Inflammation Flashcards
What is the characteristic pathology associated with inflammation
Inflammation is associated with a local higher fluid volume and higher leukocyte number
Why can chronic inflammation lead to tissue damage
Chronic inflammation can cause repetitive rounds of inflammation, tissue damage and repair that eventually result in scar formation and loss of tissue function
What are the five canonical signs of acute inflammation
Rubor (redness), tumor (swelling), calor (heat), dolor (pain) and loss of function
What things can cause inflammation and when is inflammation seen
Infection, physical tissue or cell damage, allergens, self-antigens (autoimmune disease)
Why does inflamed site appear red and swollen
As an inflammatory response, the capillaries at site of infection dilate and permeability increases, so fluid enters the tissue more easily and red because vasculature is closer to skin.
What are the inflammatory signals in external tissue damage
DAMP’s released by non-apoptotic cell death and PAMP’s by pathogens that can infect the damaged site
Which two vasodilator are released by mast cells in response to inflammatory signals
Histamine and nitric oxide
What are the effects in the vessels in response to vasodilators
The endothelial layer of the capillaries become more leaky because of bigger pores between them, causing increased vasopermeability and enlarged blood vessels. This both also reduces blood flow in capillary at inflamed site.
What are four benefits of increased vascular permeability and leakage in inflammation
Chemotaxis and easy migration for leukocytes, antibodies can enter the tissue, increased protein in tissue (for complement system), physical barrier for pathogens
What is the effect of prostaglandins in inflammation and which cells produce them
Prostaglandins are involved in vasodilation, pain and fever and are produced by mast cells and other leukocytes
What are complement proteins used for in inflamed tissue
Complement proteins can be used for opsonisation, for chemotaxis or to directly attack pathogens via MAC. It can also lead to vasodilation by activating mast cells.
What is exudate and what is its function in inflammation
Exudate is the fluid that seeps out of blood vessels with increased vascular permeability and contains fluid, proteins and leukocytes. It functions as a physical barrier for pathogens and contains all proteins and cells needed for both cellular and humoral response
How do leukocyte respond to chemokine gradient
Leukocytes move in the direction of higher complementary chemokine concentration and detect concentration by binding chemokines with complementary chemokine receptors
By what type of receptors binding to CXCL8 are neutrophils recruited to inflammation site
G-coupled transmembrane receptors complementary to IL-8
What is the effect of cytokines on the endothelial layer of near blood vessels
Cytokines stimulate cells of local endothelial layer of capillary to express adhesion molecules on cell membrane such as selectins
What are the four stages of neutrophil extravasation
- Chemo-attraction to inflammation site, 2. rolling adhesion to endothelial wall, 3. Tight adhesion to endothelial wall, 4. Migration through pores between endothelial cells.
Which ligand on neutrophil membrane is important in binding to endothelial selectins
Selectin binding ligands such as PSGL1 or siacyl-Lewis-X
Which kind of adhesion molecules is involved in the tight adhesion of neutrophils
Integrins expressed on neutrophil cell membrane are involved in tight adhesion of neutrophils to endothelial layer, such as LFA1 or MAC1
Which adhesion molecules on endothelial cells are involved in tight adhesion
The ICAM1 receptor on endothelial cells is involved in the tight adhesion of neutrophils to endothelial wall
Which molecules mediate the transmigration of the neutrophils
PECAM molecules on both neutrophil and endothelial cells
What changes intracellularly in neutrophils during transmigration
The cytoskeleton changes and forms pseudopodia that squeeze through pores in endothelial walls
What are the three functions of neutrophils at the inflammation site
Recognising pathogen, attacking pathogen (via phagocytosis and netosis) and cytokine production
What kind of receptors on neutrophils are used to detect lipopolysaccharides from Gram-negative bacteria
Toll-like receptor 4 and CD14 on neutrophil are used to detect LPS
What is netosis and what is used for
Netosis is the formation of extracellular traps for pathogens, consistent of extracellullar fibres of neutrophil DNA and enzymes that break down bacterial components.
What substances do the lysosomes involved in phagocytosis consist of
Lysosomes that fuse with phagosomes contain reactive oxygen species, defensins, lysozyme and elastases
What promotes the switch from low affinity carbohydrate ligands to integrins in neutrophils
A high concentration of chemokines make neutrophil switch low affinity ligands to high affinity integrins for tight adhesion to endothelia vessel wall
What is the vesicle called in phagocytosis when the phagosome and the lysosome fuse
Phagolysosome, which contains pathogens and enzymes that break it down
How is the acute inflammatory response downregulated
Nuetrophils die very quickly after activation and inflammatory cytokines and mediators produced are very rapidly turned over
How do macrophages downregulate the acute inflammatory response
Macrophages produce anti-inflammatory cytokines that inhibit neutrophil activation
What are immunogens
Antigens that induce an immune response without the help of co-stimulatory or additional substances
What are haptens
Antigens, usually small, that induce an immune response when they are bound to a larger molecule which is then recognised by immune system as foreign
What is the difference between acute and chronic or granular inflammation
In chronic or granular inflammation there is a persistence of inflammatory stimuli and there are also inflammatory macrophages, T cells and plasma B cells infiltrated in tissue
What is the key difference between acute and chronic inflammation
In chronic inflammation the inflammatory signal is not cleared and this causes a repetitious cycle of damage and repair
What can cause persistent inflammatory stimuli
Resistant pathogens that fight off or evade immune response, unclearable antigens that cannot be transported away, persistant toxins or allergens that are abundant in environment, self antigens because body will continue to make these in tissues
Which immune cells can be found in the distinct immune infiltrate in chronic inflammation
Inflammatory macrophages, T cells and antibody secreting plasma B cells
What happens to the body tissues in chronic inflammation and what causes this
Chronic inflammation without clearance of pathogens causes bystander damage to tissue, and a repetitious cycle of damage and repair occurs that cause fibrosis and scarring of tissue and subsequently loss of tissue function
How can fibrosis and angiogenesis occur in chronic inflammation
The repair of tissue damaged by bystander destruction in inflammatory response can cause formation of collagen fibres and new vasculature, when damaging process continues these collagen fibres are only thing that remains and this is fibrosis
Why can macrophages be both good and bad in inflammation
Because they can be involved in both inflammatory and anti-inflammatory responses. Its cytotoxicity can be both good and bad, since it can help in an acute immune response against pathogens but also cause tissue damage in chronic inflammation. It can secrete both inflammatory and anti-inflammatory cytokines. It can help with wound repair, but this can also cause fibrosis in chronic inflammation.
What anti-inflammatory cytokine is secreted by both macrophages and T-cells
TGF-β, secreted by both ant-inflammatory macrophages and regulatory T cells
What signal from T cells induces an inflammatory response in the macrophage
IFN-γ, secreted by activated T cell to activate macrophage
How can B cells affect acute and chronic inflammation remotely
B cells can produce antibodies in the lymph nodes which are then transported via the lymph and blood to the site of inflammation where it can bind to specific antigens
What is granulomatous inflammation
Chronic inflammation of distinct location with scarring that forms a granuloma due to localised unclearable pathogen
What is the function of the aggregation of activated macrophages in granulomas
The macrophages form a physical barrier to prevent pathogen from spreading
In what situation would granulomatous inflammation occur
Granulomatous inflammation occurs as a response to highly resistant infectious agents such as mycobacterium or to tumours that try to evade immune response
What can be the sequelae of acute inflammation
It can lead to resolution of the infection, either without damage or with abscess formation or fibrosis. It can also lead to chronic inflammation.
What can be the sequelae of chronic inflammation
In can lead to progressive tissue damage that causes fibrosis and loss of function of that tissue and potentially organ.
What is the result of chronic inflammation in tissue
Chronic inflammation can lead to angiogenesis, scar formation, infiltration of mononuclear leukocytes and progressive tissue damage
What causes scarring after wounds
It can be difficult to remove the collagen network that has been built in wound repair process, this will leave scarring because of collagen fibres at that wound site
How can scarring cause loss of tissue function and organ failure
If cells in tissue are not regenerated after damage, the collagen network cannot carry out this function and this causes loss of function of that part of the tissue or the organ itself
What causes the heat at inflammatory site
In inflammation, exudate fluid originating from the blood that has a higher core temperature than superficial tissues makes superficial tissue warmer, and highly metabolically active leukocytes may add by generating heat.
How can molecules released in acute inflammation lead to pain
In inflammatory response released molecules such as histamine, prostaglandins and interleukins by mast cells and neutrophils and macrophages can induce response in local nocireceptor neurone that transmits pain signals to brain.
How can the exudate cause loss of function in alveoli
Exudate forms physical barrier against pathogen but can also make gas exchange in alveoli less efficient because diffusion is slowed down and this causes loss of function of lung tissue
