Response A review The 3 Lines of Defense FIRST line Barrier protection nonspecific treats each pathogen the same acts to prevent the pathogen from getting into the body skin mucous membranes tears sweat ID: 617052
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Slide1
The Inflammatory Response
A reviewSlide2
The 3 Lines of DefenseFIRST line: Barrier protectionnon-specific (treats
each pathogen the
same)
acts to prevent the pathogen from getting into the body
skin, mucous membranes, tears, sweat
SECOND line: Acts to destroy/inactivate a pathogen if it breaks the barriers of the first line
non-specific -phagocytic leukocytes
neutrophils and macrophages
THIRD line: Acts to destroy specific pathogens that are not destroyed/inactivated by the second line
specific
Lymphocytes
T cells, B cellsSlide3
The Inflammatory Response Part of the second line of defenseThe pathogen has gotten through the barrier protections and is in the tissues.Slide4
Uh…oh!Splinter!!!!Slide5
What’s happening?Splinter (or pin) has broken through the barrier, carrying bacteria into the tissue.
Mast cells release histamine.
Macrophages that are in the tissue secrete chemical signals (cytokines) causes
nearby
capillaries
to
dilate and makes
them more permeable (leaky
).Slide6
What’s happening?
Histamine released from mast cells cause more macrophages to enter from the blood stream.
Cytokines released from macrophages increase the blood flow to the site and “call” more neutrophils and antimicrobial peptides to the site.
now arrive and pass through the leaky capillaries into the tissue
ingest and kill the invader by phagocytosis and then fusion w/lysosomes
More blood
redness, increase in temp,
fluid leaks from the vessel into the tissue
swellingSlide7
What’s happening?Neutrophils continue to digest the bacteria and cell debris.
Inflammation
subsides
and tissue begins to heal.Slide8
Hooray for the Inflammatory Response!!!The Inflammatory Response is a GOOD thing, because it:Prevents the spread of infection.
Helps remove pathogens and damaged tissues.Slide9
But….there’s a dark sideW
hat if the inflammatory response of the immune system is
continually
stimulated?
…too much of a good thing
For example, there can be different types of stimulants:
1)Infectious: unresolved viral or bacterial infection
2)Noninfectious: pollen
, smoking, autoimmune reaction,
obesity
and tissue
damage
from wounds, tumors,
heart
disease,
atherosclerosis and
autoimmune
disease
This can lead to…Slide10
Chronic InflammationSlide11
Chronic Inflammation is NOT
a good thing:
CI can lead to:
Development
of Type 2 diabetes, exacerbation of heart, liver
and
kidney disease, Alzheimer’s, some cancers (perhaps from
increased
mutational rate and enhanced angiogenesis), fibrosisSlide12
What’s the difference between Acute Inflammation and Chronic inflammation?
Acute inflammation:
the normal Inflammatory response
●neutrophils dominate.
●
you
feel and see it (pain, redness, swelling, heat).
●
Inflammatory
cytokines are expressed and do their job and
resolution occurs relatively quickly –it’s over and done with.
Chronic inflammation (CI):
● macrophages dominate.
●
T
cells and B cells become involved.
●CI is
silent
—progresses without one even knowing it’s happening
●
Persistent
, increased expression of inflammatory
cytokines.Slide13
What are these cytokines?A trio of 3 proinflammatory cytokines always predominates.
IL-1 (
interleukin
-1)
IL-6
(
interleukin
-6)
TNF-
α
(
tumor necrosis factor-alpha)Slide14
What happens because of these cytokines?
●
IL-1
stimulated very early by macrophages
increases the permeability of capillaries
calls more neutrophils to the tissue
●IL-6
secreted by T cells and macrophages
stimulates the inflammatory response
increases the production of neutrophils in the bone marrow
●
TNF-
α
activates macrophages
increases permeability of capillariesSlide15
So secretion of these cytokines just continues the inflammatory processSlide16
ReminderWhy are we concerned about chronic inflammation?
Recent studies have suggested that the constant secretion of these cytokines and stimulation of the inflammatory response can lead to….
Type 2 diabetes
Exacerbation of heart, liver and kidney disease
Alzheimer’s disease
Fibrosis of some tissues
Some cancersSlide17
HOW?????Let’s briefly review how cells communicate with each other
cell-signalingSlide18
Three stages of Cell Signaling
RECEPTION
a signaling molecule binds to a SPECIFIC receptor protein
molecule
TRANSDUCTION
This
causes the receptor protein to change shape. Now the signal is changed into another form that the cell can recognize that will cause it to respond in a specific way.
This may occur in multiple steps called a
CASCADE.
RESPONSE
The cell responds in a specific
way and maybe
the production of a particular
protein.Slide19
Reminder:Causes of chronic inflammation can be infectious or non-infectious
I
nfectious
: such as an unresolved viral or microbial infection, which
results
in
continual
immune stimulation
Example: Periodontitis from persistent dental infections
HOW?? -there is a constant source of bacteria –the immune system is constantly being required to try to rid the body of these bacteria
constant inflammationSlide20
Non infectious causespollen, smoking, pollution, autoimmune reaction and tissue damage
from wounds that don’t heal,
tumors, heart disease and atherosclerosis
…… and……obesity!
Pollen and particles from smoking and pollution can constantly irritate certain tissues
Tissue damage from atherosclerosis, heart disease and wounds that don’t heal can constantly irritate certain tissues, as well.Slide21
Huh?…OBESITY??? How can having too many adipocytes (fat cells) lead to a state of chronic inflammation?
1) Adipocytes can secrete IL-6
..but that’s not the end of the story…..
2) excess
free fatty acids
bind
to receptors
on the adipocytes
3) cell signaling now leads to
increase
of the release of IL-6Slide22
So what can happen now? IL-6 then binds to receptors on the pancreatic beta cell ……..
this
prevents the cell from getting the signal to make
insulin
Result????Slide23
Type 2 Diabetes!Slide24
If CI is “silent”, but dangerous, is there a way for someone to know if it’s happening in their body?
Reminder: Inflammatory markers:
1) IL-6
2) IL-1
3) TNF-
α
CI can be determined by measuring one of the inflammatory markers in a sample of their blood.Slide25
THE ELISA
We can determine if too much of the protein IL-6 is in someone’s blood by doing a laboratory test called an ELISA