B1 Pathogen Recognition

Question 1

Define Inflammatory inducers & give examples

Answer 1

= chemical structures that indicate the presence of invading microbes or the cellular damage produced by them
e.g. Bacterial lipopolysaccharides, ATP, urate crystals

Question 2

Define Sensor cells

Answer 2

= 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)

Question 3

Give examples of mediators

Answer 3

cytokines, cytotoxicity

Question 4

define antimicrobial agents and give examples (6)

Answer 4

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

Question 5

Define mucins & lysozyme

Answer 5

Mucins: may prevent adhesion to epithelium by microorganisms
Lysozyme: glycosidase (sugar cleaving enzyme) that attacks peptidoglycan in bacterial cell wall (degrades)

Question 6

Define defensins & cathelicidins

Answer 6

Defensins: disrupt cell membranes of bacteria and fungi via pore formation
Cathelicidins: disrupt cell membrane of wide range of microorganisms

Question 7

Define Histatins & RegIII

Answer 7

Histatins: active against pathogenic fungi

RegIII family: C-type lectins, which target peptidoglycans, promoting pore formation

Question 8

Name & define Soluble receptors:

Answer 8

▪ Mannose-binding lectin: recognize sugars, e.g. mannose; fucose
▪ Ficolin: recognizes oligosaccharides containing acetylated sugars
▪ C-reactive protein: recognizes phosphorylcholine

Question 9

Name Pathogen Recognition Receptors:

Answer 9

1. 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
2. Complement and Fc receptors: recognise Complement-coated and antibody-coated organisms
3. Toll-like receptors: recognise molecular patterns not found in healthy vertebrate cells

Question 10

Name the 4 signaling adapters for TLR

Answer 10

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).

Question 11

define NOD-like receptors

Answer 11

NLRs: intracellular sensors of bacterial infection and cellular damage/ promote activation of signaling e.g. NFkB to induce the expression of pro-inflammatory genes

Question 12

which cells are NOD expressed in

Answer 12

cells routinely expressed to bacteria –> epithelial cells, macrophages, dendritic cells

Question 13

CARD

Answer 13

caspase recruitment domain - recognize bacterial cell wall peptidoglycan fragments

Question 14

how do CARD and NOD work together

Answer 14

card on nod proteins can dimerise with CARD on other proteins to induce cell signaling

Question 15

define NLPR and what do they contribute to?

Answer 15

Pyrin-containing NOD-like receptors, contribute towards inflammasome (drives pro-inflammatory cytokine production & induces cell death)

Question 16

what step is required for production of inflammatory cytokines by the inflammasome

Answer 16

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.

Question 17

Define RIG-I-like receptors

Answer 17

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)

Question 18

Define Cytosolic DNA sensors

Answer 18

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)