detecting and responding the pathogens Flashcards
Describe innate immunity
- rapid host defence against invading pathogens- within minutes
- does not change - born w it
-no requirement for memory - recognition of invading pathogens + activation of anti microbial response
what are the 4 steps of handling pathogens that are viruses?
- endocytosis
- cellular shut down
- self sacrifice
- cellular resistance
what molecular patterns can the innate immune system recognise?
- Highly conserved structures expressed by large groups of pathogens.
- Common biologic consequences of infection.
what does PAMPs stand for?
Pathogen associated molecular patterns
includes things like:
- bacteria
- virus
- parasite
- fungi
why is it important to recognise patterns?
To vastly expand the repertoire of ligands they can bind
what does DAMPs stand for?
Damage associated molecular patterns
what are DAMPs?
Endogenous molecules created to alert the host to tissue injury and initiate repair
name some examples of DAMPs
molecules
DNA
RNA
Extracellular ATP
Hyaluronic acid
Glucose
Fibrinogen
Fibronectin
Heat shock proteins
IL-1-a, IL-33
particles
Uric acid
Amyloid-b
Silica
Nanoparticles
Alum
Asbestos
Hemozoin
other
UVB
mutations
Why do we not recognise our own DNA and RNA and mount an innate response?
Our DNA and RNA is normally located where our pattern recognition receptors (PRRs) cannot access it
describe PRRs
Secreted and circulating receptors
Receptors on the cell surface and cell membranes
Receptors inside the cell (cytoplasmic)
What are cell associated PRRs
receptors that are present on the cell membrane or on organelles within the cytosol of cells
They are able to recognise a broad range of molecular patterns
what is the main family of cell associated PRRS
TLRs
how does TLR ( PAMPs) signalling work?
Different TLRs activate different signalling cascades depending on the pathogen being detected to tailor the immune response that is generated
give 3 examples of membrane bound PRRs
Mannose receptor - on macrophages (fungi)
Dectin-1 - widespread on phagocytes (beta glucans in fungal walls)
Scavenger receptors - on macrophages (wide variety of lipid-related ligands from pathogens or from host cells that are damaged, apoptotic or senescent
what are the three members that detect viral RNA in the cytoplasm?
- Retinoic acid-inducible gene I (RIG-I)
- Melanoma differentiated gene 5 (MDA-5)
3.Laboratory of genetics and physiology 2 (LGP2)
describe Retinoic acid-inductible gene I ( RIG-I)
- short dsRNA (up to 1 kb)
- 5’ triphosphate (5’ppp) caps (ss or ds RNA)
- e.g. influenza A and respiratory syncytial virus (RSV)
Describe Melanoma differentiated gene 5 (MDA-5)
long dsRNA (over 2kb) with no end specificity
- replication intermediates
- e.g. rhinovirus (RV)
describe Laboratory of genetics and physiology 2 (LGP2)
very high affinity for any dsRNA
- positive regulator of RIG-I and MDA5 signaling
what are NOD- like Receptors involved in? ( NLRs)
-sensing cytoplasmic bacterial pathogens and DAMPS
-regulation of inflammatory & cell death responses
how many NLRs genes are there in humans?
22
How are NLRs characterised?
Characterised by the presence of a conserved nucleotide-binding and oligomerisation domain (NOD / aka NACHT)
what are NLRs subdivided into?
4 subfamilies, based on N-terminal effector domains
Why don’t NLRs activate interferons?
NLRs detect predominantly intracellular bacteria and IFNs are anti-viral cytokines
what are NOD 1 & 2 activated by?
Activated by recognition of specific motifs (mostly muropeptides) present in bacterial peptidoglycan (PG)
