Immune suppression mechanisms

Commensal or environmental fungi that are typically harmless can become invasive mycoses when the host immune defenses are impaired. Host immune suppression and risk for opportunistic mycoses can be broadly classified into three categories (1) quantitative or qualitative deficits in neutrophil function, (2) deficits in cell-mediated immunity, and (3) disruption of mechanical/and or microbiologic barriers. 

Kerkvliet, N. and Brauner, J., Mechanisms of 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD)-induced humoral immune suppression Evidence of primary defect in T cell regulation, Tox. Appl. Pharmacol., 87, 18, 1987. 

As mentioned above, PAF and PAF-like molecules are rapidly synthesized by keratinocytes following UV exposure. We suggest that two mechanisms are involved. UV-induced free radical formation leads to membrane oxidation and the formation of oxidized phosphatidylcholine. The PAF-like molecules bind to PAF receptors in either a paracrine or autocrine fashion. This induces the release of arachidonic acid from the membrane, activates PI.A2 and promotes the synthesis of bona fide PAF.55 The newly synthesized PAF then binds to PAF receptors, which upregulates the production of more PAF and downstream biological modifiers such as eicosanoids and cytokines. Ultimately this activates the cascade of events that leads to immune suppression. 

Taylor A, Verhagen J, Blaser K, Akdis M, Akdis CA Mechanisms of immune suppression by interleukin-10 and transforming growth factor- the role of T regulatory cells. Immunology 2006 117 433-442. 

The monoclonal antibodies used as immunosuppressive agents in tissue transplantation include muromonoab-CD3, daclizumab and basiliximab. Muromonoab-CD3 binds to a specific site on CD3 receptors and interferes with the ability of the TCR to bind the antigen and also inhibits CD3 receptor-dependent signal transduction mechanisms, all of which result in immune suppression. Both daclizumab and basiliximab are monoclonal antibodies directed against IL-2 receptors and consequently inhibit IL-2-dependent responses after tissue transplantation, resulting in immune suppression. The monoclonal antibodies used as immunosuppressive agents are described in detail in Chapter 5. 

Even a cursory review of the pertinent literature leaves the reader in little doubt that cestodes can subvert host immune responses by mechanisms that vary from membrane fluidity (i.e. membrane turnover) (Taylor et al., 1997) to active immunomodulation thatfavours development of immunosuppressive/immunoregula-tory cells (Dai and Gottstein, 1999) and/or an immune-suppressed environment. In this respect the cestode is no different than other helminth parasites. However, the data are fragmented, often quite vague and confused by the specificity of the host-parasite interaction. Therefore we have opted to provide the reader with tabulated data on some of the main findings illustrating cestode manipulation of their... 

Experimental studies in laboratory rodents have demonstrated that a diverse array of chemical exposures suppress immune function (Table 19.2). In addition a limited number of clinical and epidemiologic studies have reported suppression of immune function and/or increased frequency of infectious and/or neoplastic disease following exposure of humans to some of these agents. From the description above it is clear there are a number of cellular and molecular targets for chemicals that act as immunosuppressants. Clearly, a chemical that disrupts cell proliferation would affect clonal expansion. Disruption of T cell maturation in the thymus is another potential mechanism for immune suppression. Chemicals may also interfere with receptor ligand binding at the cell... 

In lymphoproliferative disease, sensory-motor neuropathy may be a result of diffuse malignant nerve infiltration or immune-mediated mechanisms [120], Syndromes similar to Guillain Barre syndrome sometimes occur among patients with lymphoproliferative disease, but in this group, it is uncertain whether cancer by itself favors the development of Guillain-Barre syndrome by suppressing immunosurveillance mechanisms [121]. 

Irwin M (1994) Stress-induced immune suppression Role of brain corticotropin releasing hormone and autonomic nervous system mechanisms. Adv Neuroimmunol 4 29-47. 

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