Full text loading...
Chapter 11 : Experimental Models of Superantigen-Mediated Neuropathology
Category: Bacterial Pathogenesis; Immunology
Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase
There have been different attempts with superantigen to modify experimental allergic encephalomyelitis (EAE), which is taken as an animal model for multiple sclerosis (MS). MS is not simply an inflammatory disease like EAE. It is well established that in MS chronic degeneration runs in parallel to outbreaks of inflammation. The portions of inflammation and degeneration may vary so that different types of disease course can be distinguished. Recent studies indicate that the degenerative process MS is not always secondary to but may also precede neuroinflammation. The chapter presents experiments which demonstrate that superantigen expressed in the brain or spinal cord is capable of inducing neuroinflammation as in MS. Horizontal sections of the cerebral hemispheres at the corpus callosum and at the level of the lateral ventricles were stained with hematoxylin/eosin. It is well known that relapsing-remitting MS patients with frequent relapses progress faster than patients with less frequent relapses. HLA associations identified in patients with a relapsing-remitting course of MS may be due to major histocompatibility complex (MHC)-specific binding properties of T-cell superantigens. Different so-called autoimmune diseases involve nerves or muscles. Pathogens like bacteria or viruses are involved in part of them. Although it is likely that true autoimmune phenomena following molecular mimicry are of pathogenetic relevance in some of these diseases, it seems possible that superantigens are involved in parallel or alone in a subgroup of patients with autoimmune neuritis or myositis.
The figure illustrates the effects of intracerebral superantigen alone. Frontal sections of the rat brain at the level of the corpus callosum (cc), hematoxylin and eosin stain. The interhemispheric cleft has been marked by a star. (A) Five days after intracerebral SEA (bar, 1 mm). (B) Part of A at higher magnification. (C, D) Seven days after intracerebral SEB injection (SEB does not activate T cells in rats) and 4 days after intravenous ConA-blast injection; no reactive vessels are observed. The injection canal is surrounded by a few brownish macrophages, presumably containing blood degeneration products.
Each data point represents the mean value obtained from at least two animals. All data sets were supplied with a linear fit. (a) The number of reactive blood vessels per tissue section rises linearly with the number of activated splenocytes injected intravenously. (b) The number of vessel cuffs on representative brain sections is displayed over the SEA concentration. SEA per se, open upward triangles; SEA plus ConA blasts, open circles (see text).
Gene expression of superantigen encephalitis (amplified by 107 ConA-blast i.v.) in CNS 7 days after SEA injection, at least 2-fold increase