Lecture 4: inflammation and inflammatory mediators

Question 1

Acute inflammation is

Answer 1

A protective response
Innate immunity
Often, but NOT always, ,caused by infection
Trauma

Question 2

Classic signs of inflammation

Answer 2

Pain
Redness
Immobility
Swelling
Heat

Question 3

triggers of inflammation

Answer 3

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

Question 4

Mechanisms of inflammation

Answer 4

Sentinel cells produce a variety of mediators
Vasodilation
Increased capillary permeability
Increased sensitivity to pain
Initially the predominant inflammatory cell is the neutrophil

Question 5

Sentinel cells do what in inflammation

Answer 5

Sentinel cells produce a variety of mediators.
Promote blood flow
Attract cells, particularly PMNs
Improve phagocytosis

Question 6

Vasodilation is caused by what in inflammation

Answer 6

Histamine and prostaglandins are released by macrophages, mast cells and neutrophils.
Increased blood flow
Which signs?
Redness and heat

Question 7

Increased capillary permeability is caused by what in inflammation

Answer 7

Histamine and prostaglandins
Exudation of fluid
Which sign?
Swelling

Question 8

The neutrophil does what for inflammation

Answer 8

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

Question 9

Inflammation is further activated by

Answer 9

Binding pathogens or damaged tissue at their pattern recognition receptors
Products of activated complement

Question 10

Inflammation is stimulated to

Answer 10

Phagocytose
Kill ingested material.

Question 11

Activation of clotting

Answer 11

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

Question 12

Chronic inflammation is caused by

Answer 12

Neutrophils decrease
Macrophages and lymphocytes dominate in tissue.
Numbers in blood can increase.
Fibrous tissue is produced.

Question 13

Healing is initiated by

Answer 13

Insult is removed by phagocytosis and killing.
Inflammatory mediator production and inflammation stops!
Damaged tissue replaced by
New tissue
Fibrous tissue (scarring)

Question 14

The systemic response of inflammation in moderate and severe cases

Answer 14

In moderate and severe inflammation there is a whole-body response
Especially likely in bacterial/viral infections

Question 15

Blood neutrophils do what in inflammation

Answer 15

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.

Question 16

Fever is caused by and does what

Answer 16

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

Question 17

Systemic response to inflammation

Answer 17

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

Question 18

Liver does what

Answer 18

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.

Question 19

Part of the clotting system

Answer 19

Fibrinogen, prothrombin
This is why fibrinogen is measured on CBCs in large animals.

Question 20

Acute phase proteins are

Answer 20

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.

Question 21

Negative acute phase proteins are

Answer 21

Levels of these proteins decrease with inflammation.
The most important are:
Albumin provides source of aa
Transferrin transfers iron

Question 22

Common methods for controlling inflammation

Answer 22

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