inflammation Flashcards
- What is inflammation?
- What initiates inflammation?
Protective biological process that helps to remove damaged cells and clear toxins and infections
Non-specific response to cellular injury
Initiated when cellular damage (non-apoptotic cell death) leads to the release of damage associated molecular patterns (DAMPs) or the body detects pathogen associated molecular patterns (PAMPs)
causes cells in tissue to release a range of signals designed to induce inflammation
- What can chronic inflammation lead to?
- What is acute inflammation characterised by?
- How does Chronic inflammation occur?
Scarring and loss of tissue function due to repetitive rounds of inflammation
Rapid onset, and recruitment of innate immune cells, particularly neutrophils.
When acute inflammation cannot get rid of the inflammatory signal
adaptive immune cells recruited
- What are the 4 main signs of acute inflammation?
Redness (rubor)
Heat (calor) Swelling (tumour) Pain (dolor)
- List causes of inflammation
Pathogens
Allergens Auto-antigens Physical damage Extreme temperatures Non-apoptotic cell death
- What does the body release when there is damage done (e.g. wound in skin) ?
- What is the purpose of these chemicals?
Vasodilators (Histamine and nitric oxide)
Vascular changes:
Increased permeability
Dilation
Reduced flow
Plasma leakage into inflamed site
- What benefits do increased leakage and vascular permeability have?
Increases antibodies to site
increased proteins (inc activation of immune cells and provides proteins for tissue repair)
physical barrier
increased leukocyte migration
- What are the principle sources of Histamines and what are its actions?
- What are the principle sources of Prostaglandins and what are its actions?
Mast cells, basophils and platelets
Vasodilation, increased vascular permeability, endothelial activation
Mast cells & leukocytes Vasodilation, pain, fever
- What are the principle sources of Cytokines and what are its actions?
- What are the principle sources of Chemokines and what are its actions?
Macrophages, endothelial cells, mast cells
Endothelial activation, fever, malaise, pain, anorexia, shock
Leukocytes & activated macrophages Chemotaxis & leukocyte activation
- What are the principle sources of Complement and what are its actions?
- What is Exudate and what is it’s purpose?
Plasma (in liver)
Leukocyte chemotaxis & activation, opsonisation
Fluid containing proteins and cells that have seeped out of a blood vessel during inflammation acts as barrier and prevents leakage of inflammatory stimuli and harmful pathogens to surrounding tissue
- Outline the process of immune cell recruitment?
At the site of damage, inflammation and recruitment signals (e.g. chemokines) are produced, which diffuse out to form a gradient.
Leukocytes that have complementary chemokine receptors move to the chemokine source
- What is CXCL8 also known as?
- What receptors bind to the chemokine CXCL8?
- Which cell type most prominently expresses these receptors that bind to CXCL8?
Interleukin-8 (IL-8)
CXCR1, CXCR2, These are g-coupled transmembrane proteins Neutrophils This is why they are often the first cell type to be recruited to the site of inflammation
- List and explain the 4 steps of neutrophil extravastion?
- Chemo-attraction - production of cytokines and chemokines at the site of inflammation → endothelial up-regulation of adhesion molecules
- Rolling adhesion - Neutrophils have carbohydrate ligands in a low affinity state which bind to selectins (E.g. PSG1 - selectin P ligand)
- Tight adhesion - chemokines promote low→ high affinity switch integrins - enhances binding of neutrophil to endothelial wall
- Transmigration through endothelial wall → cytoskeletal rearrangement and extension of pseudopodia
- What is the last step of neutrophil extravasation mediated by?
- What 3 main things do neutrophils do at the site of inflammation?
PECAM interactions on both endothelial side and neutrophil side
1. Pathogen recognition e.g. - use of TLR4 & CD14 to identify lipopolysaccharides present in gram-negative bacteria 2. Pathogen clearance - phagocytosis and netosis 3. Cytokine secretion - Recruitment and activation of other immune cells
what is the process of phagocytosis?
what else do phagocytes have that help with killing cells?
large particles are engulfed into a vesicle (phagosome)
phagosome fuses with a lysosome (vesicle containing elastase and lysozymes)
forms a phagolysosome
reactive oxygen species- phagocyte NADPH oxidase
antimicrobial peptides - eg defensin
- What is the function of macrophages in the resolution of acute inflammation?
Clear apoptotic cells
Produce anti-inflammatory mediators
