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COMMON PATHWAYS
(including extracutaneous routes)
Not all cell mediated immune reactions are confined to the reactive superficial unit. In one dermal variant, inflammatory cells are confined to the perivenular spaces of the reticular dermis. These latter patterns,
if seen in experimental models of cell mediated immunity, qualify as the perivenular islands of experimental pathology. In the perivenular infiltrates, which characterize perivenular islands, lymphocytes and
histiocytes may extend from perivascular spaces into the reticular dermis among the collagen bundles (i.e., lymphohistiocytic collagenosis). In perivenular islands, histiocytes often are a prominent feature. Some
perivenular, lymphohistiocytic reactions show thrombosis and necrosis of the affected vessels; they manifest angiocentricity with occlusion of some of the vessels.
Humoral immune reactions are manifested morphologically by infiltrates of inflammatory cells; the locus, that is selected, relates to ecotatic influences from sites in which either antigens are exposed, or immune
complexes have found egress from the circulation into tissue. The complexes may form in the circulation but, in certain selected sites, they leak into the interstitial tissue to induce alterations that are immune
mediated. Although humoral factors may initiate an immune response, the common response is, in varying degrees, cellular.
In most immune mediated disorders, the immune reaction, once initiated, is mediated at a cellular level, and commonly is manifested in an interplay between the antigens of antigen-bearing sites, and lymphocytes and
histiocytes. In the process, T lymphocytes are activated and, in turn, are attracted to sites of tissue damage. In some examples, neutrophils are also represented in the infiltrates. The antigens may be native, but
altered, components of cells, or they may be components of the supporting connective tissue. In addition, the character of endothelium is altered in a manner which promotes the egress of lymphocytes through defects
in the endothelial layer (particularly the endothelium of post-capillary venules [i.e., among “high” endothelial cells]). In the altered kinetics of intravascular homeostasis, the endothelial layer may be damaged,
and the clotting process initiated; the results may include thrombosis and fibrinoid necrosis of vessels in the immediate vicinity of the immune response. These alterations may compromise the integrity of the local
blood supply, and produce ischemic damage of tissue; if the affected vessel is sizable, the area of necrosis may be wedge-shaped.
The leakage of fluids into the sites of inflammation, and the response of lymphatics to a local increase in kinins promotes a increased flow of lymph. In the lymph, products of inflammation, such as cellular debris,
products released by damage to connective tissue, and kinins find their way from the site of inflammation to the regional lymph nodes. If organisms have a role in the inflammatory process, they too may find their
way to regional lymph nodes. All these products on reaching the lymph node activate lymphocytes.
The cellular kinetics of an immune mediated response are antigen specific in regard to humoral processes, and site specific in regard to cellular responses. Germinal centers of lymph nodes are pivotal in providing
new generations of B lymphocytes. As these new generations cells move from the germinal centers, some become memory cells dedicated to an antigen specific response, but held in reserve. Some are committed to
terminal differentiation; they become plasma cells, and produce antibodies which are specifically structured to react with antigens of a particular type. The antibodies are carried in lymph to the circulating blood.
In the paracortical zones of the activated lymph nodes, T lymphocytes are stimulated to proliferate; they are activated. They, in sequence, find their way into sinusoids, into lymphatics, and thence into the blood
stream. Finally, on arrival in a site of inflammation, they, in concert with histiocytes and, depending on the nature of the injury, with neutrophils, contribute to the population of inflammatory cells in the sites
of injury. In either humoral or cellular immune reactions, most of the histiocytes in inflammatory infiltrates are KP-1 (CD68) + monocytes; once activated, they become phagocytes. Some histiocytes (dendritic type)
are residents of the dermis; they modulate reactions of fixed mesenchymal cells; these dendritic forms are factor XIIIa +. Some of the dendritic histiocytes are found in both the dermis and the epidermis. They too
are a component of the system of dendritic histiocytes; in the epidermal domain in response to injury, dendritic histiocytes may acquire the capacity to collect antigens on their surfaces, and to then present the
antigen to migratory, activated (transformed) T lymphocytes. Dendritic histiocytes of the epidermis, that are dedicated to antigen presentation, are immunoreactive for antibodies to S-100 protein and CD1a. In the
epidermis, or the dermis, some of these dendritic histiocytes contain distinctive organelles, the Birbeck granules.
In defining relationships between initiating factors, cell types, and selected sites, the histology of inflammatory diseases of the skin must also be compartmentalized. Histologically, the compartmentalization of
inflammatory diseases is not a random act. Each compartment can be characterized by a variety of features; the features reflect a variety of factors, the most important of which have to do with sites of preference
for the localization of antigens or complexes. If cells cluster in the epidermis, then most likely the offending antigens are similarly distributed. If the epidermal response is lymphohistiocytic, then close
attention to the relationships between histiocytes, keratinocytes, and lymphocytes may provide guides as to the basic nature of the process.
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