Thursday, November 30, 2006

English Immunology Notes

He will focus on innate immunity and Toll-like receptors.
2 Innate immunity turns on and adapts adaptive immunity. Triggered by recognition of conserved molecular patterns.
4 LPS (lipopolysaccharide) exists only in bacteria.
7 Innate immune system should be perfect at recognition self vs nonself. SLE- lupus may have something wrong in toll-like receptor 9 which distinguishes human DNA from bacterial DNA.
10 Innate immunity- he focuses on signalling pathway. Opsonin is a word from the Greek language meaning “to prepare something to eat”- coat bacteria for easier ingestion.
15 Janeway- father of innate immunity.
16 PRRs recognize PAMPs. LPS is lipopolysacharride.
18 PRRs can be classified by location or by function.
19: complement coats microorganisms for phagocytosis. Pentraxin- C-reactive protein is a marker of acute infection. Pentraxin 3 may have role in pathogenesis of sepsis.
20: Dectin 1 senses fungi.
21: interferon induced proteins are antiviral.
nod-like receptors sense bits of broken down cell walls.
22: NOD 2 was discovered to be mutated in subset of patients with Crohn’s disease- may disrupt ability of normal flora to protect from infection.
26: Aspergillus is an opportunistic pathogen. toll negative ones died- normal ones were fine.
27: Toll receptors work completely differently in drosophila and man.
28: endotoxin is a misnomer- it is outside cell. It is lipopolysaccharide. ON surface.
Point mutation in TLR4 in mice makes them unable to respons to LPS.
29: LRR- leucine rich region. TIR (Toll/Interleukin1 Receptor) homologous domain is signalling domain.
30: TLR 11 may prevent UTIs.
31: Two groups TLRs. The ones on surface react with complement of microorganisms on surface or released into cytoplasm. Other group recognizes components in endosomes. Bacterial DNA in cell binds to TLR9. MyD88 is signalling molecule for downstream function. MyD88 is required for TLR 9 and 5. TLR4 needs at least 3 other signalling molecules. Downstream are IRAKs.
32: TLRs in Drosophila are entirely indirect.
37: Krieg worked with antisense DNAs. Cytokines were activated in his controls. CpG DNA was recognized by innate system as foreign. In humans- CpG seen less often.
40 Chloroquine blocks endosomal acidification. Inhibitory oligo also blocks (iCpG). iCpG is the only blocker for a TLR.
48: DC are dendritic cells.
53: Exaggerated inflammatory response kills in septic shock.
“cytokine storm” gets cells to site of infection.
59: Most immune defects are in adaptive immunity.
In systemic lupus, patient may make immune response to his or her own DNA complexed to histones. Leading theory of autoimmunity is that it results from aberrant immune response to an infection.

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