what are characteristics of polymorphonuclear granulocytes?
contain granules with antimicrobial chemicals and signaling molecules
which granulocytes are there?
neutrophil (kills phagocytosed microbes)
eosinophil (kills extracellular microbes)
basophil (like mast cells, but in blood)
What is NET?
neutrophil extracellular traps
release of chromosomes when neutrophils are overwhelmed by bacteria, trapping microbes extracellularily
How kill eosinophils extracellular microbes?
They form a IgA-IgE complex, which activates degranulation. They can also be activated by complement (C5a).
where are mast cells found?
what do basophils and mast cells do?
promote inflammation via histamines
which cytokines are produced by DCs and macrophages?
TNFa, IL1, IL6, IL8
which toxins are present in a lysosome of a macrophage?
ROS and NO
Name some opsonins.
which pathways of immune activation are there?
which cytokines induce acute phase proteins?
TNFa, IL1, IL6
Which are acute phase proteins?
Which cytokines are produced by macrophages?
IL1, IL6, IL8, TNFa
What can NK cells do?
recognition of stressed or infected cells
IFN gamma production in response to IL12 from macrophages
Which receptor supresses NK cells?
MHC1 by removing phosphor from PTK
Which cells do not express proper MHC1?
virus infected cells
how do NK cells recognized stressed cells?
they upregulate MIC-a and -b
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
what are PRRs?
pattern recognition receptors like TLRs (toll-like receptor), NLRs (nod-like receptor, cytosolic) and RLRs (RIG-like receptors, cytosolic)
Name some PAMPs.
Which cells activates IFNy?
Which cells actives IL6 & TGFb?
Which cells actives IL4?
Which are typical cytokines for a Th1 response?
Which are typical cytokines for a Th17 response?
IL17a, IL17f, IL22
Which are typical cytokines for a Th2 response?
IL-4, IL-5, IL13
What is recognized by TLR9?
unmethylated CpG DNA
What is recognized by TLR5?
What is recognized by TLR3?
What is recognized by TLR6 & TLR2/TLR1?
What is recognized by CD14/TLR4?
What can C-type lectins do?
Bind sugars Ca2+ dependent
Bind lipids & proteins Ca2+ independent
Name some important type 2 c-type lectins.
Dectin 1, dectin 2, DC SIGN
How can mycobacteria suppress the immune system?
Upon high concentration, they activate CLRs which overrule the TLR activation and suppress the immune system
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.
How can TLR4 bind LPS?
with CD14, which can bind LBP
How can TLR2/TLR6 bind LTA?
Together with CD36
Which TLRs act intracellular?
TLR9 (DNA) and TLR3/TLR7 (RNA)
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
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
How are genes activated?
phosphorilation of serines depending on the pathway in the cell
What does specific gene expression depend on?
Acetylation and phosphorilation of different residues of RELA and histones
How can certain pathogens cause IL10 production?
Activation of DC SIGN, causing phosphorilation of RAF1, which ultimately causes p50/p65 to induce IL10 production
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