3. innate immunity Flashcards
neutrophils function
phagocytosis
reactive oxygen and nitrogen species
antimicrobial peptides
NETs: neutrophil extracellular traps
dendritic cells function
antigen presentation costimulatory cels reactive oxygen species interferon cytokines
macrophages function
phagocytosis inflammatory mediators antigen presentation reactive oxygen and nitrogen species cytokines complement proteins
natural killer cells function
lysis of viral-infected cells
interferon
macrophage activation
phagocyte recruitment: rolling and extraversion
cytokines dilate local blood vessels
chemokine attract monocytes and neutrophils to infection
cell adhesion molecules (ICAM-1, ICAM-2) are upregulated on endothelium - bind to interns on leukocytes
rolling, activation, arrest/adhesion, transendothelial migration
what is phagocytosis?
capture and digestion of foreign particles
performed by neutrophils and macrophages
opsonins
complement components (C3b)
collectins (mannose-binding lectin)
antibodies
phagocytic receptors
complement receptors
Fc receptors
mannose receptors
scavenger receptors
receptor mediated phagocytosis
active process initiated by binding to pathogen
macrophage receptors that recognise components of microbial surfaces
microorganisms bound by phagocytic receptors on macrophage surface
microorganisms are internalised
fusion of endosome with lysosome foreign phagolysosome
antimicrobial mechanisms of phagocytes
acidification toxic oxygen-derived produces toxic nitrogen oxides antimicrobial peptides enzymes competitors
neutrophil extracellular traps (NETs)
when activated, some neutrophils undergo a special form of cell death = NETosis
nuclear chromatin is released from cells
traps microorganisms, aiding phagocytosis
pattern recognition receptors (PRRs)
receptors able to recognise conserved structures
recognise pathogen-associated molecular patterns (PAMPs)
examples: toll like receptors, NOD-like receptors, Rig-1 like receptors, cytosolic DNA sensors
pathogen associated molecular patterns (PAMPs)
microbes evolve easily - must focus on highly conserved, essential components of microbes
e.g. cell wall structures, nucleic acids
damage associated molecular patterns (DAMPs)
molecules released from necrotic cells
drosophila toll receptor
mutagenesis work: rereleased 2 members of Toll family
dToll
18-wheeler
important for development + immunity to fungal/bacterial infections
mammalian equivalent = toll-like receptor
toll like receptor structure
extracellular: leucine-rich repeats (LCC) domain - site of pathogen binding
intracellular: TIR domain - stretch of ~200 amino acids
how do toll like receptors work?
form functional hetero/homodimers
binding of each TLR to same lipopeptide induces dimerisation - brings cytoplasmic TIR domain into close proximity
what to toll like receptors recognise?
bacterial products - lipopolysaccharide, flagellin, lipoteichoic acid, HSP70, fibrinogen, fibronectin
viral products - dsRNA, ssRNA, DNA
different TLRs recognise different PAMPs
what do TLRs signal?
induce genes that function in host defence
pro inflammatory cytokines
chemokines
MHC and costimulatory molecules
antimicrobial peptides and complement components
TLR signalling pathways
trip pathway
MAPKs
MyD88 dependent pathway
