-
Three tiers of
defense
- Mechanical Barriers:
- · Skin,
- Mucous Membrane (protection of organs against MO, create environ. where things
- don’t cross readily
- · Chemical Barriers: Saliva,
- Tears (dilute toxins and remove from body)
- Inflammation
- · Without inflammation: Cannot heal any
- wound sustained/or clean up and rid the MO
Immunity
o B Cell, T Cells responses is specific immunity
o Defense is specific to the MO (invader)
o And have defense for future also
-
Cardinal
Signs of Inflammation
- · Redness,
- Heat, Pain, Swelling at site of injury
- o Redness:
- Due to vessel dilation and increased blood flow
- o Heat:
- Due to vessel dilation and increased blood flow
- o Swelling:
- Increase Pressure (Fluids, Proteins,
- Cells, leave the blood and goes to the site of injury)
- o Pain:
- increase blood flow/swelling cause pain
- because substances that are released irritate the nerve endings
-
What are the
local changes that will occur because of inflammation?
- · Increase
- blood flow at the site: (hyperemia) redness at site
- o Mediators
- (cell or plasma derived) go to the site of injury and recruit other
- cells/proteins to have inflammatory response.
- · Increase
- capillary membrane permeability
- o Make
- WBC/proteins/etc that do not want to cross membrane want to cross the
- membrane.
- · Diapedesis
- of WBC from the blood to the site of injury
- o Movement
- of WBC due to built in mechanism
- · Walling
- off Effect of Inflammation
- o Create
- mesh work and ID where the site of injury is and put a gate around that area
- o Only
- want certain things to take place in that gated area so we can clean up the
- debris, MO, and prepare it optimally to initiate wound healing and repair
- mechanism
-
Plasma derived mediators
- § IMP
- for the removal of MO from SOI/clean up
- § Principle
- player is bradykinin
- ú Participates
- with vasodilatation at the SOI
- ú Serves
- to facilitate the sensations of pain
- · Bradykinin
- will irritate the nerve endings to cause pain.
- § Clotting:
- trying to create the mesh work around the SOI
- § Not
- trying to increase the blood flow to the entire body but only that SOI
- § Trying
- to create a clot to highlight the vasodilatation at that SOI by restrict blood
- from moving in and out that area so we maximum the movement of substance out of
- the blood to the SOI
- § Opposite
- to coagulation system
- § Anti-
- coagulation: increase the blood flow, and increase the deliver of the mediators
- for the pro-inflammatory response to the SOI
-
Cell derived
mediators:
- · Mediators
- comes from cells
- o Prepackaged
- (ready for release)
- o Needs
- to be synthesized and then released
-
Acute
Inflammation
Immediate Effect
Knife cut:
- o First,
- increase in blood flow
- § Increase
- in H from mast cells, Bradykinin released which promotes vasodilatation at SOI
- (not whole body)
- § And
- vasoconstriction at the periphery of the injury
o Histamines:
- § Endothelial
- cells constricts and thus produces gaps/holes in vessels walls
- § The
- junctions aren’t as tight as they used to be so substances in blood can move
- through these holes to the SOI
- § Increase
- in permeability: fluids proteins, etc leave blood and goes to site of injury
- ú Acute,
- because once fx is done, the substances leave back to the blood
-
Diapedesis
(aka extravasation)
- Movement
- of WBC from blood to tissue
- · As
- a result of the H being released, the jx are relaxed and have promotion of the
- expression of receptors
- · Receptors
- called p-selectin pops up on the surface
- of the endothelium and interact with the proteins that are always expressed on
- the surface of a Neutrophil.
- · Neutrophils want to stay in the blood,
- but we need these neutrophils to go to SOI, so the neutrophil will capture the
- receptor and cause the movement out of the blood through the relaxed jx and
- into the SOI.
- · Macrophages:
- phagocytes (clean up the debris and IDing bacteria. that are tagged for
- destruction)
-
Time Course
Chart
- § Very
- large amounts of neutrophils present in the first 4 to 6 hours after
- injury
- § After
- 4-6 hours: your body is now starting the clean up the injury
- § Takes
- care of the situation acutely
- o recruit
- more macrophages
- § local
- macrophages that causes more neutrophils to go to SOI
- o Monocytes:
- immature macrophages
- § Take
- a while to get to the SOI
- § Once
- at the site, they will mature and become macrophages and perform the fx
- § More
- prolonged progression of immature/mature macrophages over (18 to 24 hours peak)
- § Diminishes
- out after 48 hours
- · After
- 24 hours: increase in T lymphocytes
-
Leukocyte
Adhesion Deficiency
- · No
- P-selectin receptors on surface the
- endothelial cells
- o Neutrophils
- can’t target the area, so no WBC can get to the SOI to take care of injury or
- MO
- · Disease
- in children that have recurrent bacterial infection because you don’t get rid
- of the MO from the primary invasions because can’t get the WBC there to take
- care of the MO.
-
Lines of Defense
- · 1st:
- localized macrophages (mins) by chance they are present during the injury.
- chemical mediators and plasma derived mediators that promote localized
- macrophages to be 1st line of defense
- · 2nd:
- localized macrophages triggers/attracts further mediators to attract more
- macrophages to the SOI
- · Chemotaxis:
- movement of cells to that attractive environment by chemical presence
- · 3rd:
- prolonged monocytes: immature/mature macrophages goes to SOI after 18 hours
- · more
- macrophages to prepare site for wound healing and repair
-
Complement system:
- : target MO for removal and
- destruction
-
o Clotting/
coagulating system and Fibrinolytic system
- § Decrease
- or increase blood supply depending need
-
-
Systemic Changes during
inflammation
- · When
- sustain injury or MO invasion, can produce systemic changes
- · Changes
- that occurs to assist us in controlling the MO invasion or to prepare body to
- rid the invader
· Fever
- · General
- Malaise (sleepy) – shutting our system down a little bit, allow body to rest so
- give chance for responses to occur locally or globally around body
- · Decrease
- own activity to allow body to response accordingly
- · Appetite
- suppression, pain, pulse rate are the effects of bradykinin
-
Diagnostic Test
- · Neutrophil
- count in peripheral blood (painful and long)
- · Increate
- erythrocyte (RBC) sedimentation rate (ESR):
- o Blood
- sample and spun/center fuse it down into a medium
- o Goes
- to a certain level and stays there
- o You
- will see an increase in fibrin and cause RBC to clump together and it will spin
- at a different level. Increase ESR means inflammatory event
- · Increase
- acute phase proteins in the blood
- o Proteins
- that aren’t usually in the blood, but because of the inflammatory event, you
- see the presence of these proteins
- § Ex.
- C- reactive proteins most common, made in liver and it usually tags bacteria
- cells/ injured cells for destruction
-
Benefits of
Inflammation
· Fever
- o Increase
- body temperature to create an unfavorable environment for MO to grow.
- o Stimulates
- an immune response (specificity assigned to the invaders)
- · Clots
- (walling-off effects)
- o Occurs
- to seal off the injury/MO and don’t let it spread to rest of body
- · Clean
- up area up to return to normal fx, extra fluids dilutes toxins and chemicals
- also
-
Review on Fever
- · Release
- of pyrogens in circulations
- · Resets
- and increase in the set point
- · Results:
- body conserves heat
- · Increased
- in body temperature
- · Body
- response: warm, sweaty, lethargy
- · To
- combat the MO to grow further
- · Once
- the MO gone, can return back to normal
-
Chronic
Inflammatory Disease
· Not just a prolonged local acute inflammation
- o Ex.
- Mouse is not a small rat
- · Area
- of body in which mechanism is activated and it just stays on
- · Constantly
- have exposure to the certain organs to mediators that promote inflammation
- § Inflammation
- of body organs that compromise it’s fx
- · Inflammatory
- response that is prolonged
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