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What are the cardinal signs of inflammation?
Heat, redness, swelling, pain, loss of function
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List some of the benefits of inflammation
- Dilution of pathogens, toxins
- Killing/sequestering/degrading pathogens, foreign material, necrotic tissue, neoplastic cells
- Providing wound healing factors
- Restricting movement allowing time for repair
- Increasing temperature to inhibit replication of pathogens
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List some of the disadvantages of inflammation
- Excessive or prolonged inflammatory responses can cause:
- Immune mediated diseases
- Hypersensitivity reactions
- Asthma
- Lymphplasmacytic stomatitis/fascitis
- Inflammatory bowel disease
- Idiopathic pulmonary fibrosis of West Highland White Terriers
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What are the two classes of inflammatory mediators?
Cell derived and plasma derived
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Give examples of cell-derived mediators
Platelets, neutrophils, monocytes/macrophages, mast cells, histamine
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Give an example of a plasma derived mediator
Complement proteins, kinins
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Where are plasma derived inflammatory mediators made?
In the liver
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What stimulates mediators of inflammation?
- Microbial products and necrotic material (PAMPs and DAMPs)
- Proteins of complement, kinin and coagulation systems
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Which cell derived mediators are vasoactive amines?
Histamine and serotonin
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What type of cell is histamine mostly found in?
Mast cells
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What happens when histamine and serotonin are released?
Dilation of arterioles and increased permeability of venules
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What stimulates serotonin release?
Platelet aggregation
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Which cell derived mediators are arachidonic acid metabolites?
Prostaglandins, leukotrienes (LTs), lipoxins
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What are arachidonic acid metabolites derived from?
Arachidonic acid in the cell membrane
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What pathway produces a) prostaglandins b) LTs and lipoxins?
- a) Cyclooxygenase pathway
- b) Lipoxygenase pathway
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What cell type secretes leukotrienes?
Leukocytes
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True or false: lipoxins facilitate inflammation?
False: they INHIBIT inflammation. Particularly inhibit leukocyte recruitment.
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What type of drugs inhibit a) the entire arachadonic acid pathway b) COX-1 and COX-2 pathways?
- a) Corticosteroids
- b) NSAIDs
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What type of cell mainly produces cytokines TNF and IL-1?
Activated macrophages
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What stimulates the secretion of TNF and IL-1?
Endotoxin, other microbial products, immune complexes, physical injury, etc
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What effects does TNF and IL-1 have after their release?
Effects on endothelium, leukocytes, fibroblasts, induction of systemic acute phase reactions and FEVER
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Give examples of other cell derived mediators
Chemokines, Platelet activating factor, Reactive oxygen species, Nitric oxide, Lysosomal constituents of leukocytes, neuropeptides
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In what form does complement circulate around the body?
In an inactive form in plasma
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Describe the steps involved in complement activation
- Proteolysis of C3
- Release of C3a and C5a (anaphylatoxins)
- Formation of membrane attack complex
- Result in phagocytosis
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What are the three main functions of the complement system?
- Inflammation
- Phagocytosis
- Cell lysis
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How does the complement system cause a) inflammation b) phagocytosis c) cell lysis?
- a) C3a and C5a are released which causes histamine release from mast cells. This increases vascular permeability and vasodilation.
- b) C3b act as opsonins and promotes phagocytosis
- c) deposition of MAC complex on cells causes lysis of cells
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What are the three pathways that activate the complement cascade?
Alternative pathway, classical pathway and lectin pathway
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Coagulation begins with factor ... activation?
XII
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How does inflammation promote clotting?
Via production of coagulation factors, makes endothelial surfaces prothrombogenic, inhibits anticoagulation mechanisms
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What molecule involved in the coagulation system promotes inflammation?
Thrombin
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What are kinins?
Vasoactive peptides
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What effects does bradykinin have after its release?
Increases vascular permeability, contraction of smooth muscle, dilation of blood vessels and pain
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Which kinin is a potent activator of factor XII?
Kallikrein
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What other kinin is activated by kallikrein?
Bradykinin
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