Innate Immunity Flashcards
What is innate immunity? (and its characteristics)
It is a protective response to pathogens that does not require any previous exposure to the pathogen in question
It is rapid
It depends upon the recognition of conserved/invariant features of pathogens
It is relatively non-specific
It utilises germ line-encoded host receptors
It does not generate memory
EVERYTHING has innate immunity
What are PAMPs?
Pathogen recognition is through pathogen-associated Molecular Patterns (PAMPs)
Molecules present only on pathogens and not on host cells
Essential for survival of pathogens
Invariant structures shared by entire class of pathogens
What are examples of PAMPs?
Gram-negative bacteria; lipopolysaccharides (LPSs) found in outer membrane
Lipopolysaccharides are found on all gram-negative bacteria
Gram-positive bacteria; teichoic acid, lipoteichoic acid, peptidoglycan found in outer membrane
These repeated structures are examples of pathogen-associated molecular patterns
It’s not all about an organism’s cell wall though
Other examples of PAMPs include:
Bacterial flagellin
Abnormal protein glycosylation
Abnormal nucleic acids- viruses
What are PRRs?
Pattern recognition receptors (PRRs)
Host factors that specifically recognise a particular type of PAMP
They are germ-line encoded
There are several classes of PRR, but functionally they are either:
Extracellular- they recognise PAMPs outside of a cell and trigger a coordinated response to the pathogen
Intracellular (cytoplasmic)- they recognise PAMPs inside a cell and act to co-ordinate a response to the pathogen
Secreted- they act to tag circulating pathogens for triggering a process for elimination
What are your microbe entry barriers?
Sites of microbe entry are equipped with certain measures/barriers
Physical barriers:
Skin, mucosal surfaces
Chemical barriers:
pH, secreted factors
These aren’t really part of innate immunity
What are the different components of innate immunity?
The inflammatory response
Phagocytes- monocytes/granulocytes/neutrophils
Cytokines/chemokines these are the immune system’s hormones
Complement
Natural Killer cells
What is the inflammatory response and how does it work?
A generic defence mechanism whose purpose is to localise and eliminate injurious agents and to remove damaged tissue components
Enhanced permeability and extravasation
Neutrophil recruitment
Enhanced cell adhesion meaning that when they get to the site of infection they stay there
Enhance clotting attempting to cut off the site of infection- stop spreading
Triggered by the release of pro-inflammatory cytokines and chemokines at the site of infection
The chemokines create the concentration gradient to attract cells to the site of infection and the cytokines coordinate the immune response
What cells carry out phagocytosis?
Carried out in vertebrates by ‘professional phagocytes’:
Dendritic cells- they are major role players in helping us switch form innate to adaptive immunity
Macrophages- responsible for resolving quite a damage at the site of infection
Neutrophils- the major phagocytes in the inflammatory response otherwise not many normally there
What are the three distinct roles of macrophages and dendritic cells?
Phagocytosis- material is destroyed in lysosomes
Infections can trigger macrophage activation:
Activated macrophages produces cytokines and chemokines to stimulate both innate and adaptive immune responses
This triggers the inflammatory response and can promote a local anti-microbial state
Peptides from broken down pathogens can be presented through MHC (major histocompatibility complexes) and promote the development or recall of an adaptive T cell response
What are cytokines and chemokines?
Glycoprotein hormones that affect the immune response
Cytokines:
Act to modify the behaviour of cells in the immune response
Most of these are called interleukins (e.g. IL-1)
Interleukins, when they are released they are really good at triggering an enhanced inflammatory response, specifically IL-1
IL-2, when released, stimulates the division of T cells
Chemokines
Act as chemotactic factors- i.e. they create concentration gradients which attract (or occasionally repel) specific cell types to a site of production/infection
How do phagocytes recognise cells they need to digest?
Phagocytes have to be able to recognise what to eat
Phagocytes need to know when they are infected in order to produce cytokines and chemokines
The molecular recognition events are distinct i.e. they use different pattern recognition receptors
So how do phagocytes know what to eat?
Material to be “eaten” is recognised in a number of ways:
By detecting phosphatidylserine on exterior membrane surface- shouldn’t be on the outside (cells undergoing apoptosis have this)
By detecting “atypical sugars” (e.g. mannose, fucose, b-glucan) on cell surface
By detecting complement proteins bound to the pathogen surface
By Scavenger receptors which recognise other things like lipids which shouldn’t be on the outside of self cells
By “passive sampling”
What is the complement system/mechanism? How do you activate it?
A system of secreted proteins (these are PRRs) made in the liver that recognise PAMPs on the surface of microbes and ‘decorate’ or ‘tag’ them.
The microbes are then cleared by phagocytosis, ‘opsonised’ (completely covered)or they have holes punched in them
Three ways of activating:
1.Recognition of LPS and other PAMPs by the C1q component of ‘classical’ pathway
2.Non-host glycosylation is recognised by MBP and other lectins to activate the ‘lectin’ pathway
3.Membranes that are recognised as ‘non-self’ activate the ‘alternative’ pathway
Complement activation involves a proteolytic cascade
What is the interferon system and how does it work?
An antiviral response
So powerful if it didn’t exist viruses would overpower you really easily
Most viruses have genes needed to specifically fight the interferon system
So here we have a virus invading the cell
The virus will replicate quite easily and so the cell will die
The process of the cell dying will release many new virions
These viruses will now attempt to invade the neighbouring cells but, if the system works correctly, whilst the cell is making lots of new virus copies the cell detects the PAMPS using PRRs
It will up-regulate the synthesis of interferon
Interferon is secreted from these cells and they will bind to the receptor in neighbouring cells and that will trigger production of about 400 antiviral gene products
What are NK cells?
Natural Killer (NK) cells (Large granular lymphocytes)
4% white blood cells
Lymphocyte-like but larger with granular cytoplasm
Kill certain tumour & virally infected cells
Target cell destruction is caused by cytotoxic molecules called granzymes & perforins
Target cells get lysed or innards get digested by proteases that get injected into them by NK cells
What’s different with NKs is how they recognise infected cells
How are NK cells activated?
Natural Killer (NK) cells are activated by loss-of-self
NK cells possess the 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
Many pathogens down regulate MHC on the surface triggering the loss of MHC
The NK have receptors that detect MHC, if it does detect MHC it will not kill it
