Autoimmunity versus horror autotoxicus: The struggle for recognition

Silverstein, Arthur M.

doi:10.1038/86280

Cited by 117 publications

(61 citation statements)

References 9 publications

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“…The immune system of type 1 diabetic patients may, however, manifest changes beyond the local islet-destructive effect (46). Our data complete the conflicting experience already existing with vaccination strategies in EAE and human MS (11,21,24). Extreme caution is therefore needed when adopting immunemodulating strategies, taking into consideration that a shift in T-helper differentiation might always represent a transfer of risk from a Th 1 -mediated type IV delayed immune attack to a Th 2 -mediated anaphylactic reaction, especially in situations with an already-activated Th 2 system, such as a coincidental infection or allergy.…”

Section: Discussionmentioning

confidence: 83%

“…However, initial enthusiasm was tempered by the observation that vaccination with self-antigens could elicit anaphylactic shock in the context of a disturbed immune system (11,12). This anaphylactic reaction could be triggered by exactly the same T-cell differentiation shift that provided protection against autoimmunity (21). In contrast to a Th 1 -mediated autoimmune attack, allergic disease is mainly Th 2 dependent (22) and is largely mediated by IgE (22,23).…”

Section: Discussionmentioning

confidence: 99%

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Acute Shock Induced by Antigen Vaccination in NOD Mice

et al. 2003

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Type 1 diabetes in NOD mice can be prevented through autoantigen vaccination by shifting lymphocyte differentiation toward a T-helper 2 (Th 2 ) response. However, in other models of autoimmunity, this approach may be accompanied by unexpected triggering of Th 2 -dependent anaphylactic shock. To test the safety of vaccination therapy in the NOD mouse model, we evaluated the effects of immunization with a wide battery of antigens in NOD, BALB/c, and C57BL/6 mice. Surprisingly, a nondiabetogenic antigen, hen egg white lysozyme, induced severe shock exclusively in NOD mice (shock in 11 of 11 mice, lethal in 3 mice). Shock severity was further increased by a more pronounced Th 2 setting generated by 1␣,25(OH) 2 D 3 administration (17 of 17 mice, lethal in 14 mice, P < 0.0001). Pretreatment with dexamethasone resulted in full rescue, indicating an immune-mediated mechanism. Serum IgE levels and Th 1 /Th 2 cytokine profile analysis showed that the shock phenomenon was paralleled by a Th 2 response. mRNA expression of platelet-activating factor receptor (PAF-R) was significantly higher in NOD mice (P < 0.01) and was further increased by 1␣,25(OH) 2 D 3 . Pretreatment with WEB2086 (PAF-R antagonist) again protected all mice from lethal shock, indicating PAF as an anaphylaxis effector. In conclusion, in NOD mice, vaccination leading to a Th 2 immune shift can result in a lethal anaphylactic reaction. Diabetes 52:335-341, 2003

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Acute Shock Induced by Antigen Vaccination in NOD Mice

et al. 2003

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“…Aberrant patterns of connectivity of the immune system are associated with autoimmune diseases, in which significant changes in the pattern of immu-noglobulin formation occur (41)(42)(43). When von Pirquet and Schick characterized serum sickness , they showed that immunological activities, of themselves, are not always defensive and may be damaging to the organism (47). Soon thereafter, von Pirquet introduced the term allergy to represent this other form of operation of immune mechanisms.…”

Section: The Emergence Of Pathologymentioning

confidence: 99%

The conservative physiology of the immune system

Vaz

Faria

Verdolin

et al. 2003

Braz J Med Biol Res

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Current immunological opinion disdains the necessity to define global interconnections between lymphocytes and regards natural autoantibodies and autoreactive T cells as intrinsically pathogenic. Immunological theories address the recognition of foreignness by independent clones of lymphocytes, not the relations among lymphocytes or between lymphocytes and the organism. However, although extremely variable in cellular/molecular composition, the immune system preserves as invariant a set of essential relations among its components and constantly enacts contacts with the organism of which it is a component. These invariant relations are reflected, for example, in the life-long stability of profiles of reactivity of immunoglobulins formed by normal organisms (natural antibodies). Oral contacts with dietary proteins and the intestinal microbiota also result in steady states that lack the progressive quality of secondary-type reactivity. Autoreactivity (natural autoantibody and autoreactive T cell formation) is also stable and lacks the progressive quality of clonal expansion. Specific immune responses, currently regarded as the fundament of the operation of the immune system, may actually result from transient interruptions in this stable connectivity among lymphocytes. More permanent deficits in interconnectivity result in oligoclonal expansions of T lymphocytes, as seen in Omenn s syndrome and in the experimental transplantation of a suboptimal diversity of syngeneic T cells to immunodeficient hosts, which also have pathogenic consequences. Contrary to theories that forbid autoreactivity as potentially pathogenic, the physiology of the immune system is conservative and autoreactive. Pathology derives from failures of these conservative mechanisms.

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“…Autoimmunity has been the target of an increasing amount of interest in recent decades [1,2]. In part, this is because more diseases have been recognized to be the consequence of reactivity of the autologous immune system against self tissues.…”

Section: Introductionmentioning

confidence: 99%

Do autoantigens define autoimmunity or vice versa?

Eisenberg

2005

Eur J Immunol

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The basic function of the adaptive immune system is to distinguish self from foreign. The failure of self tolerance can result in autoimmunity, which comes in many forms but still targets a limited selection of the total available autologous determinants. This selectivity must reflect the underlying mechanisms of the autoimmune reaction, as well as the particular features of the autoantigens that are targeted. Here I discuss the overall paradigm of autoimmunity, and what kinds of mechanisms might play a role. It is likely that multiple different pathways are critical in various diseases, and even in a single condition.

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Autoimmunity versus horror autotoxicus: The struggle for recognition

Cited by 117 publications

References 9 publications

Acute Shock Induced by Antigen Vaccination in NOD Mice

Acute Shock Induced by Antigen Vaccination in NOD Mice

The conservative physiology of the immune system

Do autoantigens define autoimmunity or vice versa?

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