Inflammation Flashcards
What is inflammation a response to?
Cellular injury
What are the four main signs of acute inflammation?
Redness
Swelling
Pain
Heat
What are the causes of inflammation?
Pathogens
Allergens
Auto-antigens
Physical damage
Extreme temperatures
Non-apoptosis cell death
What happens in acute inflammation?
Change in local blood flow
Structural changes in the microvasculature
Recruitment/accumulation of immune cells and proteins
What happens in the first stage of acute inflammation?
Steady state
What happens in the second stage (damage) of acute inflammation?
- Inflammatory signals
- Vasodilators released
- Vascular chnage
What are the inflammatory signals in acute inflammation?
Non-apoptotic cell death
Detection of foreign material
What vasodilators are released in acute inflammation?
Histamine
Nitric oxide
Wha are the vascular changes in acute inflammation?
Increased permeability
Dilation
Reduced flow
Plasma leakage
What benefits does increased vascular permeability and leakage bring?
Rapid movement of antibodies into site of inflammation specific to intruding pathogen
Recruiting proteins into tissue site —> increased activation of immune cells and source of protein for tissue repair
Recruitment of leukocytes
Formation of a physical barrier
What is exudate?
Fluid, proteins and cells that have seeped out of a blood vessel
What is the purpose of exudate?
Form separation between healthy and inflamed tissue
—> prevent inflammatory stimuli and pathogens from migrating into healthy tissue and causing further damage
What happens in the third stage (immune cell recruitment) of acute inflammation?
Recruitment of inflammation signals at site of damage
These chemokines diffuse out to form a gradient
Leukocytes expressing complimentary chemokine receptors migrate towards the chemokine source
What is an example of immune cell recruitment?
Chemokine: CXCL8 —> IL-8
Receptors: CXCR1 and CXCR2, g coupled 7-transmembrane proteins
Cell type: neutrophils
How does neutrophil extravasation work?
- Chemo-attraction
- Rolling adhesion
- Tight adhesion
- Transmigration
What happens in chemo-attraction in neutrophil extravasation?
Cytokines act on endothelial layer to promote upregulation of adhesion molecules
What happens in rolling adhesion in neutrophil extravasation?
Carbohydrate ligands in a low affinity state on neutrophils bind selectins and migrate along blood vessel
What happens in tight adhesion in neutrophil extravasation?
Chemokines promote low to high affinity switch in integrins —> enhance binding ti ligands
What happens in transmigration in neutrophil extravasation?
Cytoskeletal rearrangement and extension of pseudopodia to move cell into interstitium
—> mediated by PECAM interactions on both cells
What is neutrophil function at the site of inflammation?
- Pathogen recognition
- Pathogen clearance
—> phagocytosis
—> netosis —> take DNA out —> trap bacteria in ‘net’ —> allow macrophage to be recruited - Cytokine secretion
—> recruitment and activation of other immune cells
What happens in resolution of acute inflammation?
- Pathogen recognition
—> immune cells and antimicrobials will recognise infections/particulates - Short half life
- Macrophages
—> clear apoptosis cells
—> produce inflammatory mediators - Repair/wounding healing
What is persistent inflammatory stimuli?
Persistent/prolonged infection
Persistent toxic stimuli —> e.g allergens, pollutants
Unclearable particulates
Autoimmunity
What does distinct immune cell infiltrate include?
Inflammatory macrophages
T cells
Plasma
What are the good effects of macrophages?
Phagocytic
Cytotoxic
Anti-inflammatory
Wound repair
What are the bad effects of macrophages?
Cytotoxic
Inflammatory
Pro-fibrotic
What do T cells do in chronic inflammation?
Pro-inflammatory
Cytotoxic
Regulatory
What do B cells do in chronic inflammation?
Generate plasma cells —> secrete antibody
Protective, clearing infection
Inflammatory —> driving reaction against self
Can be local to inflammatory site or operate remotely
What is granulomatous inflammation?
Chronic inflammation with distinct pattern of granular formation
Triggered by strong T cell responses
Form against resistant agents
What is a granuloma?
Aggregation of activated macrophages —> barrier designed for clearance
What are the positive outcomes of acute and chronic inflammation?
Clear inflammatory agent
Remove damages cells
Restore normal tissue function
What are the negative outcomes of acute and chronic inflammation?
Excess tissue damage
Scarring
Loss of organ function —> organ failure
