3. Chemical Mediators of Inflammation. Flashcards
What are the 2 groups that chemical mediators are divided into?
Those that are derived from cells and those that are derived from plasma.
What are cellular chemical mediators?
Pre-made substances that are located in the cytoplasm of a cell.
When are cellular chemical mediators released?
Following the stimulation or lysis of that cell.
What are 4 examples of cellular chemical mediators?
Lipid Mediators.
Vasoactive amines.
Cytokines and chemokines.
Lysosomal contents from phagocytic cells.
What are plasma chemcial mediators?
Soluble factors that are found in the blood stream.
How are plasma chemcial mediators interconnected?
Via a cascade system, this means that when one subunit gets activated it then activates another and so on.
Lipid mediators are involved in what pathway?
The arachidonic acid pathway.
What enzyme is upregulated when there is damage to the PPL bilayer on cell membranes?
Phospholipase A2.
What is the function of phospholipase A2?
It breaks down the phospholipid bilayer and this forms arachidonic acid.
What happens to the arachidonic acid that is formed by the destruction of the cell membrane by phospholipase A2?
It is broken down by the cyclooxegenase pathway or the lipooxegenase pathway.
What enzymes break down arachidonic acid in the cyclooxegenase pathway ?
Cyclooxegenase-1 (COX-1).
Cyclooxegenase-2 (COX-2).
What is made by COX-1?
Thromboxanes and prostaglandins
What is made by COX-2?
Prostaglandins.
What is made by the lipooxegenase pathway?
Leukotrienes.
What is the role of COX-1 in healthy animals?
It helps with the protection of mucosal cells and renal function.
When are levels of COX-1 increased?
During inflammation.
When is COX-2 expressed?
During inflammation.
What is the role of the thrombaxanes that are upregulated during inflammation?
They produce vasoconstriction and platelet aggregation.
What are the 5 things produced by prostaglandins during inflammation?
Fever.
Pain.
Vasodilation.
Increased vascular permeability.
Leukocyte adhesion and chemotaxis.
How do NSAIDs affect inflammation?
They reduce the up regulation of COX-1 and COX-2.
This reduces the amount of thromboxane and prostaglandins.
This results in less redness, swelling, heat and pain.
What changes do we often see if we put an animal of NSAIDs for a long time and why do these changes occur?
Reduced renal function and reduced protection in mucosal areas.
As COX-1 enzymes are active in healthy animals and they are suppressed by NSAIDs.
Leukotrienes are involved in what kind of reactions?
Hypersensitivity and allergic reactions.
What are the 4 things that leukotrienes can cause in the body?
Smooth muscle contraction.
Vasodilation.
Leukocyte adhesion and chemotaxis.
Mucous secretion.
Do leukotrienes or histamine have a more potent response?
Leukotrienes are more potent but have a less rapid response.
What produces platelet activating factor following damage to the cell membrane?
Phospholipase A2.
Platelet activating factor is a lipid mediator.
What is the most potent activator of vascular permeability?
Platelet activating factor.
This means it increases the size of gap junctions in the vascular endothelium.
What are the 2 things that occur once platelet activating factor has been activated?
WBC chemotaxis and activation.
Platelet activation.
What are leukocytes?
White blood cells.
What is suppressed when an animal is given corticosteroids?
Phospholipase A2.
This causes widespread reduction of inflammation.
Do NSAIDs or corticosteroids have a better reduction of inflammation?
Corticosteroids, but they have more side effects.
What are 5 side effects of glucocorticoids?
Decreased mucosal protection.
Increased thirst and urination.
Increased blood sugar.
Panting and restlessness
Immunosuppression.
What are 3 examples of vasoactive amines?
Histamine.
Serotonin.
Nitric Oxide.
What are the 3 main cells that produce histamine?
Mast cells.
Basophils.
Platelets.
What cells produce serotonin?
Platelets.
What 2 cell types produce nitric oxide?
Macrophages.
Endothelial cells.
Do vasoactive amines act locally or systemically?
Both.
What is the result of the release of vasoactive amines?
Immediate vasodilation that lasts for a short time.
Interleukins are a class of what?
Cytokine.
What 4 things will interleukins and interferons respond to?
Infection.
Hypersensitivities.
Inflammation.
Cancer.
What cells produce interleukins and interferons?
Many different cells.
What is influenced by interleukins and interferons?
The innate and adaptive immune systems.
What 4 things can activate IL-1?
Fever.
Neutrophilia.
Activation of endothelial cells.
Activation of phospholipase A2.
What is stimulated by IL-1?
Acute phase proteins.
What 3 things activate TNF-alpha?
Shock.
Activation of neutrophils.
Activation of endothelial cells.
What is stimulated by the activation of TNF-alpha?
The production of other cytokines.
What interferon causes a shift from acute to chronic inflammation?
Interferon gamma.
What 2 things are activated by interferon gamma?
Macrophages.
Lymphocytes.
What is the role of IL-10?
Immune system suppression.
What are chemokines?
A subclass of cytokines that are involved in the activation of cells and in chemotaxis.
What chemokine activates neutrophils?
IL-8.
What chemokine activates eosinophils?
Eotaxin (CCL11).
What 4 chemokines activate lymphocytes?
CCL1.
CCL2.
CCL17.
CCL20.
What chemokine activates monocytes?
Monocyte chemoattractant protein 1 (MCP -1, CCL2).
Lysosomal components are found in what 2 immune cells?
Neutrophils.
Macrophages.
What are 3 examples of lysosomal components found in immune cells?
Reactive oxygen metabolites (free radicals).
Antimicrobial peptides
Enzymes.
The reactive oxygen metabolites found in lysosomal components of immune cells are reactive to what inflammatory mediators?
Pathogens.
Host cells.
Does thrombaoxane result in vasocontriction or vasodialtion?
Vasoconstriction.
What is the complement system comprised of?
Activated proteins that attack pathogens and enhance inflammatory responses.
What is the difference between binding in the classical pathway, the mannan-binding lectin pathway and the alternative pathway?
In the classical pathway antibodies bind to antigens.
In the mannan-binding lectin pathway lectins bind to mannose.
In the alternative pathway there is non-specific binding to the pathogen surface.
What is mannose?
A common sugar found on the surfaces of pathogens
What is activated when any one of the classical pathway, the mannan-binding lectin pathway or the alternative pathway are activated?
All the pathways end up forming C3-convertase which then forms the membrane attack complex.
What is the function of the MAC?
It bores holes in pathogens causing fluids to leak out.
What are the 2 anaphylatoxins on the MAC?
C3a.
C5a.
What is the role of the anaphylatoxins C3a and C5a?
Mast cell degranulation.
Vascular dilation, increased permeability.
Leukocyte adhesion and chemotaxis.
What is the opsonin on the MAC?
C3-B.
What occurs when C3-B is activated?
Enhanced phagocytosis by neutrophils and macrophages.
Why would an animal with a C3 deficiency be more at risk of developing bacterial meningitis?
As there is a much lower production of the subunits that form the MAC.
This means the immune response is not as effective.
What would happen if an animals had a defect in C1?
The classical pathway would not work and antibodies would not bind to antigens.
How will a C3 deficiency affect the immune response?
Decreased vascular response.
Reduced cellular response.
Reduced MAC response.
How will a C3 deficiency affect the immune response?
The classical pathway will not work.
When does the intrinsic pathway for clotting occur?
When there is a platelet plug in the subendothelium.
It always occurs when there is damaged tissue.
How does a platelet plug activate the the intrinsic pathway for clotting?
It activates factor 12 which starts the cascade.
What factor leads to the activation of the intrinsic clotting pathway?
Factor 7.
What factor is activated by both the intrinsic and extrinsic pathways?
Factor 10 which leads to the formation of fibrin.
What 2 things activate the enzyme kalliekrin?
Microbes.
Factor 12.
What happens once kalliekrin is activated?
It activates kininogens which then form various kinins.
When is the fibrinolytic system activated?
At the same time as the clotting cascade.
Why is the fibrinolytic system activated at the same time as the clotting cascade?
To prevent thrombosis from occurring.
Plasmin can activate what part of the clotting system?
C3.
A massive intravascular immune response promotes what 2 things?
Coagulation.
Fibrinolysis.
