B1 Pathogen Recognition Flashcards
Define Inflammatory inducers & give examples
= chemical structures that indicate the presence of invading microbes or the cellular damage produced by them
e.g. Bacterial lipopolysaccharides, ATP, urate crystals
Define Sensor cells
= detect Inflammatory inducers by expressing various innate recognition receptors & in response produce mediators that act directly in defense or further propagate the immune response.
e.g. Macrophages, neutrophils, dendritic (via PAMP binding)
Give examples of mediators
cytokines, cytotoxicity
define antimicrobial agents and give examples (6)
Secreted by cells such as epithelial cells and phagocytic cells, are usually made as inactive proproteins that require a proteolytic step to complete their activation
e.g. Mucins, Lysozyme,
Defensins, Cathelicdins,
Histatins, RegIII family
Define mucins & lysozyme
Mucins: may prevent adhesion to epithelium by microorganisms
Lysozyme: glycosidase (sugar cleaving enzyme) that attacks peptidoglycan in bacterial cell wall (degrades)
Define defensins & cathelicidins
Defensins: disrupt cell membranes of bacteria and fungi via pore formation
Cathelicidins: disrupt cell membrane of wide range of microorganisms
Define Histatins & RegIII
Histatins: active against pathogenic fungi
RegIII family: C-type lectins, which target peptidoglycans, promoting pore formation
Name & define Soluble receptors:
▪ Mannose-binding lectin: recognize sugars, e.g. mannose; fucose
▪ Ficolin: recognizes oligosaccharides containing acetylated sugars
▪ C-reactive protein: recognizes phosphorylcholine
Name Pathogen Recognition Receptors:
- C-type lectin family, e.g., Dectin-1: recognises b-1,3-linked glucans
mannose receptor: may recognise mannose-containing structures on pathogens + play role in clearance of host proteins
2.Scavenger receptors: heterogenous, recognise various anionic polymers & acetylated low-density lipoproteins; may bind pathogen (e.g., bacterial cell wall) or host products - Complement and Fc receptors: recognise Complement-coated and antibody-coated organisms
- Toll-like receptors: recognise molecular patterns not found in healthy vertebrate cells
Name the 4 signaling adapters for TLR
MyD88 (myeloid differentiation factor 88) ((present in all except TLR3))
MAL (MyD88 adaptor-like, also known as (TIRAP, for TIR- containing adaptor protein),
TRIF (TIR domain-containing adaptor-inducing IFN-β), TRAM (TRIF-related adaptor molecule).
define NOD-like receptors
NLRs: intracellular sensors of bacterial infection and cellular damage/ promote activation of signaling e.g. NFkB to induce the expression of pro-inflammatory genes
which cells are NOD expressed in
cells routinely expressed to bacteria –> epithelial cells, macrophages, dendritic cells
CARD
caspase recruitment domain - recognize bacterial cell wall peptidoglycan fragments
how do CARD and NOD work together
card on nod proteins can dimerise with CARD on other proteins to induce cell signaling
define NLPR and what do they contribute to?
Pyrin-containing NOD-like receptors, contribute towards inflammasome (drives pro-inflammatory cytokine production & induces cell death)
what step is required for production of inflammatory cytokines by the inflammasome
Priming step.
For cytokine production, cells must produce and translate the mRNAs that encode the pro-forms of IL-1b and IL-18. (needs to make these pro-inflammatory cytokines)
The priming step can result from TLR signalling, which may help ensure that inflammasome activation proceeds primarily during infections.
Formed after simulation of NOD-like receptors.
Define RIG-I-like receptors
sense viral RNAs produced within cells as opposed to those that enter cells from the endocytic pathway that are recognised by TLRs
(activation of RIG-I-like receptors results in type I interferon production)
Define Cytosolic DNA sensors
multi-component pathway, incorporating cGAS (cyclic GAMP synthase) and STING, which acts as an innate sensor of pathogen cytoplasmic DNA
(activation of pathway results in type I interferon production)