Inflammation Flashcards
What are the three main components of acute inflammation?
- Increase in blood flow via vasodilation
- Increased permeability of vasculature
- Activation of leukocytes and plasma proteins to eliminate infection
What are the cells that initiate the inflammatory response? How do they initiate it?
Phagocytes and guard cells
- Release of cytokines (TNF, IL-1) and lipid messengers to recruit leukocytes
- Release of histamine causing vasodilation and increased blood flow to infected area (edema, erythema)
How does vasodilation/increased permeability to affected area occur?
- Vasodilation causes increase in pressure in capillaries
- > Endothelial cells contract due to histamine, bradykinin, leukotrienes
- > Protein/particle leakage to interstitial space
- > Plasma follows particles into interstitial space to equalize osmotic pressure
How do leukocytes transport from blood vessel lumen to site of injury?
- Margination, rolling, and adhesion of leukocyte to endothelial wall
- Migration across wall
- Migration to injury site
Margination, rolling, and adhesion process?
- Margination: stasis of blood -> leukocytes closer to endo wall
- Rolling: L-selectin and ligands for E- and P-selectins on leukocytes interact with receptors/ligands on endo wall
- Adhesion: Chemokines (bound to proteoglycans) on endo wall adhere to leukocytes integrins
What are the receptors and ligands on the endothelial cell wall involved in leukocyte rolling?
E-selectin, P-selectin, ligand for L-selectin
What are the chemical mediators involved in getting E-selectin and the ligand for L-selectin expressed on the endothelial cell wall? What cells release these mediators?
- TNF and IL-1 (from guard cells and macrophages)
- Chemokines
What are the chemical mediators involved in getting P-selectins expressed on the endothelial cell wall? What cells release these mediators?
Thrombin and Histamine
What are the surface molecules on leukocytes that are involved in rolling and adhesion to endothelial cell wall?
- Ligands for E- and P-selectins
- L-selectin
Why do leukocytes roll along the endothelial cell wall? Why do they adhere to the cell wall?
- They roll b/c the selectin adhesions are weak
- They adhere because the chemokines bound to the proteoglycans increase affinity of ICAM-1 on endo cell wall for the integrins (strong bond) of the leukocytes
What immunoglobulins are involved in migration of leukocytes across the endo cell wall?
CD31 or PECAM-1
What is chemotaxis?
- How leukocytes travel to infection site
- Following chemotactic gradient of chemokines and other chemoattractants
What are the dominant leukocyte type in the first 6-24 hours?
Neutrophils (short-lived, react more rapidly to chemokines)
What are the dominant leukocyte type in the next 24-48 hours?
Monocytes (live longer, proliferate in tissues)
What do leukocytes use to degrade microbes after phagocytosis?
NO, lysosomes, reactive oxygen species (ROS)
