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