Exam 1: Inflammation I Flashcards
Features of innate immunity recognition
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
PAMPs
Pathogen associated molecular patterns
PAMPs flowchart
Structures of microbes, bacteria, viruses, fungi, protozoa –> PAMPs –> MAMPs –> innate immune system (PAMPs and MAMPs recognition)
MAMPs
Microbe associated molecular patterns
PRRs
Pattern recognition receptors
Receptors that recognize PAMPs
PRR functions
Proinflammatory signals
Cytokine release
Phagocytosis
PRR families
Toll like receptors (TLRs)
NOD like receptors (NLRs)
RIG like receptors (RLRs)
NOD and RIG
NOD - nucleotide-binding oligomerization domain
RIG - retinoic acid inducible gene
TLRs
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
PAMPs detected by TLRs
LPS - lipopolysaccharides –> detected by TLR4
Peptidoglycans
Bacterial DNA and RNA
Flagellin –> detected by TLR5
Profilin-like protein - found in some protozoa
Binding PAMPs to TLRs generates signaling cascade involving what 3 signaling molecules
Interleukin-1 (IL-1)
Interleukin-6 (IL-6)
Tumor necrosis factor-a (TNF-a)
NLRs
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
Most important NLRs
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
NF-kB
Nuclear factor-kB
RLRs
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
Inflammasome
Assembled by activation of TLRs and NLRs
Produces activation of caspases
Caspase 1 activates/matures pro-cytokines
Mannose receptors (MR, CD206)
MR present in phagocytic cells
Example of phagocytic cell with MR and bacteria
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
DAMPs
Damage associated molecular patterns
Example of DAMP
High mobility group box protein 1 (HMGP-1) –> potent inducer of inflammation
Extracellular DAMPs
Released when tissue damage
Hyaluronic acid Heparan sulfate Fibrinogen Collagen derived peptides Fibronectin Elastin
Intracellular DAMPs
Released when cells die by apoptosis
HMGB1 Uric acid Chromatin Adenosine Galectins S100 proteins Cathelicidins Defensins N-formyl peptides Lactoferrin Heat-shock proteins
DAMPs and PAMPs summary
When macrophages activated –> produce chemokine –> promote inflammation and works as feedback on stimulation for macrophage
Chemokines
Attraction of inflammatory cells
Cytokines
Activation properties of cells
Simulate cells
Activation activities on pro-inflammatory cells
Make phagocytic cells more active
