Lecture 6 Flashcards
What are the four signs of inflammation?
Redness, heat, swelling, pain
What is inflammatory exudate?
protein rich fluid leaked out of blood vessels in response to inflammation
What are the 8 effects of inflammation?
Delivery of nutrients and Oxygen to infection site
Generation of exudate to transport toxins allowing for an immune response
Generation of exudate to move antibodies and other substances into infection in order to neutralize pathogens
Mobilizes work force to remove dead cells damaged proteins etc
Mobilizes defense force to remove pathogens
Limits the spread of harmful agents
Provides digestive enzymes to remove the exudate when needed
initiates repair
What are the three ‘go’ signals for inflammation?
Neuronic release of bioactive peptides
Intracellular molecules are released from broken cells
Microbial products or toxins are recognised
What are DAMPs
Danger associated molecular patterns, molecules released when cells undergo lysis
What senses DAMPs?
Pattern recognition receptors
What are PAMPs?
Pathogen associated molecular patterns, which signal the presence of an infection
What senses PAMPs?
Pattern recognition receptors such as soluble complement proteins or cell bound toll-like receptors
What are the first two immune cells to respond to inflammation?
Basophils and macrophages
What is the purpose of basophils in inflammation?
To initiate an inflammatory response through mediator molecules
What are the mediator molecules released by maast cells?
Histamine, tryptases or proteases, lipid derived signals and cytokines
What is the purpose of vasodilatation in inflammation?
increased blood flow causes redness and heat
What is the cause of the increase in vascular permeability seen in inflammation?
The endothelial cells retract leaving gaps between them in response to inflammatory signals
What is the purpose of the increase in vascular permeability seen in inflammation?
To allow proteins to pass through the capillary resulting in the formation of exudate
What do more severe injuries result in with respect to vascular permeability?
The endothelial cells detach from the basement membrane resulting in persistent increases in vascular permeability
Why does inflammation lead to swelling?
The increased vascular permeability results in a blood pressure drop so less pressure forces the fluid into the vein resulting in a accumulation of fluid causing swelling and pain
What are the chemical mediators linked to swelling and pain in inflammation?
Prostoglandin E2 and Bradykinin
What are the four effects of both Vasoactive amines and tryptases?
vasopermeability, adhesion for neutrophils, synthesis of lipid mediators leading to vasodilatation, bronchoconstriction
What is the difference between Tryptases and Vasoactive amines?
While amines are stored in the granules of maast cells, tryptases cleaves protease activated receptors on maast cells, endothelial cells and neutrophils to cause the same physiological effects
What induces the formation of lipid mediator derivatives?
Inflammatory signals use Ca2+ to activate phospholipase A2 which cleaves membrane phospholipids to from the mediators
What is Platelet activating factor derived from?
Lysophosphatidylcholine, through the action of phospholipase A2
What are the affects of Platelet activating factor?
The same affects as tryptase/vasoactive amines as well as platelet aggregation
What does arachidonic acid do in the inflammation response?
Generation of acute phase proteins such as prostoglandins and leukotrienes
How are prostoglandins formed?
Arachidonic acid reacts with Cyclooxygenases
How are Leukotrienes formed?
Arachidonic acid reacts with 5-Lipoxygenase
What is the function of TXA2?
Vasoconstriction and platelet aggregation
What is the function of PCI2?
Vasodilation and platelet dissociation
What is the function of PGE2?
Vasodilation, pain, fever
What is the function of LTB4?
Neutrophil chemotaxis and activation
What are the functions of cysTC4,D4,E4?
Vasopermeability and bronchoconstriction
What are the four cascades of inflammation?
Coagulation, fibrinolytic, kinin, complement
What activates the coagulation cascade?
Tissue factor released from apoptotic endothelial cells and exposed basement membrane
What activates the fibrinolytic cascade?
Hageman factor FXII
What activates the complement cascade?
A series of convertases
What is the affect of the coagulation cascade?
Activation of thrombin resulting in fibrinogen conversion to fibrin causing clots
Protein activated receptors induce vascular permeability and platelet activating factor release causing its affects
What is the affect of the fibrinolytic cascade?
Generation of the protease plasmin degrades fibrin breaking down clots
Cleavage of Extracellular matrix and activation of matrix metalloproteases causing remodeling of the tissue
Activation of the kallikrein protein which activates the kinin system
What is the affect of the kinin cascade?
Kallikrein release the bradykinin protein resulting in vascular dilatation, vascular permeability and pain inducing affects
What are the cleavage products in the complement cascade system?
C3a, C3B, C5a and components of the membrane attack complex
What is the function of C3a and C5a?
Promote maast cell degranulation, vascular permeablilty and neutrophil chemotaxis
What is the function of C3B?
Oponisation
What is the function of C5b?
Part of the membrane attack complex for bacterial cell lysis
