Nonspecific Defenses of the Host
12. List the four cardinal signs of inflammation.
13. List the functions of inflammation.
14. Describe the effects of vasodilatation.
15. Describe the effects of increased permeability.
16. List the chemical mediators of inflammation.
17. Describe phagocyte migration.
19. Describe tissue repair.
20. Define fever.
21. Give the principal indicator of fever.
22. Define crisis.
23. Describe the induction of fever.
Inflammation is a bodily response to cell damage.
The four cardinal signs of inflammation, as described by the Roman physician and science writer Celsus, are:
The fifth sign, which is somethimes present, is loss of function, or functio laesa - this was originally described and added to the four signs described by Celsus by another Roman physician and science writer, Galen, but was popularized in the 1800s by Rudolph Virchow, the "Father of Modern Pathology".
Toll-like receptors (TLRs) and phagocytosis receptors are a subset of molecules known as pattern recognition receptors (PRRs). PRRs recognize "conserved molecular sequences" associated with a number of different pathogens, or PAMPs - pathogen associated molecular patterns. PRRs are found on the surface and in the cytoplasm of macrophages, dendritic cells, mucosal epithelial cells, endothelial cells, and lymphocytes.
Some secreted molecules recognize PAMPs and act as PRRs as well. For a moderate list of the PRRs click here.
When pathogens bind to TLRs cells are stimulated to release cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and chemokines, which act as chemoattractants for white blood cells and promote inflammation at the site of interaction.
Mast cells, injured tissue cells, neutrophils, lymphocytes, and basophils all release inflammatory mediators as well.
The release of histamine, kinins, and prostaglandins causes vasodilation and increased permeability of blood vessels.
Histamine causes vasodilation, increases vascular permeability, and is chemotactic for eosinophils.
Kinins cause clotting, vasodilation, increased vascular permeability, and pain.
- Factor XII (Hageman Factor) is activated by endotoxin, uric acid, calcium pyrophosphate, and basement membrane proteins (collagen).
- XIIa activates Factor XI to initiate clotting and cleaves prekallikrein to kallikrein.
- Kallikrein converts plasminogen to plasmin, HMW kininogen to bradykinin, and cleaves C5 to release C5a and C5b.
- C5a stimulates inflammation
Arachidonic acid metabolites
- PGE2 increases vascular permeability, sensitizes to pain, and is pyrogenic.
- PGI’s cause vasodilation.
- Thromboxanes cause vasoconstriction.
- Leukotrienes are produced by mast cells, basophils, macrophages, and eosinophils.
- LTB4 (SRS-A) is chemotactic, causes vasoconstriction, and increases endothelial stickiness.
- LTC and LTD cause bronchoconstriction, allergy, increase vascular permeability
Blood clots can form around an abscess to prevent dissemination of the infection.
Epithelial mucosal cells increase their release of b- defensins (broad spectrum antimicrobial proteins) when the epithelial barrier has been breached and the underlying connective tissue is inflammed.
Phagocytes have the ability to stick to the lining of the blood vessels (margination).
They also have the ability to squeeze through blood vessels (emigration).
PMNs show up first and release ROI (reactive oxygen intermediates), like superoxide anions, hydroxyl ions, hydrogen peroxide, and the enzyme myeloperoxidase, which converts hydrogen peroxide to hypochlorous acid (HOCl, which dissociates to H+ and OCl-, the hypocholorite anion, basically bleach). PMNs also release defensins and are phagocytic.
Pus is the accumulation of damaged tissue and dead microbes, granulocytes, and some macrophages. Generally macrophages show up late to clean up the cellular debris (debride the wound) and set the stage for wound healing.
A tissue is repaired when the stroma (supporting tissue) or parenchyma (functioning tissue) produces new cells.
Stromal repair by fibroblasts produces scar tissue.
Fever is an abnormally high body temperature produced in response to a bacterial or viral infection.
Bacterial endotoxins and interleukin-1 can induce fever.
A chill indicates a rising body temperature; crisis (sweating) indicates that the body’s temperature is falling.