Lecture 4 - Innate Immune Recognition Flashcards
what are the 3 different pathways of complement activation?
classical, alternative, lectin
Which key effector complement protein is generated by all 3 activation pathways?
c3 covertase
what is the role of the membrane attack complex?
create pores
In addition to MAC formation, name 2 other terminal outcomes of complement activation
1 - recruitment of inflammatory cells
2 - opsonization
name one clinical consequence of C3 deficiency in Brittany Spaniels
renal disease
What are Pathogen-Associated Molecular Patterns (PAMPs)
common features on pathogens that are absent in host tissues
How are PAMPs like Hogwarts houses
they are common traits like the defining factors of sorting (bravery, wisdom, etc.)
what PAMP does gram-negative bacteria have
a. peptidoglycans
b. lipopolysaccharide
c. dsRNA
d. mannan
b. lipopolysaccharide
what PAMP does gram-positive bacteria have
a. peptidoglycans
b. lipopolysaccharide
c. dsRNA
d. mannan
a. peptidoglycans
what PAMP do viruses have
a. peptidoglycans
b. lipopolysaccharide
c. dsRNA
d. mannan
c. dsRNA
What are the 3 types of signaling type PRRs
1 - Toll-like
2 - Nod-like
3 - RIG-1-like
which signaling PRR is found on the membrane
toll-like
what is the common product of all signaling PRR pathways
NF-kB
What is the result of PRR signaling
activation of transcription genes (adhesion, inflammation, etc.)
Toll-Like Receptors (TLRs)
plasma (4/5) recognizes wall components and the endosomal membrane recognizes DNA
what does TLR5 recognize
flagellin
where is TLR4 and TLR5 present? what is the clinical significance?
present on the basolateral surface, only bacteria that have bypassed the rest of the cell’s defenses should trigger
NOD-like receptors
within cytosol, recognizes peptidoglycan
RIG-1-like receptors
within cytosol, recognizes dsRNA and ssRNA, leads to expression of anti-viral responses
which of the following is NOT a characteristic of PAMPs
a. essential to microbes
b. common in microbes
c. abundantly produced
d. present in host tissues
d. present in host tissues
viruses in endosomes are recognized by
TLRs
what do the signaling PRRs all have in common
a. location
b. cell type
c. activation of NF-kB
d. what they recognize
c. activation of NF-kB
what do phagocytotic receptors do and give examples
trigger phagocytosis by binding to pathogenic components (complement receptors, FcyR, mannose)
T/F: opsonization is more efficient phagocytosis than through PRRs alone
True
what recognizes IgG (immunoglobulins)
FcyR
what are the 4 steps of phagocytosis
1 - recognition/attachment
2 - engulfment
3 - phagosome-lysosome fusion
4 - Destruction
How are phagosomes created
involution of the plasma membrane with a microbe attached after cytoskeletal arrangement PRRs triggered
what 3 ways do phagosomes kill pathogens
1 - pH becomes acidic
2 - fusion with lysosomes (phagolysosome)
3 - oxidative burst (generate reactive oxygen species)
superoxide anion is produced by
NADPH oxidase
O2. reacts with H+ and H20 to form
hydrogen peroxide
hydrogen peroxide is further converted to
hydroxyl radical (.OH)
Neutrophils have ____ that convert hydrogen peroxide to ____
myeloperoxidase; ClO- (active bleach)
what converts arginine to nitric oxide (NO)
nitric oxide synthase
NO + O2. = _____
peroxynitrite
T/F: the free radicals are NOT damaging to components within the phagosome
False - damages lipids, DNA, and protein
which of the following recognizes IgG bound to microbes
a. FcyR
b. Toll-like receptor
c. mannose receptor
d. complement receptor
a. FcyR
which of the following phagosomal enzymes is not in macrophages
a. iNOS
b. hydrolase
c. NADPH oxidase
d. myeloperoxidase
d. myeloperoxidase
If there is a cellular injury, how does the immune system respond
release cytosolic/nuclear proteins and metabolites
If there is a tissue injury how does the immune system respond
production of extracellular matrix components
What Harry Potter character is the immune system response to self-damage most like
Wormtail - acts as a double agent; the immune system needs to know not
only non-self but when self has gone bad.
Where do extracellular DAMPs come from
the connective tissue
what creates inflammasome to cleave the pro-form of pro-IL so they can translocate
DAMPs
DAMPs
Damage-Associated Molecular Patterns
What Harry Potter character is the PAMP and DAMp combined system like
Horcruxes - both must be active for inflammation to occur
All are major functions/results of phagocytic receptor engagement EXCEPT
a. adherence
b. Engulfment
c. NF-kB activation
d. phagosome formation
c. NF-kB activation
PAMPs and DAMPs must work TOGETHER to coordinate which of the following responses
a. engulfment
b. inflammasome production
c. phagosomal-lysosomal fusion
d. IL-1B production and activation
d. IL-1B production (PAMPs) and activation (DAMPs)
Ligand binding to signaling PRRs results in activation of _____
NF-kB or IRF
Signaling through PRRs leads to
1 - cell activation
2 - inflammatory cytokines
3 - adhesion molecules
4 - arachidonic acid cascade
5 - recruitment of leukocytes
Neutrophil Extracellular Traps (NETs) respond to
cytokines and PAMPs
Natural Killer cells recognize cells via 2 types of receptors. what are they?
Activation receptor (viral proteins)
Inhibitory receptor (MHC on self cells)
Perforin
inserts into the membrane
granzyme enters the perforin pore to
trigger apoptosis
What is the INHIBITORY trigger for NK cells
MHC class 1
How do NK cells kill their target cells
perforins and granzymes
treatments that block IL-1 may have this consequence
more infections
why do we treat systemic lupus with quinine compounds
to prevent endosomal acidification needed for TLR signaling
what is frustrated phagocytosis
a pathogen is too big for a macrophage to engulf and will release granules to help pre-digest that may cause damage to host cells of ECM
