The inflammatory response (Figure 3.1). a. Tissue resident macrophages: The bacteria in the wound are immediately recognised as by the tissue resident macrophages. -- > they function as an early detection/warning system against invading pathogens. The endothelial cells that line the blood vessels have tight junctions. Macrophages sense danger by recognizing pamps b. A phagocytic pattern recognition receptor (PRR) would bind to a structure on the bacterium to trigger phagocytosis. c. A Toll-like receptor (TLR) would bind to pathogen-associated molecular pattern (PAMP); the interaction initiates a signaling cascade that results in the activation of a transcription factor called NF-KB. d. Alarm cytokines and chemokines: NF-KB activation results in the transcription of genes encoding tumor necrosis factor alpha (TNF-a), Interleukin-1 (IL-1), and Interleukin-6 (IL-6). They are called pro- inflammatory cytokines because they promote the inflammatory response. " Cytokines are molecules that when they bind to a receptor, they give instructions for the cell. In this case the instructions are to change gene expression · TNF-a: · IL-1: helps to increase production of neutrophils in bone marrow · IL-6- acts to produce fever. " Chemokines are a chemoattractant, they generate a gradient that helps neutrophils and monocytes to bind pathogens · CXCL8 or IL-8 is a chemokine that acts as a chemoattractant to guide recruited phagocytic cells to the site of infection. e. Inflammatory response: The inflammatory response at the site of infection is initiated by tissue-resident macrophages and tissue- resident mast cells. Upon injury to the tissue, mast cells release histamine and other inflammatory molecules. Histamine causes blood vessels to dilate, thus increasing blood flow to the area and resulting in the redness and heat association with inflammation. o Pain comes from irritated nerve endings and an increased flow of blood and swelling the puts additional pressure on nerve endings. The accumulation of fluid in the tissues causes the swelling and pain associated with inflammation.
o Redness from the increased number of red blood cells o Increase in temperature bc blood that comes from core of the body is warmer than blood that comes from extremities f. More permeable veins: The cytokines released by the macrophages also act of the blood vessel walls, increasing the permeability of the blood vessel allows components of the blood to leak into the tissue, including fluid, complement proteins, coagulation proteins and antibodies, and cells such as neutrophils and monocytes. They also induce the expression of particular adhesion molecules on the surface of the endothelial cells lining the blood vessel to act as a break to slow down the cells inside the vein and allow them to leak. g. Extravasation: The adhesion molecules allow leukocytes such as neutrophils and monocytes to stick to the endothelial cells of the blood vessel and then squeeze through the spaces between the endothelial cells of the blood vessel and into the tissue. This process is known as extravasation. h. IL-8 gradient: The macrophages provide the CXCL8 gradient which guides the neutrophils, monocytes and dendritic cells to location of the bacteria