Inflammation 4 Flashcards
in add’n to opsinins coating phagocytes, the neutrophil can also be triggered to engulf pathogens by
PAMPs on pathogens bindnig to PRR
CR3 and CR4 are
complement receptors
CR3 and CR4 bind to
C3B
IC3B
neutrophils have two types of granules
auzorophilic granules
specific granules
contained in the granules are
microbial substances
following delivery of the granules from neutrophils to phagosome we also get delivery of
lysosomal contents to phagosome
when lysosomes fuse with phagosome forms
phagolysosome
neutrophil after phagocytosis does what
dies - it exhausts itself
if infection isn’t resolved by neutrophils the
monocyte → macrophage and cleans up after neutrophil
part of specific granuels for killing in neutrophils is what coplex
NADPH oxidase complex
superoxide is reactive and can do what
damage to biomoleuless
superoxide dismutase converts 2O2- to
hydrogen peroxide
hydrogen peroxide converted by myeloperoxidase into:
HOCl (bleach!)
oxidative killing increases O2 demand by 100x so it’s called
respiratory burst
do resting neutrophils have NADPH complex
no they aren’t active in terms of oxidative killing
what are the non-oxidative killing list of neutrophils
Elastase
Cathepsins/other proteinases
Collagenase
Lactoferrin
“Cathy Elatedly Lactated in Collage”
which is most important killing mechanism for neutrophils
oxidative killing
in individuals without ability to form NADPH disease:
they are totally competent in non-oxidative killing mechansm
they have recurrent bacterial infections
memorize table on pg
87
monocyte differentiate into what in tissue
macrophage
how do monocyte get into infected tissue
same way as neutrophil
rolling
tight binding
pulled through gaps
monocytes and macroh[ages have what on surface
PRR - allows them to take up opsinized material and the bacteria or other pathogens that have glycoproteins on surface
receptors on surface of macrophage we need to know
pg 90 memorize
Mac-1, CD11b/CD18
pg 90
Dectin-1
allows fungi to be recognized and taken up - it binds to beta glucans (part of fungal cell wall)
macrophage has how many TLR
10 - can detect variety of pathogens
what is first to infiltrate infection
neutrophil
neutrophils are mobilized from
bone marrow
neutrophils once they do their job they will
die
the cell following neutrophil will
continue fighting or clean up dead neutrophils
monocyte → macrophage
cytokines that promote inflammation
IL-1, IL-6, IL-8, IL-12, Interferons, TNFs (TNF-)
IL12 and interferons are important in what response
innate respose against viral infections
once inflammatory response has done its job need what
IL-10 and TGF-β
IL-10 and TGF-β are
anti-inflammatory
IL-1, IL-6, TNF-a control
acute phase response
IL-1, IL-6, TNF-a iportant for promoting
acute phaseinflammation
interferons do qhat
Activate NK cells.
Provide anti-viral protection to neighboring cells.
IL is a
cytokine
IL-1 induces expression of
adhesion molecules on vascular endothelial cells
TNF alpha
shares with IL - 1 increases expression of adhesion molecules on vascular endothelial cells
allows recuirted leukocytes to roll on endothelial cells and halt when integrin has been activated by exposre of leukocyte to chemoattractant
induces production of acute phase protiens
induces sytokine secretion by inflammatory cells
Tumor Necrosis Factor-alph is
TNF alpha
TNF alpha important for controling
localized infection
systemic release of infection thats bad why
system production of TNF alpha will cause bulk movement of fluid from circulation into tissues
will lead to dramatic drop in blood pressure, collapse of blood vessels, which leads to disseminated intravascular coagulation which leads to oran failure
Disseminated intravascular coagulation leads to
organ failure
release of gram negative through body can lead to
septic shock/death
IL-8 signals thorugh
g proteins
IL-8 acitvates
integrin to allow leukocyte to pull itself into tissues
anti-inflammatory cytokines
IL-10
Transforming Growth Factor- (TGF-)
chronic inflammation happens if
infection persists
autoimune disease
response to undigestible foreign material
hallmark of chronic inflammtion is activation of
t cells
activation of t cells promotes activation of
marophages
once t cells activated they attract more
monocytes and activate monocytes once they differente to mcrophages via cytokine IFN-gamma
neutrophils are secreted adn their activity associated with
TNF-alpha (secreted by T cells)
CD4 T cell subset aquired for cell mediated immune resposes
Th1
Th1 upregulate
Cytokines from a type of CD4 T cell called Th1 cells upregulate the intracellular killing ability of macrophages and promote the differentiation and activation of Cytotoxic T cells.
Activated T cells make
IFN - gamma
CD40 ligand
CXCL2
CD40 ligand will bind to
CD40 on what cel is interacting with
IFN gamma and CD40 together activates
activates macrophages to destroy what they have taken up
CXCL2 cause
macrophages to accumulate at site of infection
granuloma
structure our immune system uses to wall off bacteria that we cannot eliminate - like microbacteria
interaction b/w th1 cells and macrophages result in formation of
granuloma
formation of granuloma takes
weeks to months
describe granuloma
fuse together and form syncitia (multinucleated giant cells)
bacteria trapped in it
what is doinant cell in granuloma
macrophages
tiny layer of t cells surrounding it
dominant effector cells in acute inflammation
neutrophils
dominant effector cells in chronic inflammation
Macrophages
Th1
innate response against viruses, who is very important in it
type I IFNs
type I IFN does what
primes adj cells to be much less suscpt. to promoting virus replication
induce PKR and RNase L
Type I IFNs increase expression of
MHC class I enhance the ability of affected cell to show that it is infected
APC
cytotxoci t cells need what to recognize virally infected cell
MHC class I
APC stands for
antigen presenting cell
draw chart of induction of antiviral state
pg 108
viral genome is coactivator for
oligoadentylate synthase - this will then activate RNase L
during innate response of viral infection what is first thing you will see
innate cytokines being produced
type I interferon
IL-12
in vast majority of cases the innate response is not able to
eliminate infection
look at graph of virus titer with viral infection
pg 109
NK cells have ability to
kill cells infected w/ certain viruses
type II interferon
IFN gamma
production of type II interferon is restricted to which cells
NK and T cells
production of type I interferon by which cells
almost all cells
IFN gamma promotes
killing by macrophages
pdoruction of antiviral agents by uninfected cells (RNase L, etc)
IFN I and II increase expression of
MHC I
IFN II increase expression of q
MHC II
type II interferen signals through
jak stat pathway
how do NK cells know what to kil
ldon’t have antigen specific receptors
have KAR receptor
what does KAR stand for
KAR=Killing Activating Receptor
if both inhibitory receptor and activating receptor are bound then NK cell wil not
kill cell it is interacting with
ligand for inhibitor receptor
KIR
certain viruses and tumors have properyt that they downregulate expression of
MHC class 1
when viruses and stuff remove MHC class I then negative signal
dominantes
receptors that transmit activating signals have in their cytoplasmic tails a sequence known as
ITAM
activating receptors have
ITAM
inhibiting receptors hav
ITIMs
ligand for activating receptor tend to be molecules expressed on surface when cell is stressed, what family
MIC A
MIC B
when cell is stressed is expresses what
MIC A
MIC B
MIC A or MIC B acitvate
NK cells
NK cells kill cells using same mechanism as
cytotoxic t cells
how to NK cells kill
- Granule release:
Perforins and associated molecules (form pores in target cell)
Granzymes (proteinases that enter through pores) attack interior of target cell initiating changes leading to apoptosis
Induction of apoptosis via FasL/Fas (CD95L/CD95) Fas ligand (FasL) on NK cell engages Fas on target cells and induces apoptosis.
CD95 is
Fas
CD95L is
FasL
why is granule release more important than induction via FasL/Fas (killin by NK)
it’s faster
how does granule release work
perforin forms pores
granzymes enter through pores and inititae apoptosis
FasL binds to Fas to induce
apoptosis in cell that expresses Fas
killer cell is cell that expresses
FasL
almost every cellin body will express Fas?
yes
draw out killing mechanisms for NK
pg 119
bacteria and fungi what are prominent players
neutrophils and macrophages
virus - what are prominent players
predominantly interferons and Natural Killer cells
for paraiste what are prominent players
Predominantly mast cells, basophils and eosinophils
what induces the killing of NK cells
IFN alpha
IFN beta
IL-12
If there is no dominant negative signal what will NK cells do
kill it!
