Pathology 5: acute inflammation and the complement system Flashcards
What are the 5 cardinal features of acute inflammation?
- Calor (Heat).
- Rubor (Redness).
- Tumor (Swelling).
- Dolor (Pain).
- Functio Laesa (Loss of Function).
Name 3 cell types which act as sentinel cells in tissues ready to react to invading microorganisms or to cell damage.
- Macrophages.
- Dendritic cells.
- Mast cells.
Describe the four changes that take place to facilitate the movement of cells of the immune system from the blood stream to the tissues, mentioning one important mediator for each
- Vasodilation (mediated by histamine): increases blood flow
- Margination (mediated by integrins): integrins are adhesins molecules which allow immune cells to adhere to the endothelium
- Emigration (mediated by histamine, bradykinins, and leukotrienes): increased vascular permeability which allows movement of fluid and cells from the vessel into tissues
- Chemotaxis (mediated by leukotrienes and cytokines): attracts cells to site where needed
What causes acute inflammation? why does it happen? which cell characterises acute inflammation?
- Necrosis (DAMPS) or infection (PAMPS/MAMPS)
- to allow inflammatory cells + plasma proteins to escape from blood vessels + to enter the interstitium to remove dead cells or microbes
- neutrophils
What is the main cytokine produced by sentinel cells when they are activated by DAMPs and PAMPs?
Interleukin 1 (IL-1).
List the 5 steps of acute inflammation (the 5 R’s)
Recognition (of the injurious agent).
Recruitment (of leucocytes).
Removal (of the agent).
Regulation (of the response).
Resolution.
What is the difference between a cytokine and a chemokine?
- Cytokines = proteins produced by many cell types that can mediate and regulate inflammatory reactions. Cyto means cell and kine refers to kinesis or movement
- Chemokines = chemotactic cytokines. These are produced as a chemical cloud which spreads out from the source of inflammation and can attract specific white blood cells.
List the 5 important mediators of acute inflammation.
Hageman factor (Factor XII).
The complement system.
Mast cells.
Arachidonic acid metabolites.
Toll-like receptors.
What is the Hageman Factor?
- a factor produced by the liver as an inactive protein
- It circulates in the blood stream until it is activated by exposure to collagen.
What is the link between the clotting system and the inflammatory system?
Hageman factor activates the coagulation cascade and also activates the kinin system.
What are the 3 main functions of bradykinin?
Vasodilation.
Increased vascular permeability.
Pain.
What is the Complement System?
A system of pro-inflammatory proteins produced by the liver which circulate as inactive precursors until they are activated by 1 of 3 pathways.
List 3 ways in which mast cells can be activated
Tissue trauma.
Complement components C3a and C5a.
Cross-linking of IgE bound to the mast cell surface by antigen.
Describe the consequences of mast cell activation
Mast cells contain pre-formed histamine granules which can be quickly released causing blood vessels to dilate and to leak. Mast cells also cause a delayed response by producing leukotrienes.
What enzyme is required to generate arachidonic acid from membrane phospholipids and what drug class can stop this reaction?
Phospholipase A2 and steroids
What enzymes are required to generate Prostaglandins from Arachidonic acid and name 2 drugs which can block these enzymes?
Cyclooxygenase 1+2 (COX 1+2) and Aspirin/Non-steroidal anti-inflammatory drugs
What is produced when 5-lipooxygnease acts on Arachidonic acid?
Leukotrienes
List 4 effects of prostaglandin production in the context of acute inflammation
Vasodilation.
Increased vascular permeability.
Pain (PGE2).
Fever (PGE2).
List 4 mediators which can cause redness and heat (rubor and calor).
Histamine.
Prostaglandins.
Bradykinin.
Nitric oxide.
What causes fever in the context of acute inflammation?
Pyrogens (eg. lipopolysaccharide) cause macrophages to release interleukin 1 (IL-1) and tumour necrosis factor (TNF) which increase COX activity in perivascular cells of the hypothalamus. This causes production of PGE2 which raises the temperature set point.
What causes the swelling seen in acute inflammation?
Histamine (from mast cells) causes endothelial cells to contract and endothelial cells can also be disrupted. This results in leakage of fluid from post-capillary venules into the interstitial space.
What is oedema?
An excess of fluid in the interstitial tissue or serous cavities. Can be an exudate (a fluid high in protein containing cell debris) or a transudate (a fluid low in protein).
What is pus?
- an inflammatory exudate rich in leucocytes (mostly neutrophils), the debris of dead cells and in many cases microbes
What causes pain in the context of acute inflammation?
Bradykinin and PGE2 sensitise sensory nerve endings.
Which inflammatory cell predominates in acute inflammation and which can be raised in a full blood count in the setting of acute inflammation, such as in the setting of an acute bacterial infection?
Neutrophil.
Which cell dominates 3 days after acute inflammation begins?
Macrophage.
How do macrophages kill organisms?
They ingest via phagocytosis helped by opsonins (C3b) and destroy phagocytosed material using enzymes (lysozyme) in secondary granules (Oxygen-independent killing).
List the 4 possible outcomes to acute inflammation.
Resolution and healing (mediated by IL-10 and TGF-beta).
Continued acute inflammation (mediated by IL-8 with persistent pus production).
Abscess formation.
Chronic inflammation (macrophages present antigen to activate CD4+ helper T-cells).
List two inflammatory cytokines that cause fever
- TNF alpha
- Interleukins (IL-1)
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