Review of the innate system Flashcards
What does the innate system do?
Innate immunity keeps the pathogen under control and essential for survival for the adaptive to kick in.
Resolution of infection requires both adaptive and innate immune responses
No specific antigen recongition
- involves recongition of broad features of different classes = PAMPs
What are PAMPs?
Pathogen-associated molecular patterns
- Present only on pathogens and not on host cells
Essential for survival of pathogens
Invariant structures shared by entire class of pathogens
Examples:
- Gram-negative bacteria - lipopolysaccharides found in outer membrane
- Gram-positive bacteria - teichoic acid, lipoteichoic acid found in outer membrane
- Bacterial flagellin
- Abnormal nucleic acids - viruses
What are PRRs?
Pattern recongition receptors
- Host factors that specifically recognise a particular type of PAMP
- Germ-line encoded (same in everybody)
Several classes:
- Extracellular - recognise PAMPs outside of a cell and trigger a co-ordinated response to the pathogen
- Intracellular - recognise PAMPs inside a cell and act to co-ordinate a response to the pathogen
- Secreted - act to tag circulating pathogens for elimination
What are the different components to the innate immunity system?
- Inflammatory response
- Phagocytes
- Complement
- Cytokines, chemokines and anti-microbial peptides
- Natural killer cells
Describe the inflammatory response in the innate response
- Generic defence mechanism whose purpose is to localize and eliminate injurious agents and to remove damaged tissue components
- Enhances permeability and extravasation
- Neutrophil recruitment
- Enhanced cell adhesion
- Enhance clotting
- Triggered by the release of pro-inflammatory cytokines and chemokines at the site of infection
Describe the role phagocytes have in innate immunity
Phagocytosis - material is destroyed in lysosomes
Infections can trigger a macrophage activation - activated macrophages produce cytokines and chemokines to stimulate both innate and adaptive immune responses - triggers the inflammatory response and can promote a local anti-microbial state
Peptides from broken down pathogens can be presented through MHS and promote the development or recall of an adaptive T cell response
How do phagocytes know what to eat?
- detecting phosphatidylserine on exterior membrane surface (of cells apopsitisng)
- detecting aptical sugars on cell surfaces
- passive sampling
- scavenger receptors
- detecting complement proteins bound to surface
Describe the complement system
System which predates the development of the adaptive response
Complement proteins act as a secreted PRRs and can be activated by a range of PAMPs
How do phagocytes know when they are infected and when to produce cytokines and chemokines?
PAMPs are recognised by a distinct group of receptors:
- Toll-like receptors bind to LPS and lipoproteins –> inflammtation and cytokine release
- NOD-like receptors –> peptidoglycan from gram positive and negative bacteria –> inflammation and cytokine release
- RIG-like receptors bind to dsRNA –> type 1 interferon production
What are cytokines?
Act to modify the behaviour of cells in the immune response
Most of these are called interleukins
Interferons = main anti-viral cytokines
- Induced by viral infection
- Offer cross-protection
What are chemokines?
Act as chemotactic factors - they create concentration gradients which attract specific cell types to a site of production/infection
Whats the interferon system?
What are Anti-microbal peptides?
AMPs
- Secreted short peptides
- Usually work by disrupting cell wall leading to lysis
- Some are induced by bacterial infection
- Offer broad protection
What are natural killer cells?
White blood cells - lymphocyte-like but larger with granular cytoplasm
Kill certain tumour and virally infected cells
Target cell destruction is caused by cytotoxic molecules called granzymes and perforins
They are activated by loss-of-self, and ability to recognise and lyse virally infected cells and certain tumour cells
Selectivity is conferred by LOSS of self MHC molecules on target cell surfaces and up-regulation of activating ligands
What happens if a natural killer cell detects no MHC class 1 receptor on a pathogen?