Innate immunity: the induced response Flashcards
State two cell types that overlap between innate and adaptive immunity
gamma delta T cell
NK T cell
Phagocyte recruitment occurs in two stages
Describe 1. Rolling and extravasion
- cytokines dilate BVs
- chemokines attract monocytes and neutrophils to infections
- cell adhesion molecules (ICAM1 and 2) are upregulated on the endothelium which bind to integrins (family of adhesion molecules) on the leukocytes
Phagocyte recruitment occurs in two stages
Describe 2. Receptor mediated phagocytosis
- macrophage receptors recognise components of microbial surfaces
- microorganisms bound by phagocytic receptors on the macrophage surface
- microorganisms internalised by receptor- mediated endocytosis
- fusion of the endosome with a lysosome forms a phagolysosome in which microorganism is degraded
In phagocyte recruitement, which mediators facilitate arrest/adhesion
- Opsonins: ABs, collectins, complement components (C3B)
- Phagocytic receptors : complement, Fc, mannose, scavenger
By which mechanisms do antimicrobials work?
- Acidification: pH 3.5 -4
- Toxic O2 derived products: O2-, H202, .OH, OCl-
- Toxic nitrogen oxides
- Antimicrobial peptides : cathelicidins, a-defensins
- Enzymes: lysozymes
- Competitors: lactoferrin
What are neutrophil extracellular traps (NETs)?
- when activated some neutrophils undergo cell death (NETosis)
- during NETosis nuclear chromatin is released from cells trapping microorganisms aiding phagocytosis
State three PRR types in the innate immune system
PRRs - recognise PAMPs Toll like NOD like Rig-I like Cytosolic DNA sensors
PRRs recognise PAMPs and DAMPs, what can be said about these interactions?
- PAMPs recognition must focus on highly conserved and essential components of microbes i.e. cell wall structures and nucleic acid as microbes evolve quickly. Random mutations play a significant role in ability to survive and adapt due to speed at which they replicate
- Damage associated molecular patterns (DAMPs) are released from necrotic cells
Why are drosophilia toll receptors important?
Mammalian equivalent?
- important for development and immunity to the fungal and bacterial infections
- mammalian equivalient = toll like receptor
Describe the structure of toll like receptors and how it is suited to its activation
The TIR domain is a conserved stretch of approx. 200 AAs
The extracellular domain (LRR) is the site of pathogen binding
Convex surface of TLR1 and TLR2 have binding sites for lipid side chains of triacyl lipopeptide. Binding of each TLR to the same lipopeptide induces dimerisation, bringing their cytoplasmic TIR domains into close proximity.
Toll like receptors recognise exogenous and endogenous ligands.
Which TLRs are found on cell surfaces?
What are their ligands?
TLRs 1,2,4,5,6
Bacterial products :
- lipopolysaccharides
- flagellin
- lipoteichoic acid
Toll like receptors recognise exogenous and endogenous ligands.
Which TLRs are endosomal?
What are their ligands?
TLRs 3,7,8,9,10
Viral products:
- dsRNA
- ssRNA
- DNA
What does TLR signalling cause?
It induces genes that function in host defense e.g
- proinflammatory cytokines
- chemokines
- MHC and co-stimulatory molecules
- antimicrobial peptides and complement components
What is Waldenstrom macroglobulinemia ?
How can it be determined?
- Rare type of non-hodgkin lymphoma
- B cells make lots of IgM –> excessive bleeding, headaches, vision problems
- Lymphoma cells proliferating in bone marrow –> anaemia, neutropenia and thrombocytopenia
- MYD88 and CXCR4 are determinants
What happens in MYD88 deficiency?
Life threatening, often recurrent pyogenic bacterial infections
- improves with age due to a compensatory effect of adaptive immunity
