During an immune response, often a set of processes occur that create a condition known as inflammation. These processes include many of the innate effector mechanisms we have been discussing. But also some additional events occur as well. Here we pull together the various processes that collectively are called inflammation.
Inflammation is divided into acute inflammation, which occurs over seconds, minutes, hours, and days, and chronic inflammation, which occurs over longer times.
Acute inflammation begins within seconds to minutes following the injury of tissues. The damage may be purely physical, or it may involve the activation of an immune response. Three main processes occur:
The first two of the above effects are readily visible within a few minutes following a scratch that does not break the skin. At first, the scratch is visible as a pale red line. Then the surrounding few millimeters of tissue on both sides of the scratch becomes red as blood flow increases locally. Finally, the area swells as additional fluid accumulates in the interstitial spaces of the region, a condition known as edema. The increased permeability of the capillaries occurs because the endothelial cells separate from one another at their edges.
As described when we were discusssing the migration of neutrophils from blood vessels into the tissues, the first step is the binding of the neutrophils to the endothelium of the blood vessels. The binding is due to molecules, called cell adhesion molecules (CAMs), found on the surfaces of neutrophils and on endothelial cells in injured tissue. The binding occurs in two steps. In the first, adhesion molecules called selectins lightly tether the neutrophil to the endothelium, so that it begins rolling along the surface. In a second step, a much tighter binding occurs through the interaction of ICAMs on the endothelial cells with integrins on the neutrophil.
The figure below is the same as that on the earlier page describing the recruitment of neutrophils.
In this light micrograph of a blood vessel in the lungs you can see a layer of neutrophils adhering to the inner surface of the blood vessel. (Recall that a neutrophils can be identified by its nucleus, which is divided into several lobes. Note that the histology stains used in this picture and the next are not the same as was used for the blood slide in lab.)
Notice in the above micrograph that you can also observe neutrophils outside as well as inside the blood vessel. Once bound to the endothelium, neutrophils squeeze through gaps between adjacent endothelial cells into the interstitial fluid, a process called diapedesis.
Sometimes pus forms at the site of acute inflammation, especially if a foreign body is present to continually aggravate the tissue. This light micrograph of pus from an inflammed appendix shows that pus is packed with neutrophils, the primary cells typically present during acute inflammation. (How can you tell these are neutrophils?)
Once outside the blood vessel, a neutrophil is guided towards an infection by various diffusing chemotactic factors. Examples include the chemokines and the complement peptide C5a, which is released when the complement system is activated either via specific immunity or innate immunity.
However, in some circumstances eosinophils rather than neutrophils predominate in acute inflammation. This tends to occur with parasitic worms, against which neutrophils have little success, or with a response involving the antibody IgE. Eosinophils release several proteins, such as major basic protein, which are often effective against parasites. Eosinophils also release several regulatory molecules that increase endothelial permeability. Note that eosinophils are also linked to certain types of allergies.
What causes the characteristic sequence of events in acute inflammation? Various cells at the site of tissue damage or of a specific immune response release regulatory molecules that act locally as paracrines.
QUESTION: What types of molecules trigger inflammation?
QUESTION: Name some cells that release the above molecules.
QUESTION: What is complement C5a?
QUESTION: What change caused by inflammatory paracrines results in edema in the affected area?
QUESTION: Suppose tissue damage triggers the release of a prostaglandin that causes inflammation in the area. What specific molecule does the tissue damage activate that starts the synthesis of the prostaglandin?
QUESTION: Scroll up through the figures on this page, briefly describing what you see and why.