Inflammation Lecture 1 Flashcards
Define what inflammation is
The response stimuli that can cause your body damage to protect it from danger/damage to promote healing
Stimuli can be pathogens, foreign proteins, response to noxious molecules and physical trauma
What are the 5 cardinal signs of inflammation
Heat- calor
Redness- rubor
Swelling- tumor
Pain- dolor
Loss of function
What are the three ways to describe the time scale of the inflammatory response
Onset
Resolution
Post-resolution
What is involved in the onset of the inflammatory response
Production of inflammatory mediators by resident cells
Infiltration of leukocytes
Elimination of pathogen and/or debris
What is involved in the resolution of the inflammatory response
Removal of inflammatory stimuli
Catabolism of pro-inflammatory mediators
Polymorphonuclear (PMN) death and efferocytosis
Influx of monocyte derived macrophages
What is involved in the post resolution of the inflammatory process
Influx of adaptive immune cells
Re-assembly of the tissue resident macrophages and dendritic cells
Adaptive immunity established
Body begins to adapt to pathogen and acts as an innate component
Describe the summary of inflammatory events when someone is cut by a splinter that contains pathogens
- Cell resonate under the skin that sense any damage through patient recognition receptors
- Mast and macrophage cells release signalling molecules that signal capillary bed
- Capillary bed receives neutrophils that will help get rid of pathogens on splinter
- Removal occurs via phagocytosis and resolution occurs to remove debris
Give an example of a sentinel cell and what it is
Bodies first line defence
Example: Mast cells, Macrophages
What is the role of mast cells and how are they activated
Role: Release pro inflammatory mediators like histamine, prostaglandins, and platelet activating factor
Activated by:
IgE, C3a, C5a
Fibrolytic cascade in blood
What is the role of endothelial cells
Role: respond to pro-inflammatory mediators to release mediators that cause vasodilation
Examples: Prostaglandins and NO (promotes heating)
How is the redness, swelling and heating triggered in inflammation
Cytokine and mediators
Vasodilation- increase blood flow to area
Vascular permeability- fluid in to injury area
What is the proteolytic cascade and give an example of it
Conversion of factor XIIa from plasma into pro-inflammatory products that activate complement cascade (C1 to C9)
Example:
C3a and C5a stimulate MAST cells and release histamine and other factors
What are the role of leukocytes
They are attracted to pathogens via chemotaxis to engulf, kill and digest micro-organisms
What are the roles of monocytes/macrophages
They eat up micro-organisms and cell debris
Release many factors to co-ordinate inflammatory response
examples: cytokines and chemokine
What does the resolution phase involve in inflammation
Healing and return of tissue back to normal function
Give three hormones that increase in non resolving inflammation
Increase TNF- persistence of inflammatory trigger
Increase IFNs- ongoing presence of inflammatory macrophages
Increase IL-6- failure to establish adaptive immunity
What is a cytokine or chemokine role
Protein/peptide signalling molecule that modulate function of other cells in inflammation and immunity
What are the major pro inflammatory cytokines that initiate most of the vascular and cellular events
TNF-alpha
Interleukin-1 (IL-1)
Explain each of the flush, wheal and flare reactions
Flush: arterial vasodilation
Wheal: oedema and swelling
Flare: sensory nerve induced dilatation- CGRP
What stimulates mast cell degeneration
C3a, C5a and IgE (recognises many allergens)
What are some the effects histamine has when it stimulates H1 receptors
Constriction of GI and bronchial smooth muscle
Dilation GI and bronchial smooth muscle
Dilates blood vessels via stimulation of endothelial cells
Itch normally associated with wound healign
What is the Eicosanoid structure and give examples of the types formed
Found on the lipid bilayer that is made up of polar phospholipid head and arachidonic acid
Examples: PGI, PGE, PGD, PGF, Thromboxane
Also known as PROSTAGLANDINS
What is the role of PGI2, PGE2 and PGD2
PGI2, PGE2 and PGD2 are all vasodilators
PGE2 plays role in thermoregulation of hypothalamus
What are Leukotrienes and its role
Made via arachidonic acid via lipoxygenases
Role:
constrict bronchial smooth muscle
Increase vascular permeability
Evoke wheal and flare reaction (similar to histamine)
What are antagonists of leukotrienes (drugs) and what are they used for
Used in asthma
Zafirlukast and MONTELUKAST
What are Lipoxins and its role
Formed by lipoxygenases (anti-inflammatory) properties
What does PAF (platelet activating factor) do
Stimulates signs and symptoms of inflammation (flush, wheal and flare) Induces hyperalgesia (pain)