Innate and Adaptive Immunity for the Pathobiology of Parkinson's Disease

Abstract

Innate and adaptive immunity affect the pathogenesis of Parkinson’s disease (PD). In particular, activation of microglia influences degeneration of dopaminergic neurons during disease. Cell-to-cell interactions and immune regulation critical for neuronal homeostasis are also influenced immune responses. The links between T cell immunity and nigrostriatal degeneration are supported by laboratory, animal model, and human pathologic investigations. Immune associated biomarkers in spinal fluids and brain tissue of patients with idiopathic or familial forms of PD provide means to improve diagnosis and therapeutic monitoring for disease. Relationships between oxidative stress, inflammation, and immune-mediated cell death pathways are examined in this review as they are linked to PD pathogenesis. Harnessing the immune system by drugs or by vaccination remain promising future therapeutic options.

The age-related deficit in LTP is associated with changes in perfusion and blood-brain barrier permeability

“…Despite this, infiltration of circulating cells has been shown to occur when BBB permeability is increased. Thus T cell infiltration has been found in CNS tissues of patients with Parkinson's disease (Stone et al, 2009) and Alzheimer's disease (Schindowski et al, 2007;Togo et al, 2002) and infiltration of cells has also been reported following ischemic insult and with age (Popescu et al, 2009) and bacterial and viral infections (Stamatovic et al, 2008). In this study, increased BBB permeability was associated with increased expression of IP-10 and MCP-1.…”

“…The evidence suggests that there is minimal infiltration of peripheral cells in the healthy brain; this is probably primarily due to the fact that expression of chemotactic agents is low, because migration of cells appears to be controlled mainly by expression of chemokines and adhesion molecules and their receptors. However, there is a marked increase in cell infiltration following trauma (Shichita et al, 2009) and in neurodegenerative conditions (Stone et al, 2009;Togo et al, 2002) when the blood-brain barrier (BBB) is breached and when expression of chemotactic agents is increased.…”

Alpha-Synuclein and the Immune Response in Parkinson’s Disease

“…This neuroprotective effect was later found to be mediated by the CD4 + type of T cells, suggesting the possible involvement of Treg cells (Laurie et al, 2007). Later work by the same group confirmed this hypothesis by showing that passive transfer to MPTP mice of activated Treg cells, but not effector T cells, efficiently suppressed microglial activation and afforded neuroprotection (Reynolds et al, 2007), suggesting that the immunomodulating abilities of Treg cells could potentially be utilized as a therapeutic approach against PD (Stone et al, 2009). …”

“…M1 vs. M2), is still unknown (Appel et al, 2010). But overall, the communication established between microglia, T cells and neurons seem to indicate that the immune response is not only a consequence of injury, but that it actively contributes to the balance between neuroprotection and neurotoxicity (Appel et al, 2010;Stone et al, 2009). To analyse the possibility that humoral immunity may play a role in initiating or regulating inflammation, Orr et al (Orr et al, 2005) analysed the association between nigral degeneration and humoral immune markers in brain tissue of patients with idiopathic or genetic PD and controls.…”

Inflammation in Parkinson’s Disease: Causes and Consequences

“…Increased levels of CD4 + have been reported in the serum of patients with PD, suggesting peripheral activation of lymphocytes (Bas et al, 2001;Fiszer et al, 1994;). Infiltrating cytotoxic CD4 + and CD8 + T cells, but not B cells, have been observed in the inflamed SNpc of post-mortem PD human specimens and in the MPTP-induced mouse model of PD during the course of neurodegeneration (Brochard et al, 2009;Ferrari & Tarelli, 2011;Stone et al, 2009). In support of a role for systemic immune cells in the degeneration of nigral DA neurons, CD4 -/-mice have been shown to be resistant to MPTP-induced neurotoxicity in the SN (Brochard et al, 2009).…”