Lecture 4: inflammation and inflammatory mediators Flashcards
Acute inflammation is
A protective response
Innate immunity
Often, but NOT always, ,caused by infection
Trauma
Classic signs of inflammation
Pain
Redness
Immobility
Swelling
Heat
triggers of inflammation
Pathogens
Damaged tissue
Both pathogens and damaged tissue contain molecules that bind to pattern recognition receptors on complement and sentinel cells
The sentinel cells are:
Macrophages
Dendritic macrophages
Mast cells
Mechanisms of inflammation
Sentinel cells produce a variety of mediators
Vasodilation
Increased capillary permeability
Increased sensitivity to pain
Initially the predominant inflammatory cell is the neutrophil
Sentinel cells do what in inflammation
Sentinel cells produce a variety of mediators.
Promote blood flow
Attract cells, particularly PMNs
Improve phagocytosis
Vasodilation is caused by what in inflammation
Histamine and prostaglandins are released by macrophages, mast cells and neutrophils.
Increased blood flow
Which signs?
Redness and heat
Increased capillary permeability is caused by what in inflammation
Histamine and prostaglandins
Exudation of fluid
Which sign?
Swelling
The neutrophil does what for inflammation
Attracted by mediators from activated complement and sentinel cells.
Attach to the endothelium of capillaries.
Crawl out (diapedesis)
Neutrophils have a short life.
Pus is the fluid formed by many dead neutrophils, cells and bacteria
Inflammation is further activated by
Binding pathogens or damaged tissue at their pattern recognition receptors
Products of activated complement
Inflammation is stimulated to
Phagocytose
Kill ingested material.
Activation of clotting
Proteins in the exudate include:
Clotting factors
Fibrinogen
Clotting activated by damaged, leaky tissue.
Fibrin is formed
Acts as a net to trap pathogens.
May form a capsule around the site of inflammation.
Abscess = pus trapped in capsule
Chronic inflammation is caused by
Neutrophils decrease
Macrophages and lymphocytes dominate in tissue.
Numbers in blood can increase.
Fibrous tissue is produced.
Healing is initiated by
Insult is removed by phagocytosis and killing.
Inflammatory mediator production and inflammation stops!
Damaged tissue replaced by
New tissue
Fibrous tissue (scarring)
The systemic response of inflammation in moderate and severe cases
In moderate and severe inflammation there is a whole-body response
Especially likely in bacterial/viral infections
Blood neutrophils do what in inflammation
In very severe inflammation the number of neutrophils in the blood may initially decrease as they move to the site of inflammation
Bone marrow increases production in response to inflammation.
PMN count in blood increases.
The usual response to moderate inflammation
Mild inflammation does not produce a change in the blood count.
Fever is caused by and does what
Interleukins (IL) and tumor necrosis factor (endogenous pyrogen) is released from sentinel cells.
Act on the hypothalamus.
Prostaglandin mediated.
Increases the ‘set point’.
Shivering, huddling, raised hair coat
Directly inhibits growth of some pathogens.
Also enhances the activity of neutrophils, macrophages and T-lymphocytes
Systemic response to inflammation
Removal of trace nutrients from blood
Especially blood
Low iron and fever can work together.
Reduced appetite
Breakdown of muscle to fuel body
Potentially harmful if prolonged
Potentially harmful if prolonged
Liver does what
Liver is stimulated to produce proteins.
Acute phase reaction proteins
Proteins that are necessary for, and part of, local inflammatory response
Soluble pattern recognition receptors, complement components, clotting molecules, and iron binding proteins.
Part of the clotting system
Fibrinogen, prothrombin
This is why fibrinogen is measured on CBCs in large animals.
Acute phase proteins are
Liver is stimulated to produce proteins.
Part of clotting system
Remove iron (ferritin, ceruloplasmin)
Some complement system proteins (Lectin pathway)
Opsonize microbes
Recruit immune cells to inflammatory site.
Proteins that help degrade inflammatory products.
Plasminogen breaks down blood clots
Downregulate (control) inflammation.
Negative acute phase proteins are
Levels of these proteins decrease with inflammation.
The most important are:
Albumin provides source of aa
Transferrin transfers iron
Common methods for controlling inflammation
Cold water
The early stages of some types of inflammation
Stops destructive enzymes.
Laminitis (have them stand in ice water buckets)
Antihistamines
Diphenhydramine (Benadryl)
Cetirizine (Reactine, Zyrtec)
Particularly effective in allergic inflammation
NSAIDs
Non-Steroidal Anti-Inflammatory Drugs
Block synthesis of some/all
Prostaglandins
Thromboxanes
Examples
Flunixin (Banamine)
Carprofen (Rimadyl)
Meloxicam (Metacam)
Reduce, swelling, heat, pain, and fever
Corticosteroids
Block the activation of cells when a pattern recognition receptor is bound.
Act EARLY in the inflammatory cycle.
Can be immunosuppressive as ahvve a broad range of actions
