Inflammation Flashcards
7 types of inflammatory mediators
Histamines
Arachidonic acid metabolites
Cytokines
Chemokines
Reactive molecules
Platelet activating factor PAF
Plasma proteases
Histamines: function in inflammation, where found, released by what cells, binds with what receptor
○ First responder in acute reactions
○ Found in connective tissue near blood vessels
○ Released by mast cells when in contact with allergen or injury
○ Relaxes arterioles and increases vascular permeability
○ Smooth muscle in bronchioles constrict
○ Binds with H1 receptors on endothelium. H1 blocking medications mediate histamine responses in allergic reactions etc.
3 types of arachidonic acid metabolites
Leukotrines LT
Prostaglandins
Thromboxane
Leukotrines LT: function in inflammation, where found, what cells release it, what pathway does it use
§ Lipooxygenase pathway
§ Similar to histamines except they are not preformed but instead synthesized when needed, and show up on the scene a little bit later
§ Promote chemotaxis
§ Constricts pulmonary airways and increases vascular permeability
Increase cellular adhesion
Cyclooxygenase pathway
Used by inflammatory mediators, specifically arachidonic acid metabolites prostaglandin and thromboxane. Inhibited by aspirin and NSAIDs.
PAF platelet activating factor
Particularly seen in allergic responses and shock,
Causes platelets to aggregate, bronchoconstriction, vascular permeability, activate neutrophils and recruit eosinophils
Plasma proteases
Type of inflammation mediator, circulating pre-formed in plasma and made by the liver
3 types of plasma protease
Clotting system
Complement system
Kinin system
Clotting system
Activated during final stage of vascular phase of inflammation
Stop bleeding and further inflammatory response
Complement system
Many plasma proteases make up complement system, when activated they assist inflammation by increasing vascular permeability, vasodilation and facilitating phagocytosis.
Cascade/domino effect where they create more and more of themselves
Kinin system
One of the systems that causes pain in inflammatory response
Activation of kinin system results in release of bradykinin, which increases vascular permeability, contraction of smooth muscle, dilations of blood vessels, and pain.
Cytokines: role in inflammatory response, two major cytokines in inflammation, important cells for release, function
Agitators of inflammatory response, signaling molecules
TNF and IL (interleukin) two major cytokines in inflammation
Produced by many cells but particularly by macrophages
Increase adhesion to endothelium
Release free radicals and more cytokines
Cause systemic responses by affecting the hypothalamus, including fever, hypotension, increased HR, anorexia, release of neutrophils, and corticosteroids.
Chemokines
Bind to endothelium or CT
Recruit immune and inflammatory cells
Reactive molecules
Nitric oxide (NO): in granules of neutrophils smooth muscle relaxer, prevents platelet aggregation, recruits leukocytes
Reactive Oxygen Species (ROS): free radicals*: upregulate immune response by damaging tissue
Vit C and E antioxidants help downregulate
What WBCs are granulocytes
Neutrophils, eosinophils, basophils, mast cells
Neutrophils
primary phagocyte, arrives early at site of inflammation. Neutrophils are granulocytes and release enzymes and antibacterial material as well as reactive molecules hydrogen peroxide and nitric oxide that help destroy debris.
Monocytes
largest of circulating WBCs and act as macrophages. Monocytes and macrophages produce inflammatory mediators including prostaglandins, leukotrines, platelet activating factor (PAF), cytokines (IL and TNF).
Macrophages
produce a lot of IL and TNF cytokines
Eosinophils
circulate in the blood and are recruited to tissues. Increase during allergic reactions and parasitic infections. Granules contain protein that is toxic to parasitic worms and play an important role in allergic reactions.
Basophils
Circulating granulocytes structurally and functionally similar to mast cells. Granules contain histamine and other mediators.
Mast cells
do not circulate, are lodged in tissues. Granulocytes, release histamines and cytokines from their granules. Also synthesize lipid mediators-arachidonic acid metabolites such as leukotrines, thrombaxone, prostaglandins and PAF. Stimulate other inflammatory cells to synthesize cytokines and chemokines.
TNF and IL
two major cytokines of the inflammatory response. Released by macrophages primarily. Agitators of immune response, increase cell adhesion to endothelium, recruit free radicals and more cytokines. Cause systemic inflammatory responses when affecting hypothalamus.
Free radicals
Free radicals: released by neutrophils, unpaired electron causes high reactivity, non-specified damage to microbes, cells, and tissues
