Immune responses cascade

A cascade of proteins of the immune response that can be triggered by antigen-antibody complexes and by the innate immune system (e.g. exposure to microbial polysaccharides) to raise the immune response. Complement proteins can detect and bind to foreign material or immune complexes and label them for phagocytosis. They can also cause inflammation by directly degranulating mast cells and releasing chemokines to recruit other immune cells into the affected area. 

The main site of the mucosal immune system in the gut is referred to as gut-associated lymphoid tissue (GALT), which can be divided into inductive and effector sites. In the small intestine, the inductive sites are in the Peyer s patches, which consist of large lymphoid follicles in the terminal small intestine. The contact with external antibodies triggers a series of cascade events in the body based on immune response (Brandtzaeg et al., 1999). 

The second aspect of biocompatibility is a leaching problem. Ion-selective electrode materials, especially components of solvent polymeric membranes, are subject to leaching upon prolonged contact with physiological media. Membrane components such as plasticizers, ion exchangers and ionophores may activate the clotting cascade or stimulate an immune response. Moreover, they can be potentially toxic when released to the blood stream in significant concentrations. 

The complement system which functions as part of the immune response is composed of about twenty proteins which circulate in the blood stream as inactive precursors. The complement cascade is functionally divided into two arms called the classical and alternative pathways, reflecting their different initiating events but which converge at C3. A simplified scheme is shown in Figure 5.25. 

Festjens, N., T. Vanden Berghe, and P. Vandenabeele. 2006. Necrosis, a well-orchestrated form of cell demise Signalling cascades, important mediators and concomitant immune response. Biochim Biophys Acta 1757(9-10) 1371-87. 

The MAPK cascade in the plant s defense against bacterial pathogens is remarkably similar to the innate immune response triggered by bacterial lipopolysac-charide and mediated by the Toll-like receptors in mammals (Fig. 12-30b). Other membrane receptors use similar mechanisms to activate a MAPK cascade, ultimately activating transcription factors and turning on the genes essential to the defense response. 

Two immunization procedures designed to enhance the immune response to multiple antigen mixtures have been reported recently. The cascade immunization technique (20) utilized in vitro depletion of E. coli proteins (ECPs) which had previously elicited an antibody response. The removal of these dominant immunogens from the mixture was accomplished by immunoabsorption with antibodies obtained from an earlier antiserum. The passive immunization procedure (21) relied on in vivo blocking of strong immunogens by the concurrent administration of early antiserum obtained previously. This latter report demonstrated the presence of an apparently poorly immunogenic ECP to which a humoral response could only be elicited by this passive procedure. 

Figure 3. Selection of ECP subpopulations forjprogressive iterations of the cascade procedure by silver stained SDS-PAGE. Lane 2 in each panel shows the entire ECP mixture used as the column load and lane 3 shows the column flowthrough fraction used for the next injection. Panel A demonstrates the affinity chromatography performed with day 14 antisera, Panel B with day 28 antisera and Panel C with day 42 antisera. The arrow shows ECPs depleted by the early antibodies. The progression of the immune response is clearly apparent although it is clear not all of these proteins are equally immunogenic. A 50 Kd protein has saturated its respective antibody and begun to flow through the column (Panel C, lane 4). Reproduced with permission from Ref. 24. Copyright 1989 The Humana Press Inc.

These data suggested that a mechanism of early priming of the immune response though the cascade procedure resulted in a broader spectrum of antibody reactivity. This improvement also required additional time (56 days) and/or subsequent injections of the total antigen mixture because similar experiments with day 56 antisera demonstrated equivalent antisera reactivity (24). 

A series of proteins collectively called the complement participate in the immune response to the entry of foreign cellular or viral material into the organism. This group of proteins consists of about 20 entities, some of which are enzymes. Complement was first associated with the lysis of foreign red blood cells in the nineteenth century it also participates in the lysis of bacterial cells. The complement activation cascade, very similar to the blood coagulation cascade, involves the stepwise activation, via proteolysis, of various components of the complement system until a final protein complex, the membrane attack unit (also called the C5b-9 complex), is generated. It then punches holes in the membrane to which it is bound. 

In addition to the effect of increased VLCFA on membrane and possibly cellular function, the rapid cerebral form of X-ALD is characterized by an inflammatory response that is believed to contribute to the demyelination that characterizes this phenotype and which is similar to that seen in multiple sclerosis. These cerebral lesions are characterized by breakdown in myelin with sparing of the axons accompanied by the accumulation of cholesterol ester in the neurons. A perivascular inflammatory response with infiltration of T cells, B cells, and macrophages also is present. Therefore, it is believed that the rapid cerebral disease has an im-munologically-mediated component. It has been suggested that the inflammatory response occurs in response to the elevated levels of VLCFA in lipids, which elicits an inflammatory cascade that may be mediated in part by cytokines. Once this cascade begins, it may be more difficult to intervene in the disease process, and in general therapeutic interventions studied to date have been most effective when initiated early. Therefore, prevention of the initiation of the immune response is important for improving outcome. 

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