Inflammation

Cytokines, like histamine and leukotrienes, are secreted by damaged cells in Dave’s ankle. How do these cytokines

In the body, occurrences happen to where our bodies find ways to heal itself when indiscriminant things take place. When the body senses an infection or damage tissue leukocyte diapedesis occurs and serves an s a personal repair system. Leukocyte diapedesis is when leukocytes migrate out of the circulatory system and into the location of infection or tissue damage. This operation is a fragment of the innate immune response. This involves the drafting of leukocytes that are not due to any known cause. In order for the leukocytes to flow through the vascular endothelial (lines the entire circulatory system, from the heart to the smallest capillaries), leukocytes must be recruited from the circulation into tissue.

51) What activity does cell 1 undertake to contribute to the body's defense against injury and infection? phagocytosis of foreign materials

Ed’s blood contains white blood cells, which combat infection and inflammation. Foreign invaders attract phagocytic neutrophils and macrophages by means of chemotaxis. These particular cells eat and dispose of pathogens in a process called phagocytosis.

Inflammation normally occurs as a second response when damage tissues. Inflammation can occur immediately however

Neutrophils are the most abundant type. They are known as phagocytes, which means they kill invading germs and disease. When an invasion occurs, neutrophils rush through the walls of the blood vessels from chemical signals.

Overwhelming, deleterious host immune response to an infection due to release of chemicals to fight the infection 2• 1

When an inflammatory response happens white blood cells release endotoxins and exotoxins that destroy the bacteria causing infection. However, these toxins also cause damage to the surrounding blood vessels and therefore leak into the

Fluid building up in the tissues caused by an inflammation response, triggered by the repeated stresses on the tissues, can lead to maceration of the deeper tissues, resulting in wounds and ulcers. Especially in patients with limited healing due to circulation conditions and diabetes, or those suffering peripheral neuropathy (Fig 3)

Step3, Phagocytes engulf dead cells and cellular debris. Step4, Platelets move out of the capillaries to seal the wounded area. The implantation of a biomaterial initiates the inflammatory response in a sequence of events following the implantation from acute inflammation to chronic inflammation to granulation tissue. Acute inflammation lasts a few hours to days. Histamine release and blood vessels near the implantation site become dilated and leaky. Neutrophils and plasma protein “escape” into tissue. Neutrophils are also called poymorphonuclear leucocyte (PMN). Area around the injury becomes swollen and red due to the increase of blood flow. Major role of neutrophils is to phagocytose (engulf and eat dead cells) microorganisms and foreign mateirals. Neutrophils are short lived. Predominate during the first few days of inflammation. Chronic inflammation is the 2nd stage of healing process. Presence of monocytes and lymphocytes. Monocytes differentiate into macrophages to phagocytose particles and break it down into smaller fragments. If the device is large, frustrated phagocytosis will occur where macrophages become larger by fusion and foreign body giant cells will

2003). However, endothelial cells may play a minor role in the transmigration of the inflammatory cells because irradiating these cells in vitro did not upregulate chemokine gene expression (Gaugler et al. 1998). This may also support the notion that the mesenchymal cells of the sinusoidal wall, that is, the hepatic stellate cells, differ from the Thy-1+ mesenchymal cells in the portal vessels and in the portal area (Dudas et al.

The effects of integrin’s vary from the type of protein they are and how they affect a certain part of the body. They are usually surface receptors that will interact with extracellular matrix. There is a family of alpha and beta classes which would usually form heterodimers. They are used for adhesion purposes most of the time and can also transduce a biochemical signal into or out of the cell. This process is called bidirectional, where the can transmit information from in and out of a cell. There are different structures that integrin’s play a role in. Integrin’s can bind to a ligand, where it will form a complex with a biological molecule that will usually serve as a purpose. They can go through a process called activation, where they would have a conformational change of the receptor. They can also trigger a cascade effect, which can change a receptors shape.

An antibody induced complement mediated process results in epithelial detachment. Passive transfer studies in newborn mice have shown that antibodies to BPAg2 induce subepidermal blisters by an inflammatory mechanism. This interaction triggers immunologic events that result in the expression of inflammatory mediators that induce migration of lymphocytes, eosinophils, neutrophils, and mast cells to the BMZ. The separation of epithelium from the underlying tissue within the BMZ results from either direct cytotoxic action or the effect of lysosomal proteolytic enzymes. Passive transfer studies of antibodies against laminin 5 induce noninflammatory subepidermal blisters which indicate that antilaminin 5 IgG is pathogenic, although the mechanism is not clear. Anti α6 Antibody produced separation of epithelium from basement membrane. Fibroblasts also are activated secondary to the

Figure 2 from Lasky (1992) shows the three major steps of inflammation. Step I is the initial low-affinity rolling interaction that is mediated by all three selectins. Step II involved activation of leukocytes that alter concentration gradients of various chemotactic factors. Step III is the high-affinity adhesion, change in shape of leukocyte, and finally extravasation. Figure 2 left out another important factor of selectin’s role in inflammation: PSGL-1. PSGL-1 on the plasma memebranes of neutrophils or monocytes binds to P-selectin translocated to the surfaces of inflamed endothelial cells (Zimmerman 2001). The binding of PSGL-1 by P-selectin is particularly important in the initial steps of inflammation. This intereaction is responsible for the recruitment of inflammatory leukocyte (Ley 2013).

The neutrophils are attracted by fibronectine and growth factors which leads to them performing their role of phagocytosis. Phagocytosis allows the neutrophils to engulf all the debris and bacteria that are in and surround the site therefore getting rid of foreign particles and allow a clean environment for the inflammation to being to happen. As a result of the phagocytosis happening this then leads to macrophages replacing neutrophils which come from immature monocytes which are stored in spleen, they secrete growth factors and cytokines which lead onto the next phase of the healing response which is the proliferation phase (Frederic H. Martni, Judi L. Natch, Edwin F. Bartholomew, 2014).