2C - The chemical Mediators of Inflammation and Immunity

Question 1

Three major types of chemical mediators

Answer 1

Preformed chemicals, synthesized, plasma proteins

Question 2

Preformed chemicals

Answer 2

such as histamine - stored in granules - rapid release and action

Question 3

Synthesized chemicals

Answer 3

cytokines and prostaglandin are formed after an inflammatory cell has injured or activated

Question 4

Plasma Proteins

Answer 4

that become activated once an inflammatory process has already started

Question 5

Checks and balances of the immune system

Answer 5

◦ Chemical mediators of inflammation all have
‣ Short half lives and decay rapidly
‣ Are destroyed enzymatically
‣ Are scavenged by protective mechanisms such as anti-oxidants
‣ Are blocked by endogenous inhibitors

Question 6

Why is histamine an example of preformed chemical mediator

Answer 6

the effects are almost immediate but do not last long
◦ Histamine is found in the granules of mast cells and basophils
‣ Increase vascular permeability, vasodilation (hyperemia), pain and itching
‣ Effects are almost immediate (w/in 1-2min) transient (lasts only 30 min)

Question 7

Cytokine

Answer 7

• Cells communicate via chemical messengers called cytokines, that are synthesized in response to tissue damage
◦ Cytokines regulate cells involved in the immune response
◦ Cytokines are produced by many cell types including lymphocytes, macrophages, and other inflammatory cells, endothelial cells and epithelial cells and connective tissues cells
• Cytokines modulate (enhance or suppress) the expression of other cell activities during inflammation

Question 8

Chemokine

Answer 8

A chemokine is a cytokine that attracts cells to the site of injury

Question 9

Chemotaxis

Answer 9

attraction of cells to the site of injury via chemokine

Question 10

Examples of cytokines and their functions

Answer 10

‣ IL-2 activates T-lymphocytes
‣ IL-3 activates bone marrow to produce more white blood cells
‣ IL-4 suppresses the immune response
‣ IL-17 receipts macrophages and neutrophils to the site of inflammation
‣ Interferons (IFNα) are released by cells in response to viruses and neoplasia to protect neighboring cells

Question 11

Complement Proteins

Answer 11

plasma proteins that are made in the liver and are normally inactive in the blood
◦ Activated by both innate and adaptive immune response

Question 12

Difference of Complement Proteins when they are activated by the different sides of the immune system

Answer 12

‣ Adaptive
• Complement is activated by Antibody-Antigen complexes (the Classic Pathway)
‣ Innate
• Complement is activated bacterial and fungal products
◦ The alternative pathway
◦ The mannose binding lectin pathway

Question 13

Activated complement proteins

Answer 13

◦ Opsonins
◦ Attract leukocytes (chemotaxis)
◦ Directly attack bacteria
◦ Stimulate histamine release from mast cells
‣ Many components of complement bind together to form the membrane attack complex

Question 14

MAC

Answer 14

membrane attack complex (MAC) - forms a hole in the cell membrane

Question 15

Arachidonic Acid

Answer 15

(AA) is a 20 carbon polyunsaturated fatty acid derived from linoleum acid present in a cell membranes

Question 16

Steps to create Arachidonic Acid Metabolites

Answer 16

◦ Cell damage and other chemical mediators of inflammation, like complement and IL-1 activate phospholipase
◦ Arachidonic acid metabolites are released from cell membranes by phospholipase
◦ Different AA metabolites are released from the cell membranes of different cells

Question 17

The two pathways to create AA metabolites

Answer 17

‣ COX (cyclo-oxygenase) → prostaglandins and thromboxjnes

‣ Lipoxygenase → leukotrienes and lipoxins

Question 18

Important AA products

Answer 18

◦ PGI1 (Prostacyclin) is released from endothelial cells (line BV) and reduces blood clotting
◦ TXA2 (Thromoboxane) is released from platelets-promotes clot formation
◦ PGF2α from endothelial cells causes vasoconstriction of smooth muscle
◦ PGE2 released from epithelial cells, fibroblasts and smooth muscle cells promotes fever
◦ The leukotrienes and lipoxins released from mast cells and macrophages - increase chemotaxis and promote vascular permeability and vasodilation

Question 19

Fever benefits and side-effects

Answer 19

• Fever is one of the benefits and one of the side effects of inflammation and the products of the AA pathway called PGE2
◦ Benefits : an increase in body temperature, causes vasodilation (increase blood flow to the area) and also inhibits the replication of some microbial agents
◦ Side-effects : makes you feel bad and if prolonged can be detrimental to health tissues
‣ Animals go off their food and decrease production

Question 20

Difference between fever and hyperthermia

Answer 20

• Fever is different form hyperthermia and results from resetting of the hypothalamic temperature center
◦ The effect of PGE2 affects the hypothalamus to reset the body’s thermostat, telling the body to heat up → animal shiver and seek warmth with blankets and hot showers to elevate the body temp
‣ They will feel warmer than normal to touch
◦ Hyperthermia → body wants to cool
◦ Fever → body wants to be warmer

Question 21

NSAIDS function

Answer 21

◦ Non steroidal anti-inflammatory drugs, NSAIDS, are used to treat the symptoms of fever in humans and animals
‣ NSAIDS block the cyclooxygenase (COX) pathways of the arachidonic acid metabolism
‣ Aspirin, ibuprofen and naproxen are COX 1 and COX 2 inhibitors
‣ Highly selective - newer generation NAIDS such as Meloxicam only COX-2 → less side effects

Question 22

COX 1 inhibitor

Answer 22

constitutively expressed and present in almost all tissues
‣ Housekeeping enzyme with roles in homeostasis, protects the renal medulla, and helps protect the gastric mucosa from acid by increasing mucous production

Question 23

COX 2 inhibitor

Answer 23

induced by exogenous and endogenous stimuli and is present in leukocytes, endothelial cells of blood vessels and synovial fibroblasts

Question 24

The role of corticosteroids

Answer 24

◦ Corticosteroids act right at the beginning of the pathway → many side effects

Question 25

The Role of omega three fatty acids

Answer 25

◦ It is though that omega 3 fatty acids may be protective-chemical mediators produced from this pathway are resolving and protecting

Question 26

transferrin lactoferrin

Answer 26

• Other important chemical mediators are iron binding proteins called transferrin lactoferrin
◦ Iron is an essential nutrient for bacterial replication
◦ These host proteins present in body secretions such as saliva and milk bind iron and make it unavailable to bacteria
◦ Some bacteria counteract this with Siderophores that chelate iron and remove it from the iron binding proteins

Question 27

Chemical mediators of the acute inflammatory response

Answer 27

◦ Kinins - tachykinin and Brady kinin are peptides that act on blood vessels
◦ Platelet activating factor
◦ Oxygen derived free radicals and nitric oxide
◦ Antimicrobial peptides - defensins
◦ Acute phase proteins - produced by the liver that increase in concentration during inflammation
‣ Eg C-reactive protein and fibrinogen
‣ Elevated fibrinogen concentration in the blood of cattle is one of the earliest indicators of acute inflammation