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The Peripheral Immune Response to Stroke

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Non-Neuronal Mechanisms of Brain Damage and Repair After Stroke

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

Abstract

Historically, the central nervous system (CNS) has been viewed as a place with limited immune surveillance and capacity to mount immune responses. This has led to attribute “immunological privilege” to the CNS, a term first coined by Billingham and Boswell [1]. Already in the nineteenth century the Dutch ophthalmologist van Dooremaal [2] described the phenomenon of immune privilege by demonstrating the long-term survival of mouse skin grafts placed in the anterior chamber of a dog’s eye. However, within the brain, immune privilege does not apply to all structures. Murphy and Sturm [3] observed that allogeneic tumor transplants were readily rejected when they came in contact with the cerebral ventricles while transplants that were embedded within the brain parenchyma did not elicit an immune response and showed prolonged survival times. These studies were later extended by Medawar [4] to show that allogeneic skin grafts transplanted into the anterior chamber of the eye or the brain of rabbits were efficiently rejected when the host was previously immunized with donor-derived cells and that this rejection was dependent on vascularization of the graft. The resistance of the CNS to mount an effective immune response also extends to the innate immune system. Bacterial endotoxin injected into the brain parenchyma triggers less inflammatory response as measured by immune cell infiltration, than injection of the same endotoxin dose into the skin [5]. Similar to observations with the adaptive immune response, the reduction in endotoxin-mediated inflammation was not found when endotoxin was injected into the ventricles. These studies collectively suggest that the CNS is not immune privileged per se, but there are mechanisms in place to suppress both the innate and adaptive immune responses. These include the blood–brain barrier (BBB) and the glia limitans, which minimize the exchange of potentially antigenic macromolecules and pro-inflammatory mediators (e.g., cytokines, chemokines, DAMP) and pose a barrier for easy immune cell entry from the circulation. In addition, the brain features a generally anti-inflammatory milieu under homeostatic conditions sustained by the expression by highly immunosuppressive cytokines such as transforming growth factor-β (TGF-β) and insulin-like growth factor-1 (IGF-1). Once these structural and molecular barriers are removed, as it is the case during ischemic brain injury, inflammation can proceed “as planned” and contribute to the outcome of stroke. This chapter will briefly discuss immune cells participating in the response to cerebral ischemia, deliberate potential entry points of these cells to gain access to the ischemic tissue, and outline the role of the ischemic brain in shaping the peripheral immune response.

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Authors and Affiliations

  1. Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, 407 East 61st Street, RR 409, New York, NY, 10065, USA

    Josef Anrather

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  1. Josef Anrather
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Correspondence to Josef Anrather .

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  1. Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Jun Chen

  2. Pittsburgh Institute of Brain Disorders and Recovery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    John H. Zhang

  3. Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, California, USA

    Xiaoming Hu

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Anrather, J. (2016). The Peripheral Immune Response to Stroke. In: Chen, J., Zhang, J., Hu, X. (eds) Non-Neuronal Mechanisms of Brain Damage and Repair After Stroke. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-319-32337-4_9

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  • DOI: https://doi.org/10.1007/978-3-319-32337-4_9

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