Schistosome Egg Granuloma in Human Liver
The egg induced granuloma formation is a Delayed Type Hypersensitivity (DTH or Type IV Hypersensitivity) reaction, and, although eventually resulting in severe pathology, appears to be a necessary protective host response against hepatotoxic components of Soluble Egg Antigen (SEA), secreted by the entrapped egg. The granuloma that forms around the egg consists mainly of a number of different type of immune cells, including both T and B lymphocytes, macrophages, giant cells, epitheloid cells, mast cells, plasma cells, fibroblasts and Eosinophils. These cells all play a significant role in the formation of the granuloma as they interact with each other in a highly complex fashion, both by direct cell to cell interactions, but more commonly through the interaction of a wide variety of cytokine chemical messengers. However, for simplicity, known cytokine interactions will not be detailed and only three cellular components will be considered here. It is important to note that these cellular responses are dynamic processes, and different cellular responses are important at different stages of granuloma formation.
The Macrophage. These Mononuclear cells take up the SEA secreted by the entrapped egg. Subsequent antigen presentation by these macrophages leads to expansion and activation of populations of antigen specific MHC class II-expressing cells within the growing granuloma, and also secreting lymphokines attracting other immune cells to the growing granuloma.
T Lymphocytes. Examination of liver granulomas has shown that between 10 - 15% of the inflammatory cells are T lymphocytes. These have a profound influence of the formation of the granuloma, and may be functionally divided into two groups, cells expressing the surface antigen CD8 (CD8+ve lymphocytes), and cells expressing the surface antigen CD4 (CD4+ve lymphocytes).
a) CD4+ve cells - These may in turn be subdivided into two groups in terms of their activity, cells exhibiting a so-called Th1 type response, and cells exhibiting a Th2 type response. CD4 cells appear to have a more central role in the formation of the granuloma compared with the CD8+ve lymphocytes, and act under the influence of the antigen presenting macrophages, stimulating specific antibody responses to SEA, the exact nature of which will depend on whether a Th1 or Th2 type response is in operation.
b) CD8+ve cells - These may again be subdivided into two groups on the basis of their activities, T suppressor effector cells (Ts), and cytotoxic cells (Tc). In the granuloma it appears that the Ts cells down regulate the activity of the CD4+ve cells, modulating the effect of these cells on granuloma growth.
The Fibroblasts. These are not strictly immune cells, but are acted on by cells of the immune system, and play an important role in the schistosome egg granuloma. During the late stage of the granulomas formation they in fact replace most of the other cells. They are stimulated both chemotacticaly and to proliferate, by factors produced by the schistosome egg, but more importantly by cytokines secreted by macrophages and CD4+ve T lymphocytes. These fibroblasts mediate collagen deposition in the granuloma, leading to the fibrosis that will eventually result in the hepatosplenic disease associated with schistosome infections.