lecture 3-4

• Inflammation is the reaction of living tissues to injury.
• Inflammation is highly organized, involving many cell types and signaling molecules.
• Cells and fluid are released from the site of injury during inflammation.
• The 3 major cells in inflammation are neutrophils, monocyte (macrophage), and platelets.
• The 4 classic signs of inflammation are heat, redness, swelling, and pain.
• Sometimes a 5th sign of inflammation is loss of function.
• In the sequence of events of inflammation, the first step is infection or injury.
• Cells detect the injury and release mediators during inflammation.
• Mediators alter blood vessels, which attracts leukocytes during inflammation.
• During inflammation, there is an increase in permeability, causing an exudate of fluid and proteins to leave the vasculature, causing edema and swelling.
• histamine is a mediators that increase during inflammation, causing an increase in permeability of venules.
• Histamine is released from mast cells due to pressure.
• Mast cells surround the venules during inflammation.
• Permeability change can be transient, sustained, or delayed prolonged during inflammation.
• Normally, small amount of blood flowing, but if there is inflammation, there is vasodilation of the arteriole, which cause increase of blood flow.
• hyperemia is the increased blood flow to the tissues, which causes the tissues to become red during inflammation.
• Normally, there is constant fluid exchange: most of the transudate that comes out of the arteriole side of the capillary goes back in the capillary at the venous side
• transudate is the loss of fluid from the blood into the tissues of the body
• exudate is a fluid containing proteins that is released from the circulation, usually containing plasma proteins.
• edema is the swelling of tissues due to excess fluid accumulation
• in mild inflammation, only the permeability of the venules is affected, but in severe inflammation, the whole microcirculation is affected.
• Leukocytes are formed in the bone marrow, where there are stem cells that differentiate into the different types of leukocytes.
• Signalling molecules can go in the bone marrow to change the relative concentrations of the different types leukocytes depending on the situation.
• Neutrophils are essential for inflammation and immunity.
• Neutrophils have multiple roles on multiple cell types, including degranulation, phagocytosis, and neutrophil extracellular traps (NETS) which trap bacteria.
• Macrophage's precursors are in the bone marrow (called monocytes in the circulation).
• There are different specialized types of macrophages in the different tissue types.
• Macrophages can synthesize molecules affecting antibacterial/antiviral defense, blood clotting, cell growth, vascular growth, tumor growth, and collagen production.
• Macrophages functions include:

  • Phagocytosis of bacteria
  • production of inflammatory mediators
  • synthesis of molecules affecting many things
  • initiation of the immune response
  • cleanup operation (scavenging)
• Margination is a phenomenon where RBCs tend to clump and WBCs tend to stick to the sides of the venule.
• Selectins are expressed on endothelial cells, allowing WBCs to stick and roll on the sides.
• Sticking together takes some time since neutrophils need to express the selectin ligands.
• The bond between neutrophils and endothelial cells is not strong, but it slows down their movement and allows them to be in contact with the endothelium.
• Integrins are expressed on the cell surface, allowing neutrophils to stick to the endothelial cell and stop them from moving.
• Neutrophils attach, then migrate out of venules.
• Some of the neutrophils emigrate out of the venule and go to the site of injury, a process called transmigration.
• Transmigration is possible due to other adhesion molecules that are on the edges of the venules.
• Neutrophils also secrete collagenases to help them make their way through the basement membrane.
• White blood cells know where to go when released as they are attracted to a chemoattractant (chemokines) that is released at the site of injury, a process called chemotaxis.
• specific chemokines recruit specific cells.