Lecture 1 - Innate recognition Flashcards
Three main ways of defending against pathogens
- Barriers - antimicrobial enzymes, antimicrobial peptides, complement systems, physical barrier
- Innate immune effector mechanisms
- Adaptive immune response
Inflammation: is it good or bad
Good - used to aid destruction of pathogens
Bad - chronic inflammation may damage its own body
Innate vs adaptive immunity: the molecules involved
Innate:
* Macrophages
* Neutrophils
* Dendritic cells
* Innate lymphoid cells
* NK cells
Adaptive:
* NK-T
* B cell
* T cell
PAMPs: what are they and what examples of them are there?
Pathogen-associated molecular patterns
- Bacterial component: LPS, Peptidoglycan,Flagellin, etc
- Single stranded viral RNA (e.g. SARS-Cov-2)
- Double stranded viral DNA (e.g. Herpes virus)
DAMPs: what are they, how are they formed, and what examples are there?
Damage associated molecular patterns
Motifs that are shielded from the immune system until the cell is injured - they then act as a signal for the immune system
- Heat Shock Proteins (HSPs),
- Uric acid crystals (Gout),
- ATP,
- DNA,
- β-Amyloid (Alzheimer),
- Some cytokines (e.g. IL-1α, HMGB1)
PRRs: what are they, what do they do, where are they present, and what do they result in?
Pattern recognition receptors
Recognise PAMPs/DAMPs
Cell surface (TLR, C-lectin, etc) or intracellular (RLRs/NLRs/cGAS/STING)
- Phagocytosis/ROS production
- Chemokine/cytokine production
Cytokines: what are they, do they only promote inflammation, and what may happen if balance isn’t maintained?
Chemical messengers
Can be pro or anti-inflammatory
Imbalance - disease likely caused
Cytokines: what examples are there?
- IL-1β
- IL-6
- IL12
- TNF-alpha
- CXCL8 (IL8)
TLRs: what are they, where does their name come from, and what do they have?
Toll-like receptors
Receptors that are similar to Toll receptors in drosophila
- Extracellular domain - contains LRR (leucine rich repeats)
- Transmembrane domain
- Intracellular domain
TLRs: are they all the same?
Bacterial/fungal TLRs have
?? watch lecture
TLRs: what do they do and how do they do what they do?
Activate transcription factors (NF-kB, AP-1 and IRF) to induce expression of cytokines and interferon - They can stimulate anti-viral or anti-bacterial responses
Watch leccy?
RLRs: what are they, ?? leccy, what immune function do they do, what types are there, and what do they each specifically recognise?
RIG-I-like receptors
RIG-like helicases (retinoic acid inducible gene-1):
Cytoplasm viral RNA recognition
Watch leccy for process
RIG-1: recognizes mainly ssRNA.
MDA-5: Mainly recognizes dsRNA
MAVS (adaptor protein) - mitochondrial membrane
cGAS
cGAS (cyclic-CMP-GMP synthase)
Sensor of intracellular infection
Self-recognition (self DNA)
cGAS (Cyclic GMP-AMP synthase):
contains a nucleotidyltransferase domain and two major DNA-binding domains.
absence of DNA, cGAS exists in an autoinhibited state
- Recognises DS viral DNA
- cGAS activated - produces cGAMP from GTP/ATP
- cGAMP activates STING
STING
STING (stimulator of interferon genes)
Senses cyclic dinucleotides (cGAMP)
Present on ER membrane
- Activates TBK1
- TBK1 phosphorylates IRF3
- IRF3 enters nucleus and induces type I interferon gene expression
Sensor of intracellular infection
Self-recognition (self DNA)
NLRs
Nod-like receptors (NLRs)
PAMPS and DAMPs (self and non-self)
Inflammasome forming
NLR-A: acidic transactivating domain (not a PRR!)
NLR-B: BIR-domain containing
NLR-C: CARD-domain containing
NLR-P: Pyrin-domain containing
Watch leccy
