L4 - Innate Immunity (sensing Microorganisms) Flashcards
Fill in the gaps: innate immunity
- recognises generic ________ _______
- limited _____ diversity
- not ______, receptors are ______ _____
- cells of the same lineage share same ___
- danger signals
- receptor
- adaptable, germ line encoded
- receptor
What are the 2 danger signals?
PAMPs (common evolutionary conserved pathogen molecules)
DAMPs (molecules produced by damaged host cells)
Fill in the gaps: Adaptive Immunity
- can recognise ___ _______ or _______
- very ____ receptor diversity
- ____, receptors created by _____ ______ or gene segments
- Any microbial or non-microbial molecules (antigens)
- large
- adaptable, somatic recombination
What is the complement t and how does it work to act against infection?
- oldest example of pathogen recognition mechanism
- collection of proteins that work together to protect from infection
3 main mechanism
- recruitment of immune cells
- label microbes for phagocytosis by other cells
- Lyses pathogens by punching holes
What are the 3 activation pathways of the complement pathway mechanism?
Alternative pathway and lectin pathway (direct pathogen recognition)
Classical pathway (via adaptive immunity and antibodies)
How does the alternative pathway work? What is the issue with it?
- C3b is spontaneously produced by C3 (always present and active)
- complement t effector mechanism activated
- C3b binds to amino and hydroxyl groups on microbes
These groups are also present on host cells so host has to shut down C3b activity
How does the lectin pathway work?
- mannose is a carbohydrate found on the surface of many common pathogens
- mannose binding lectin (MBL) recognises the microbes but does not bind to host mammalian cells
- MBL binds to mannose which is bound on pathogens and complement effector mechanism is activated
What is PAMPs and what is an example
Pathogen Associated Molecular Patterns
- e.g. mannose
What are the receptors on innate immunity that recognises PAMPs? What are some examples?
Pattern Recognition Receptors (PRRs)
- mannose binding lectin, TLR, RIG, NLR
What are examples of phagocytes? Do they have PRRs on their surface?
Macrophages and neutrophils, yes
What is the killing mechanism of phagocytes?
take up bacteria by engulfing and secreting toxins to digest the bacteria
What are sentinel cells and phagocytosis?
- use phagocytosis to sample the environment for microbes
- talk to T cells and show them any microbial molecules they’ve detected (antigens presenting cells, APC)
- activate T cells
Describe the macrophage?
- don’t move from infection site
- talk to T cells at infection site
- good killer
- good all rounder
Describe the dendritic cell as a sentinel cell
- migrate from infection site to lymph node
- talk to T cells in LN and infection site
- doesn’t kill
- specialised in talking with T cells
Where are macrophages sentinels found ?
All barrier tissue (skin, intestine, lungs)
What do macrophages as sentinels do in their resting rate?
- mop up apoptotic cells
- remove debris
- sample the environment
- scan for danger via PRRs
What is the first danger signal? How is it made? Is it a warning or infection
1st danger signal = tissue damage
PRRs recognise molecules released from damaged or necrotic cells (DAMPs, damage associated molecular patterns)
- only a yellow alert warning doesn’t mean infection
How do DAMPs prepare macrophages?
DAMPs activates complement not pathways and secretes cytokines. It becomes better at phagocytosis and express surface receptors for communicating with adaptive immune cells
What is the second danger signal?
PAMPs, all microbes express different PAMPs which are conserved so limited PRRs can recognise them. This means that germline endocarditis receptors can go and tell that you’ve been exposed to a microbe
What is the PAMPs in gram negative bacterial cell wall?
LPS (lipopolysaccharide)
What are other examples of bacterial PAMPs
Lipoteichoic acid (gram positive cell wall)
Unmethylated CpG DNA
Flagellin
What is the PAMPs in viruses and Fungi
- dsRNA, ssRNA
- cell wall glucans
Summary fill in the gap:
- single innate cell can express ____ PRRs
- PRRs transmit a ___ when they bind to their ligand (DAMPs or PAMPs)
- PRRs are both ____ and ____
- diff PRRS recognise ___ DAMPs/PAMPs
- multiple
- signal
- intracellular and extra cellular
- diff
What brings macrophages to their red alert? What r they like in red alert form?
- binding to PAMPs
- increased size, enhanced phagocytosis, release toxic molecules, better killer, releases cytokines
What brings macrophages from resting to yellow to red alert
Yellow
- DAMPs & cytokines
Or PAMPs
Red
- PAMPs & cytoines & T cells help (no full activation until we get signals from adaptive)
How is inflammation achieved through macrophages? What happens during inflammation?
They release pro-inflammatory cytokines (TNF-a) as a way of calling for help
- recruits immune cells to infection site, activate immune cells
- production of acute phase proteins
- head (better for immune cells bad for microbes)
What 2 immune cell is in charge of killers on call? How does it work?
Neutrophils
- recruited from blood to infection site
- phagocytosis of pathogens
- release destructive chemicals (granules)
- makes pus
NK cells
- produced cytokine interfering gamma which activates macrophages
How is inflammation initiated (macrophages + cytokines + NK cells and neutrophil)
- macrophages secretes cytokines (TNF a) to recruit neutrophikl and NK cells
- DAMPs and PAMPs also activate neutrohils and NK cells directly which releases more siganls (IFN-y) to macrophages
Which cytokine is released from macrophage and which is released from NK/neutrophil
TNFa from macrophages
IFN-y from NK
How is inflammation resolved using signals
- start to deactivate if neutrophil and NK cell stop getting DAMP/PAMP siganl
- neutrophil is short lived
What is systemic what is sepsis
- when infection get into blood
- fluid leaks into tissues leading to to septic shock
How does PAMPs act as toxins to induce TLR4 sepsis
- TLR4 is the PRR for LPS
- TLR4 polymorphism associate with increased susceptibility to sepsis
