Inflammation Information - Can't Live with it, Can't live without it!

About Inflammation

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 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

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

–   Mast cell cytoplasm is loaded with granules containing potent mediators of inflammation

–   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.

–   Dozens of potent mediators are released - which recruit all types of white blood cells to the site. Many of these recuited WBC's 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 (1^st line of defense) immunity

~B-cells and T-cells - leading to an adaptive immune response (2^nd line of defense);

• 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 - 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 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;

✔ 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 dietary essential 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;

EFAs -▲  Local Hormones –First Response Team

–   Tumor Necrosis Factor-alpha (TNF-α)

✔ Large amounts released by stimulated mast cells

✔ TNF-αused to regulate immune cells - to induce fever, apotosis (natural cell death), sepsis (via IL1 & IL6 production), cachexia, inflammation and to inhibit tumorigenesis and viral replication

✔ All inflammatory cells have receptors for TNF-αand are activated by it to synthesize more on their own - This positive feedback quickly amplifies the response.

–   Reactive Oxygen Species (ROS)

✔ 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

✔ Its 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;

✔ Its endocrine (hormonal)effects via the blood:

▪Decreases blood pressure

▪Induces fever (stimulates prostaglandinrelease, which affect hypothalamic temperature control);