Exam 1: Inflammation I

Question 1

Features of innate immunity recognition

Answer 1

Recognize structures that are characteristic of microbial pathogens and are not present in mammalian cells

Recognize microbial products essential for microbial survival

Receptors of innate immune system are encoded germline

Question 2

PAMPs

Answer 2

Pathogen associated molecular patterns

Question 3

PAMPs flowchart

Answer 3

Structures of microbes, bacteria, viruses, fungi, protozoa –> PAMPs –> MAMPs –> innate immune system (PAMPs and MAMPs recognition)

Question 4

MAMPs

Answer 4

Microbe associated molecular patterns

Question 5

PRRs

Answer 5

Pattern recognition receptors

Receptors that recognize PAMPs

Question 6

PRR functions

Answer 6

Proinflammatory signals

Cytokine release

Phagocytosis

Question 7

PRR families

Answer 7

Toll like receptors (TLRs)
NOD like receptors (NLRs)
RIG like receptors (RLRs)

Question 8

NOD and RIG

Answer 8

NOD - nucleotide-binding oligomerization domain

RIG - retinoic acid inducible gene

Question 9

TLRs

Answer 9

Recognize PAMPs

Expressed in macrophages, dendritic cells, and mast cells

Found in epithelium exposed to external environment

Intracellular endosomal membranes (TLR3, TLR7, TLR9)

Each TLR detects a different set of PAMPs

Question 10

PAMPs detected by TLRs

Answer 10

LPS - lipopolysaccharides –> detected by TLR4
Peptidoglycans
Bacterial DNA and RNA
Flagellin –> detected by TLR5
Profilin-like protein - found in some protozoa

Question 11

Binding PAMPs to TLRs generates signaling cascade involving what 3 signaling molecules

Answer 11

Interleukin-1 (IL-1)
Interleukin-6 (IL-6)
Tumor necrosis factor-a (TNF-a)

Question 12

NLRs

Answer 12

NOD like receptors

Cytosol receptors - inside cell, recognize PAMPs in cell

Second line of detection of bacteria and viruses that make way into cytoplasm

Receptors are not membrane bound - float into cytoplasm

Question 13

Most important NLRs

Answer 13

NOD1 and NOD2 –> bind to bacterial peptidoglycans

NOD1 and NOD2 initiate signaling cascades that results in NF-kB leading the expression of proinflammatory cytokines and chemokines

Question 14

NF-kB

Answer 14

Nuclear factor-kB

Question 15

RLRs

Answer 15

RIG like receptors

RNA helicases

Detect presence of viral RNA (double stranded RNA and single strand RNA containing 5’ triphosphate)

Intracellular signaling results in NF-kB activation and expression of type I interferon

Question 16

Inflammasome

Answer 16

Assembled by activation of TLRs and NLRs

Produces activation of caspases

Caspase 1 activates/matures pro-cytokines

Question 17

Mannose receptors (MR, CD206)

Answer 17

MR present in phagocytic cells

Question 18

Example of phagocytic cell with MR and bacteria

Answer 18

Bacterium has mannose, phagocytic cell has mannose receptors

When one of the receptors binds to the bacteria, all other receptors come together

Mannose receptor sends signal inside phagocytic cell - rearrangement of cytoplasm

So bacterium completely covered by phagocytic cell membrane

Create phagosomes around bacterium

Enzymes released and bacterium killed

Question 19

DAMPs

Answer 19

Damage associated molecular patterns

Question 20

Example of DAMP

Answer 20

High mobility group box protein 1 (HMGP-1) –> potent inducer of inflammation

Question 21

Extracellular DAMPs

Answer 21

Released when tissue damage

Hyaluronic acid
Heparan sulfate
Fibrinogen
Collagen derived peptides
Fibronectin
Elastin

Question 22

Intracellular DAMPs

Answer 22

Released when cells die by apoptosis

HMGB1
Uric acid
Chromatin
Adenosine
Galectins
S100 proteins
Cathelicidins
Defensins
N-formyl peptides
Lactoferrin
Heat-shock proteins

Question 23

DAMPs and PAMPs summary

Answer 23

When macrophages activated –> produce chemokine –> promote inflammation and works as feedback on stimulation for macrophage

Question 24

Chemokines

Answer 24

Attraction of inflammatory cells

Question 25

Cytokines

Answer 25

Activation properties of cells

Simulate cells

Activation activities on pro-inflammatory cells

Make phagocytic cells more active