INFLAMMATION INFORMATION -Chronic Low Level Inflammation
Inflammation - Can't Live
with it, Can't live without it!
Inflammation Information
Inflammation is a response to injured tissue
- by pathogens (E.g. bacteria,
viruses, fungi, parasites), toxins/chemicals (E.g. air particulates), physical injury, burns,
or by an overzealous immune system.
Without inflammation, infections (incl. bacterial, viral, fungal and
parasitic) would go unchecked and wounds (E.g.trauma,
surgery, burns, damage inflicted by a saber tooth tiger!) would never heal
When you "catch" a cold
(actually a viral infection) your throat becomes
sore, your eyes water, and your sinuses are congested -
These are the physical signs of inflammation as fluid and cells build up, as a
result of the immune system's fight against a hostile invader.
Inflammation is characterized by increased blood
flow to the tissue causing:
✔ Increased temperature
✔ Redness
✔ Swelling - as
blood vessels leak fluid into surrounding tissues - a process that helps isolate
any foreign substance.
✔ Pain
Mast cells are key players in initiating
inflammatory process
- Found in tissues
- Their surface is coated
with a variety of receptors - which, when engaged by the appropriate
ligand (E.g. LPS/Endotoxin of Gram-negative
bacteria, peptodoglycan of Gram-positive
bacteria), trigger release of granules (by exocytosis), some discharging their
inflammatory mediators immediately, others later.
- Mast cell cytoplasm
is loaded with granules containing potent mediators of inflammation
- dozens of
these are released when stimulated by the immune system, which
recruit all types of white blood cells to the site, many of which
are activated to produce their own inflammatory mediators.
• Monocytes - that
become macrophages (“big eaters”) when they leave the blood and enter the tissue
• Neutrophils - squeeze through capillary walls and into infected tissue to kill invaders and
then engulf the remnants by phagocytosis;
• Antigen-presenting dendritic cells-
whose main function is to process antigen material and present it on the
cell
surface
to the immune system's T-cells,
thereby acting as messengers between the innate and the adaptive immune
systems).
• All kinds of lymphocytes:
Natural Killer (NK) cells -specialized to kill certain types of target cells (esp.
virally infected or cancerous host cells) in innate (1st line of
defense) immunity
•
Eosinophils -blood levels increase sharply with parasitic worm infections. Eosinophils
release the cytoxic contents of their granules on the invader.
Some of the better known inflammatory mediators
released by mast cells
(which initiate inflammation or deal with the damage)
- Histamine
✔ Released from mast cell granules in nearby
connective tissues
✔ Increases blood flow to the area and the
leakage of fluid, pathogen-fighting WBCs and proteins from the blood into the
tissue space
✔ Produces redness, warmth and swelling
- Bradykinin
✔ Produced from an inactive precursor always
circulating in the blood
✔ Dilates blood vessels /lowers blood pressure
(by stimulating NITRIC OXIDE), and
increases blood vessel permeability -to allow needed blood components
to enter the tissue space; ACE inhibitor drugs reduce blood pressure by
increasing bradykinin
✔ Contracts airway smooth muscle, is a
potent bronchial vasodilator, stimulates mucus secretion and coughing -
bradykinin activates release of neuropeptides from sensory nerves in airways,
leading to reflex bronchoconstriction, coughing and neurogenic inflammation
Fuller RW, Dixon
CM, Cuss
FM, Barnes
PJ. Bradykinin-induced bronchoconstriction in humans. Mode of action.
Am Rev Respir Dis. 1987 Jan;135(1):176-80.
PubMed
✔ Like histamine, effects produce redness,
warmth and swelling
✔ Involved in pain mechanism
✔ Stimulates phospholipase -
to increase the production of prostaglandins
(local “hormones”)
- Prostaglandins, Leukotrienes
✔ Potent mediators of inflammation -these
hormone-like messengers are derived from specific dietaryessential fats (EFAs)
in local cell membrane phospholipids.
Consuming a balance of both inflammatory (most omega-6
fats) and anti-inflammatory
(omega-3 EPA and DHA, and
omega-6 GLA) fatty acids will
ensure a balanced response when dealing with injured tissue;
✔ All inflammatory cells have receptors for TNF-α and are activated by
it to synthesize more on their own -
This positive feedback quickly amplifies the
response.
✔ Produced by activated phagocytes:
macrophages and neutrophils
✔ Toxic to microorganisms, but can also lead
to tissue injury
- Interleukin-1
(IL-1)
✔ This cytokine is released by macrophages,
monocytes and activated platelets
✔ Has paracrine effects on cells in the
local vicinity:
▪ Causes cells to
produce tissue factor to trigger blood clotting;
▪ Stimulates
synthesis/secretion of other interleukins
▪ Helps activate
T-cells in the adaptive (2nd line of defense) immune response;
✔ Has endocrine
(hormonal) effects via the blood:
▪ Decreases blood
pressure
▪ Induces fever
(stimulates prostaglandinrelease,
which affect hypothalamic temperature control);
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