Inflammation Flashcards
What is inflammation? What is inflammation designed to do?
Where can inflammation occur?
What types of cells does inflammation involve?
When is inflammation initiated?
Inflammation = protective biological process designed to remove damaged cells & clear threats like infections and toxins.
Where: inflammation can occur in any vascularised tissue
Cells involved: cells at the site of damage + recruited immune cells, chemokines, fluid and molecular components from the circulation.
When: cellular damage (none apoptotic cell death) leads to the release of damage associated molecular patterns (DAMPs) or the body detects pathogen associated molecular patterns (PAMPs).
What is the aim of immune cell recruitment during inflammation?
What is the characteristic pathology of inflammation associated with?
Describe inflammation onset and resolution
What happens to blood vessels during inflammation
The aim of immune cell recruitment to the site of injury is to clear the source of the initial inflammatory signal, and eventual resolution and repair of the inflamed tissue.
Inflammation characteristic pathology: increased fluid and leukocyte numbers + recruitment of innate cells into the damaged tissue.
The majority of inflammation is acute, with rapid onset and resolution.
Blood vessels thicken during inflammation
What happens if the acute inflammatory response can’t remove the inflammatory stimuli?
If the acute inflammatory response can’t remove the inflammatory stimuli then other immune cells - adaptive immune cells - are recruited and a state of chronic inflammation can occur.
What are the four main signs of acute inflammation and why?
What type of response is inflammation to cellular injury?
What is inflammation designed to do?
Rubor (redness) - accumulation of red blood cells due to vascular leakage increasing blood flow into the inflamed tissue.
Calor (heat) - increased presence of fluid at core body temp at a site that would otherwise have limited exposure to this. Infiltrating immune cells are also highly metabolically active.
Dolor (pain) - many of the same mediators that signal to endothelial cells and other immune cells during inflammation also act on noiciceptors. Histamine and prostaglandins (PGEs) released by mast cells and neutrophils drive pain sensitisation in local nociceptor. Macrophages and lymphocytes can also contribute.
Tumor (swelling) - vascular leakage increases blood flow into the inflamed tissue leading to fluid build up.
Functio laesa (loss of function) - fluid build up and immune cell infiltration lead to that area of tissue being unable to carry out its primary function.
Inflammation = non specific response to cellular injury. Designed to remove the cause and consequence of injury.
What are some causes of inflammation (list 6)
- pathogens
- allergens
- auto antigens
- physical damage
- extreme temps
- non apoptotic cell death
What are some diseases where inflammation is observed (list 6)
- infection
- autoimmunity
- hypersensitivity
- trauma
- fibrotic disease
- cancer
List 7 cell types involved in inflammation
Epithelial cells Endothelial cells Neutrophils Lymphocytes Eosinophils Mast cells
Detail the 3 main steps involved in acute inflammation
- Change in local blood flow
- Structural changes in the microvasculature
- Recruitment/accumulation of immune cells and proteins
What happens when there is damage to vascularised tissue? (3 steps)
- Inflammatory signals
- non apoptotic cell death
- detection of foreign material - Vasodilators released
- histamine
- nitric oxide - Vascular changes
- increased permeability
- dilation
- reduced (blood?) flow
- plasma leakage
What benefits does increased vascular permeability and leakage bring to tissues that have been damaged?
What is exudate?
Benefits to increased vascular permeability and leakage of fluid into inflamed site:
-increased: antibodies, protein, barrier and leukocyte migration
Exudate = fluid, proteins and cells that have seeped out of a blood vessel
List soluble mediators released at injury, their principle source and their actions
Mediator: Histamine
Principle sources: mast cells, basophils, platelets
Actions: vasodilation, inc vascular permeability, endothelial activation
Mediator: prostaglandins
Principle sources: mast cells, leukocytes
Actions: vasodilation, pain, fever
Mediator: cytokines (TNF, IL-1)
Principle sources: macrophages, endothelial cells, mast cells
Actions: endothelial activation (adhesion molecules), fever, malaise,
pain, anorexia, shock
Mediator: chemokines
Principle sources: leukocytes, activated macrophages
Actions: chemotaxis, leukocyte activation
Mediator: complement
Principle sources: plasma (produced in the liver)
Actions: leukocyte chemotaxis and activation, vasodilation (mast cell stimulation), opponisation
What happens during immune cell recruitment?
Which type of immune cells are usually the first to be recruited to the site of inflammation?
- recruitment and inflammation signals at the site of damage e.g. chemokines produced
- chemokines diffuse out to form a gradient
- leukocytes expressing complementary chemokine receptors migrate toward the chemokine source
Neutrophils are often the first cell type to be recruited to the site of inflammation.
What are the 4 steps involved in neutrophil extravasation, give details.
- Chemo-attraction
- cytokines cause endothelial up regulation of adhesion molecules (e.g. selection) - Rolling adhesion
- carbohydrate ligands in a low affinity state on neutrophils bind selectin - Tight adhesion
Chemokines promote low to high affinity switch in integrins
LFA-1, MAC-1 enhance binding to ligands. - Transmigration
Cytoskeletal re arrangement and extension of pseudopodia.
Mediated by PECAM interactions on both cells.
What are 3 functions of neutrophils at the site of inflammation?
- Pathogen recognition
- Pathogen clearance
- phagocytosis
- netosis - Cytokine secretion
- recruitment and activation of other immune cells
Detail the process of phagocytosis
- large particles engulfed into membrane bound vesicles - phagosomes
- phagosome fuses with lysosome (vesicles containing enzymes elastase and lysozyme) -> phagolysosome
- reactive oxygen species (ROS) - phagocyte NADPH oxidise
- antimicrobial peptides
