IMM2011 Lecture Notes - Lecture 3: Tlr3, Innate Immune System, Lipopolysaccharide
9 Jun 2018
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WEEK 2 :L1- Innate Immunity
what is meant by the term innate immunity:
- Innate immunity is defence that is always present in a normal host cell,
- it consist of numerous physical , cellular and soluble features that are ready to
recognize and eliminate microbes and dead cells .
- they are prepared to combat microbes immediately upon infection without the need
for an antigen and that occurs between about 0-4 hours.
- it consist two types of reaction , which include inflammation and antiviral
defence.Furthermore it responds in the same way to repeated encounters of
microbes and does not remember any previous encounter with it.
-immediate form of innate immune activation (0-4hr) upon infection involves
recognition by performed , non- specific and broadly specific effectors , resulting in
the removal of infectious agents.
- On the other hand early induced innate response (early 4-96 hours) occurs
following infection and involves recognition of PAMPS and the activation of effector
cells and inflammation thus resulting in the removal of infectious agents
-
key structures of microbes that are defined as PAMPS:
- The following structures are unique to microbes and are not found in the mammalian
cell which is therefore recognised as non- self molecules.
Flagella: found on bacteria
Membrane component: all bacteria contains peptidoglycan in their cell wall , which is
shared across gram positive and gram negative bacteria.
Gram positive bacteria: lipoteichoic acid
Gram negative bacteria: lipopolysaccharide and flagellin
Lipopolysaccharide:
DsRNA- virus and bacteria contain double stranded rna and 5 triphosphate rna .
DNA: microbial dna is unmethylated CPG nucleotide which is not found on mammalian dna.
Fungi: contains b- glycan, mannans and zymosan which are not found on mammalian cell.
why PAMPS are good targets for innate immunity:
- Pathogen associated molecular pattern(PAMPS) are structures on microbes that are
essential for their infectivity and colonisation of the host cell
- These are shared by microbes of the same type. Which makes it easier for innate to
target these and thus causes the microbes to lose their functionality as these
structures are key for survival , infection and colonisation.
key structures on our cells that are referred to as
1) Pattern Recognition
Receptors
PRR: location match of the receptor
determine its specificity for the type
of microbes.
TLR: found intracellularly on and on
cell surface .There are about 10 Toll
like receptors which are all similar in
structure but have different
specificity.
C- type lectin (sugar) receptors:
Found on the extracellular surface
and targets fungal infection
NOD like receptors: large family of
protein found intracellularly and recognise pamps and damps that come into cell.
RIG like receptors: located intracellularly these are specific for antiviral responses.
where the TLR PRRs may be found and why this is useful
TLR can either be found on cell surface , these are for bacterial protein, lipid and
polysaccharides that are present in the bacterial cell wall.
- TLR 4- which recognises and binds to LPS
- TLR5 which binds to flagella
- TLR can also be found inside the cell such as TLR3 which recognises dsRNA that is
found intracellular on the pathogen.
key downstream actions that can occur in a cell following a response
to PAMPS
- Following activation of NOD like receptors leads to the production of inflammasome.
- Cytokine IL-1 is produced which initiate the process of inflammation to recruit all the
cells to the site of action.
- Recognition of microbes: by the toll- like receptors leads to production of cytokines ;
reactive oxygen intermediates (ROIs) , overall resulting in the killing of microbes
