Acute and Chronic Inflammation Part 1 Flashcards
What is inflammation?
Inflammation is a protective repose to tissue insult or injury tied at eliminating the cause of injury, remove damaged cells and initiate repairs
State the 5 cardinal signs of inflammation
- Calor (heat/ warmth)
- Rubor (redness/ erythema)
- Tumor (swelling)
- Dolar (Pain)
5/ Functio laesa (Loss of function )
Who are the major players in an inflammatory response?
- Circulating plasma proteins and cells of the immune system
- Vasculature and it’s endothelium
- Liver production of proton soft complement, clotting and cute phase
Name some of the CELLS involved n the inflammatory repose
- Mast cells
- Macrophages
- Monocytes
- Lymphocytes
5 Polymorphonuclear leukocyte - Plasma proteins
7 Extra cellular matrix proteins - Fibroblasts
What role do mast cells have in the inflammatory response?
They are source of mediators
What role do monocytes have in the inflammatory response?
They form macrophages
What role do macrophages have in the inflammatory response?
- They eliminate microbes, dead tissue
2. They are a source of mediators
What role do fibroblasts have in the inflammatory response?
They are a source of mediators
What role do plasma proteins have in the inflammatory response?
- Compliment: mediators of inflammation, elimination of microbes
- Clotting factors and kininogens: mediators of inflammation
What role do Polymorphonuclear leukocyte have in the inflammatory response?
They eliminate microbes and dead tissues
When is an inflammatory reaction triggered?
Inflammation is induced by chemical mediators that are produced by host cells in response to injurious stimuli such as an infectious agent or foreign bodies
Name the 5 steps of the inflammatory response
- RECOGNITION of the injurious stimulus
- RECRUITMENT of leukocytes
- REMOVAL of the agent causing the injury
- REGULATION of the response
- RESOLUTION of the response
What are the negatives of inflammation?
Cells involved in the inflammatory response can cause damage to healthy tissues
What will happen if an inflammation causing stimulus isn’t removed?
Injury wil persist which will result in a state of chronic inflammation
What can inflammation cause?
- Very strong inflammatory reaction
- Prolonged reaction
- Response is inappropriate
Describe the onset and duration of acute inflammation
It has a fast onset that generally lasts for a few mins- days
Describe the onset and duration of chronic inflammation
It has a slower onset and lasts for months-years
Which cells are involved in treating acute inflammation?
PMSs and macrophages
Which cells are involved in treating chronic inflammation?
Macrophages and lymphocytes
what effect does acute inflammation have on the body?
Results in rapid delivery of leukocytes and plasma proteins to injury sites
What do leukocytes do?
They clear infection and dead cells
Name the 2 major group of activities that occur to relieve acute inflammation
- Vascular changes
2. Cellular events
What vascular changes occur in repose to acute inflammation?
- Vasodilation
- Vascular permeability
- Endothelial cell activation
What cellular events occur in repose to acute inflammation?
- Leukocyte recruitment (mainly PMNs)
2. Activation of leukocytes infiltrating tissue.
How is an injurious stimuli RECOGNISED?
Phagocytes, Dendritic cells and epithelial cells express Pattern recognition receptors to recognise and bind to distinct molecular patterns not seen in healthy vertebrate cells
What do PRRs do?
Pattern recognition receptors recognise and bind to distinct molecular patterns not seen in healthy vertebrate cells.
Which cells are key to initiating inflammation?
Macrophages
Where are macrophages food?
Macrophages reside in almost all tissues
What do macrophages do?
They engulf and invade pathogens and debris which triggers the to release pro inflammatory cytokines and chemokine
Give examples of pro inflammatory cytokines
- TNF-alpha
- IL-1beta
- IL-6
Give examples of pro inflammatory Chemokine
- CXCL8 (IL-8)
What are cytokines secreted in response to and what do they do?
Cytokine secreted in response to a stimulus, affect the behaviour of cells
What are Chemokine and what do they do?
Chemokine a chemoattractant protein that stimulates the migration of cells
Where are mast cells found?
They are located close to body surfaces
What do mast cells release?
Release preformed histamine from granules.
What do mast cells do?
They have an anti parasitic activity and are a key player in allergic repossess
Where do pattern recognition receptors acquire their specificity?
Specificity is genome encoded (NO VDJ recombination)
Where are pattern recognition receptors expressed?
On all cells of a certain type
How are mast cells triggered?
Mast cells express an FC receptor that bind to IgE
Mast cell when triggered will collect and be coated with IgE
These IgE antibodies will then bind to their complimentary antigen not eh pathogen and this will trigger the mast cell to degranulate
Where are epithelial cells found?
They Line our mucosal surfaces eg gingival epithelial cells
What do epithelial cells express?
They express PRRs
What role do epithelial cells play in the inflammatory response?
They maintain homeostasis with commensal bacteria, but can respond to pathogens, initiating inflammatory responses by secreting CXCL-8, TNF-α , IL-1β, IL-18 and antimicrobial peptides.
What are toll like receptors located to do
They are Located to allow extracellular or endosomal recognition.
What structure can toll like receptors have?
Either Heterodimeric or Homodimeric structures
What does TLR-3 recognise?
Double stranded RNA
What does TLR-7 recognise?
Single stringed RNA
What does TLR-9 recognise?
Unmethylated CpG DNA
Where is single stranded RNA normally found?
- Cell nuclei
2. Cytoplasm
Where is single stranded RNA NOT found?
The endosomal space
The Heterodiamer of TLR-2 and TLR-6 will recognise what?
Diacyl lipoprotein
The Heterodiamer of TLR-2 and TLR-1 will recognise what?
Triacyl lipoproteins
What does TLR-5 recognise?
Flagellin
What does TLR-4 recognise?
LPS
Name receptors on cells that recognise foreign molecules
- Toll like receptors
- NOD like receptors
- RIG-I like receptors
- Lectin like receptor
What do lectin like receptors recognise?
Recognise polysaccharide molecules like those found on fungi
What is another name for NOD like receptors?
NLRs
Where are NOD like receptors found?
In the cytosolic space to provide cytoplasmic recognition
What do NLRs recognise?
Bacterial lipids
What do RIG-I do?
They bind to viral RNA that has an unmodified 5 prime triphosphate
Where are RIG-I found?
In the cytosolic space to provide cytoplasmic recognition
What is another name for The NLRP3?
NALP 3
What is The NLRP3 ?
It is a NOD like receptor that recognises dead cells
What does the NLRP3 receptor do?
It forms a complex in the cytoplasms of our cell called the NLRP3 inflamasome
What does the NLRP3 inflammasome do?
t cleaves and activates IL-1 beta
What does the NLRP3 inflammasome activate?
The zymogen form of caspase 1
What does the NLRP3 inflammasome do?
Recognises:
- Dead cell components
- Extracellular ATP uric acid
- Crystals
- Some pathogenic bacterial components
Following recognition of a foreign body what happens next in inflammation?
Leukocytes are RECRUITED
What vascular events occur when leukocytes are being recruited?
- Vasodilation
- Vascular permeability is increased
- Endothelial cells are activates
What is vasodilation and what does it do?
It is the widening of blood vessel calibre to increase blood flow
What does increased vascular permeability permit?
Permits the extravasation of plasma fluid and proteins to exit and enter the tissues
What changes occur when endothelial cells are activated?
The luminal vessel surfaces change and blood flow speed is reduced to allow leukocytes to pass through the endothelial layer (this allows them to gain access to the tissues)
Which cardinal sign of inflammation is caused by vasodilatation?
- Calor (heat/ warmth)
2. Rubor (redness/ erythema)
What induces endothelial cell contraction?
- Cytokines IL-1 and TNF (tumour necrosis factor)
2. Histamine and Kinins
Which cardinal sign of inflammation is caused by increasing vascular permeability?
Oedema
Describe the differences between a healthy blood vessel land an inflamed blood vessel?
Inflamed blood cell:
- is wider
- Has gaps between the endothelial cells
What does the gap between endothelial cells in inflamed vessels allow for?
Allows for fluid to leak out
What is the fluid that leaks out of vessels called?
Exudate
What is exudate formed of?
- White blood cells
- Red blood cells
- high levels of Protein
Name the most important exudate formed in the mouth
Gingival crevicular fluid
When does the flow and volume of GCF increase?
When you get gingival inflammation in gingivitis and periodontitis
What does a leaky endothelium allow?
Allows for inflammation to occur
How does a leaky endothelium contribute to inflammation?
- Extra proteins are delivered to inflamed site
2. Cells can exit more easily
What causes a leaky endothelium?
Endothelial cell contraction
Which cell activates the zymogen form of caspase 1?
The NLRP3 inflammasome
What induces endothelial cell contraction?
- Cytokines
- IL-2
- Tumour necrosis factor (TNF)
- Histamines and kinins
Give some cellular events that occur to aid leukocytes recruitment
- Margination
- Rolling
- Stable adhesion
- Transmigration
- Chemotaxis
What happens to blood flow when blood vessels dilate?
Blood Flow is reduced
What is margination?
The fact that red blood cells move quicker through the lumen of the vessel causing white blood cells to gather on the sides
What exaggerates margination?
Vessel dilation and reduced blood flow as more white blood cells are found at the edge of the blood vessels
What are the benefits of margination?
More WBC at the edges of eh vessel so they can diffuse out of the vessel more easily
Go through the process of rolling
- Pro inflammatory cytokines/ histamines activate endothelial cells
- Endothelial cells once activated will express adhesion molecules (Selectins) on the luminal surface
- Selectin molecules bind to Sialyl-Lewis X
- This binding is weak so keeps breaking and reforming causing the WBC to roll through the vessel
Give examples of adhesion molecules
- PECAM
- ICAM
- Selectins
What to selectin bind to ?
Sialyl-Lewis X
What is Sialyl-Lewis X ?
A modified glycoprotein
What is stable adhesion?
It is the interaction between integrins (leukocytes) and cell adhesion molecules (endothelium).
What happens as a result of stable adhesion?
The Interaction between the integrins and the endothelium is enough to stop the WBC from rolling
What is transmigration?
When the leukocyte squeezes through the intercellular endothelial junctions
Which molecule aids transmigration?
PECAM 1
What is transmigration sometimes called?
Diapedesis
After transmigration occurs what happens to the white blood cells
They undergo chemo taxis
what is chemotaxis?
Movement along a chemical gradient
Name some of the most predominant molecules present in the different stages of inflammatory infiltration
- Exudate (EG GCF)
- Neutrophil
- Monocytes/macrophages
