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Which interferons produce infected cells?
Type 1, so alpha and beta
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which effects have type 1 interferons?
- antiviral
- protein synthesis inhibition
- degradation of viral mRNA
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what are characteristics of polymorphonuclear granulocytes?
- irregular shaped
- contain granules with antimicrobial chemicals and signaling molecules
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which granulocytes are there?
- neutrophil (kills phagocytosed microbes)
- eosinophil (kills extracellular microbes)
- basophil (like mast cells, but in blood)
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What is NET?
- neutrophil extracellular traps
- release of chromosomes when neutrophils are overwhelmed by bacteria, trapping microbes extracellularily
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How kill eosinophils extracellular microbes?
They form a IgA-IgE complex, which activates degranulation. They can also be activated by complement (C5a).
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where are mast cells found?
tissue
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what do basophils and mast cells do?
promote inflammation via histamines
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which cytokines are produced by DCs and macrophages?
TNFa, IL1, IL6, IL8
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which toxins are present in a lysosome of a macrophage?
ROS and NO
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which pathways of immune activation are there?
- alternative pathway
- classical pathway
- lectine pathway
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which cytokines induce acute phase proteins?
TNFa, IL1, IL6
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Which are acute phase proteins?
- C-reactive protein
- mannose-binding lectin
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Which cytokines are produced by macrophages?
IL1, IL6, IL8, TNFa
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What can NK cells do?
- recognition of stressed or infected cells
- IFN gamma production in response to IL12 from macrophages
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Which receptor supresses NK cells?
MHC1 by removing phosphor from PTK
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Which cells do not express proper MHC1?
- virus infected cells
- tumour cells
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how do NK cells recognized stressed cells?
they upregulate MIC-a and -b
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how does inflammation work?
TNFa and IL1 upregulate E-selectin, causing leukocytes to slowly roll over the vessel surface. This will also cause the leukocyte integrin to change its conformation (high affinity), so it can firmly attach to the vessel surface and move to the site of infection
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what are PRRs?
pattern recognition receptors like TLRs (toll-like receptor), NLRs (nod-like receptor, cytosolic) and RLRs (RIG-like receptors, cytosolic)
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Name some PAMPs.
- peptidoglycan
- LPS (gram-)
- LTA (gram+)
- flagellin
- dsRNA
- bacterial DNA
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Which cells activates IFNy?
Th1
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Which cells actives IL6 & TGFb?
TH17
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Which cells actives IL4?
Th2
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Which are typical cytokines for a Th1 response?
IFNy
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Which are typical cytokines for a Th17 response?
IL17a, IL17f, IL22
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Which are typical cytokines for a Th2 response?
IL-4, IL-5, IL13
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What is recognized by TLR9?
unmethylated CpG DNA
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What is recognized by TLR5?
Flagellin
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What is recognized by TLR3?
dsRNA
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What is recognized by TLR6 & TLR2/TLR1?
- peptidoglycan
- zymosan
- LPS
- lipoprotein
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What is recognized by CD14/TLR4?
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What can C-type lectins do?
- Bind sugars Ca2+ dependent
- Bind lipids & proteins Ca2+ independent
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Name some important type 2 c-type lectins.
Dectin 1, dectin 2, DC SIGN
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How can mycobacteria suppress the immune system?
Upon high concentration, they activate CLRs which overrule the TLR activation and suppress the immune system
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What is ManLAM?
A glycolipid produced by M tuberculosis, binding to DC-SIGN and, when sufficiently present, suppressing the immune system by inducting IL-10 production even if TLR4 binds the mycobacterium.
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How can TLR4 bind LPS?
with CD14, which can bind LBP
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How can TLR2/TLR6 bind LTA?
Together with CD36
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Which TLRs act intracellular?
TLR9 (DNA) and TLR3/TLR7 (RNA)
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How is NFkB activated in the canonical pathway?
IKKs are actived by INFa, IL1, LPS or TAX; they activate p50/RELA/IkBa complex, assembling with 26S proteasome, so p50/RELA can migrate into the nucleus
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How is NFkB activated in the non-canonical pathway?
NIK is activated by CD40, LTb, BAFF or TAX, activating IKK1, causing the RELB/p100 to complex with 26S proteasome, dephosphorilating RELB/p100 so it can migrate into the nucleus
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How are genes activated?
phosphorilation of serines depending on the pathway in the cell
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What does specific gene expression depend on?
Acetylation and phosphorilation of different residues of RELA and histones
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How can certain pathogens cause IL10 production?
Activation of DC SIGN, causing phosphorilation of RAF1, which ultimately causes p50/p65 to induce IL10 production
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How can a tick cause immune suppression?
Salp15 from the saliva binds DC SIGN, and if CD4 is also activated, RAF causes MEK activation, which eventually leads to decreased TLR1/TLR2 pro inflammatory signalling
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