L7, inflammatory responses

Question 1

the effects of inflammation are characterized by…

Answer 1

increased vascular dilation and permeability
cellular recruitment
cellular proliferation
metabolic changes

Question 2

vasodilation are caused by

Answer 2

inflammatory mediators (ex. cytokines)

Question 3

in inflammation, how is adhesion displayed?

Answer 3

leukocytes attaching to the endothelium

Question 4

what is extravasation?

Answer 4

blood cells, i.e., leukocytes, exiting the bloodstream

Question 5

vasodilation and increased permeability cause…

Answer 5

redness, heat, and swelling

Question 6

why does blood clotting occur?

Answer 6

to prevent spread of infection, occurs in the microvessels

Question 7

how are immune cells recruited to the site of inflammation?

Answer 7

1. tethering: resident tissue cells produce cytokines, chemokines, and other mediators. cytokines and chemokines then activate the cells lining the nearby blood vessels (the endothelium). the activated endothelium cells then express molecules on their surface adhesion molecules and additional chemokines. immune cells tethered to the endothelial cell is mediated by selectins binding to their ligands mucin-like cell adhesion molecules (CAMs)
2. Rolling: occurs once leukocytes are successfully tethered, i.e., the leukocytes are in close contact with the endothelium. the leukocytes roll along the endothelium due to blood flow and weak interactions between selectins and their ligands. rolling allows cells to slow down.
3. Activation: chemokines bind to specific receptors and further activate leukocytes inducing a conformational change of another class of adhesion molecules - the integrins. upon activation, the integrins switch to a high affinity conformation
4. Adhesion: the cell firmly adheres to the endothelium. integrins bind their ligands located on the endothelium, causing a firm adhesion which flattens out the leukocyte to allow it to eventually exit the vessel.
5. Transmigration: adherent leukocytes squeeze between endothelial cells to enter the tissue below (the site of inflammation). once the leukocytes leaves, the blood vessels reseal immediately and there is no leakage of plasma during the extravasation process. once out of the vessels, leukocytes continue to follow the initial chemokine gradient created by the sentinel cells to find the site of infection

Question 8

describe concept of specificity in leukocyte recruitment

Answer 8

different immune cell types express different adhesion molecules and different chemokine receptors. this recruits the appropriate cells according to context

Question 9

what are the local effects of inflammation?

Answer 9

vascular dilation causing heat and redness, expression of adhesion molecules which recruits leukocytes, vascular leakage causing swelling and pain, and clotting which blocks vessels to prevent the spread of pathogens

Question 10

what are the systemic effects of inflammation?

Answer 10

fever, increased cellular proliferation and mobilization from the bone marrow, increased plasma protein production by the liver, etc.

Question 11

what are systemic effects of cytokines?

Answer 11

1. liver producing acute-phase proteins to activate complement opsonization
2. bone marrow endothelium conducting mobilization which leads to phagocytosis
3. hypothalamus causing an increase in body temperature, fat and muscle inducing protein and energy mobilization to allow increased body temperature. both lead to a decrease in viral replication and increased antigen processing and specific immune response
4. dendritic cells stimulating migration to lymph nodes and maturation, initiating adaptive immune response

Question 12

how do systemic effects influence cellular activity?

Answer 12

increase in opsonization and increase in phagocytosis

Question 13

when is inflammation not a good thing?

Answer 13

when there is excessive inflammation that could lead to: reduced blood flow to vital organs, blood vessel clotting, tissue damage, organ failure, and death. could also lead to chronic inflammation and autoimmune diseases

Question 14

what is the appropriate inflammatory response?

Answer 14

1. limited and localized inflammation
2. containment and removal of pathogen
3. no or limited damage to tissues
4. adaptive immunity activated

Question 15

what are some of the diverse causes that leads to chronic inflammation?

Answer 15

1. unresolved infection
2. dysbiosis (changes in the microbiota)
3. dysregulation of cytokine expression
4. genetic predispositions or mutations (ex. cancer)