the phagosome releasing their content
5) H+ ions pumped into the phagosome which becomes increasingly acidic
6) acid proteases become active and the organism is digested
What can be found in lysosomes used for phagocytosis?
Defensins - cationic anti-microbial peptides that damage bacterial cell walls
Lactoferrin - binds and chelates free iron, which is required for bacterial growth
Acid proteases - digestive enzymes active at a low pH
What are the inflammatory mediators?
Histamine
Pro-inflammatory cytokines
Lipid mediators of inflammation
What are the localised effects of inflammatory cytokines?
Vasodilation
Increased capillary permeability
Influx of white blood cells
Why is inflammation important?
allows for targeting WBC from blood stream to the site of infection
What are the systemic effects of inflammatory cytokines?
Hypothalamus - fever
Liver - Acute phase response
Bone marrow - neutrophil and monocyte mobilization
