V-region-related and -unrelated immunosupression accompanying infections

Abstract

This paper discusses current evidence for the relationship between polyclonal lymphocyte activation, specific immunosuppression with decreased resistance, and autoimmune pathology, that are all often found associated with infections by a variety of virus, bacteria and parasites. The central question of class determination of immune effector activities is considered in the context of the cellular targets for nonspecific mitogenic activities associated with infection. A model is presented to integrate these findings: mitogens produced by the microorganism or the infected cells are preferentially active on CD5 B cells; the resulting over-production of IL-10 will tend to bias all immune activities into a Th2-mode of effector functions, with high titers of polyclonal antibodies and little or no production of gamma IFN and other "inflammatory" lymphokines that often mediate resistance. In turn, these conditions allow for parasite persistence and the corresponding long-term disregulation of self-directed immune reactivities, resulting in autoimmunity in the chronic phase. This model would predict that selective immunization with the mitogenic principles involved in deregulation, could stand better chances than strategies of vaccination based on immunopotentiation against other, functionally neutral antigenic epitopes. It is argued, however, that the complexity of immune responses and their regulation, together with our ignorance on the genetic controls of class-determination, offer poor prospects for a scientifically-based, rational development of vaccines in the near future. It is suggested that empirically-based and technologically developed vaccines might succeed, while basic scientific approaches are reinforced and given the time to provide a better understanding of those processes.

Streptococcus agalactiae GAPDH Is a Virulence-Associated Immunomodulatory Protein

“…In addition, several microbial extracellular proteins including enzymes have also been described as B cell activators (8,13,25,51,52). The ability of microbial constituents to induce polyclonal B cell activation in the infected host constitutes a mechanism of host immune evasion used by pathogens to suppress the specific, potentially protective, immune responses (5,14,21). Therefore, GAPDH-induced B cell activation may represent a mechanism facilitating S. agalactiae survival within the host.…”

“…These effects induced by VIP might contribute to pathogen evasion from the host immune system (5,12,21). Previous reports showing that immunization against a particular VIP confers protection against the infection caused by the VIP-producing microbe, further indicates the important role of VIP for the success of microbial colonization (11,(22)(23)(24)(25).…”

“…It has been described that extracellular proteins produced by diverse pathogenic microbes facilitate microbial colonization through modulation of the host immune system (5)(6)(7)(8)(9). These proteins were thus designated as virulence-associated immunomodulatory proteins (VIP) (10,11).…”

A 24 000 MW Trypanosoma cruzi antigen is a B‐cell activator

“…The single injection of rTc24 without any adjuvants induces the production of immunoglobulins that are not specific for parasite antigens, as described for other mitogenic products released by several micro‐organisms responsible for bacterial, viral, or parasitic infections. 5,33,34 A classical example of these findings is the polyclonal B‐cell activation with absent specific recognition observed after injection of Lipid A. 30,35,36 More importantly, preliminary results suggest that previous injection of rTc24 protein to naive mice is responsible for low lymphocyte responses to heterologous stimulation with sheep red blood cells (SRBC) or with KLH antigens in vivo and to concanavalin A (Con A) proliferation in vitro (data not shown).…”

How Rheumatoid Arthritis Can Result from Provocation of the Immune System by Microorganisms and Viruses

“…Microbial molecules can directly induce proliferation and differentiation of T- and B-lymphocytes regardless of their antigen specificity. In the model of murine Trypanosoma cruzi infection, it was shown that the number of high rate immunoglobulin secreting cells of both IgM and IgG classes increased up to 100 fold each and a variety of effector T cell activities were revealed, with both Ab and cellular immune reactions being predominantly non-specific ( Arala-Chaves et al, 1992 ). Similar observations have been recorded in various viral, bacterial and fungal infections.…”