Inflammation (8) Flashcards
What is inflammation?
- non-specific response to cellular injury
- designed to remove the cause and consequence of injury
- complex and tightly regulated
What are the 4 main signs of acute inflammation?
- redness/rubor
- heat/calor
- swelling/tumor
- pain/dolor
(5. loss of function/functio laesa
What is vascularised tissue?
- epithelium
- interstitium containing immune cells (mast cells, macrophages)
- vascular endothelium w/ blood vessel running through, containing leukocytes, neutrophils, some macrophages
What are stages that follow damage?
- inflammatory signals (PAMPs, DAMPs) released in response to non-apoptotic cell death (necrosis) and detection of foreign material e.g. bacteria
- vasodilators released: mainly histamine, nitric oxide–> signal onto vascular endothelium
- vascular changes: increased permeability/breakdown of tight junctions, dilation, inc. blood flow, plasma leakage
What are the benefits of vascular permeability and leakage?
- inc. antibodies
- inc. protein
- inc. fluid barrier
- inc. leukocyte migration
What is exudate?
fluid barrier: fluid, proteins and cells that have seeped out of a blood vessel
How does CXCL8/IL-8 recruit neutrophils to the site of inflammation?
- IL-8 is a chemokine
- its receptors CXCR1 and CXCR2 are expressed on neutrophils and are G-coupled 7-transmembrane proteins
- so neutrophils are drawn towards site
What are the steps in neutrophil extravasation?
- chemo-attraction: cytokine or chemokine signal causes endothelial upregulation of adhesion molecules e.g. selectins and neutrophils to upregulate complementary adhesion molecules
- rolling adhesion: neutrophil engages endothelial lining and rolls along, binding to selectins
- tight adhesion: integrin activation from low to high affinity–> enhances binding to ligands
- transmigration: rearrangement of cytoskeleton and extension of pseudopodia, mediated by PECAM interactions on both cells–> neutrophils pass through membrane
What are the neutrophil functions at the site of inflammation?
- pathogen recognition e.g. use of TLR4 and CD14 to identify lipopolysaccharides on gram-ve bacteria
- pathogen clearance: phagocytosis, netosis (engulfing of bacteria in DNA nets)
- cytokine secretion–> recruitment and activation of other immune cells
How does phagocytosis work?
- large particles are engulfed into membrane-bound vesicles (phagosomes)
- phagosome fuses w/ lysosomes (vesicles w/ enzymes e.g. lysozyme that degrade bacterial membrane)
- forms phagolysosome
- exposed to reactive oxygen species and antimicrobial peptides e.g. defensins
How is acute inflammation resolved?
- activated neutrophils and inflammatory mediators have a short half life, so die quickly
- macrophages recruited, and clear dead cells
- repair and healing of membrane
What are some diseases characterised by chronic inflammation?
- rheumatoid arthritis
- asthma
- inflammatory bowel disease
- glomerulonephritis
- hepatitis
- psoriasis
- multiple sclerosis
What are some diseases associated with granulomatous inflammation?
- TB
- leprosy
- foreign body granuloma
- tumour reactions
- sarcoidosis
- Crohn’s disease
What are persistent inflammatory stimuli that lead to chronic inflammation?
- persistent/prolonged infection e.g. TB
- persistent toxic stimuli e.g. allergens, pollutants
- unclearable particulates e.g. silica
- autoimmunity e.g. self-antigens
What immune cells are found at sites of chronic inflammation?
- inflammatory macrophages
- T cells
- plasma cells (secrete antibodies)
