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Can the immune system be harnessed to repair the CNS?

Abstract

Experimental and clinical data have demonstrated that activating the immune system in the CNS can be destructive. However, other studies have shown that enhancing an immune response can be therapeutic, and several clinical trials have been initiated with the aim of boosting immune responses in the CNS of individuals with spinal cord injury, multiple sclerosis and Alzheimer's disease. Here, we evaluate the controversies in the field and discuss the remaining scientific challenges that are associated with enhancing immune function in the CNS to treat neurological diseases.

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Figure 1: The magnitude and rate of tissue pathology influences the nature of neuroimmune interactions.

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Correspondence to Phillip G. Popovich.

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DATABASES

OMIM

Alzheimer's disease

multiple sclerosis

Parkinson's disease

FURTHER INFORMATION

List of completed and ongoing stroke trials

Additional information on the humanized Aβ antibody, AAB-001 (bapineusumab)

Center for Brain and Spinal Cord Repair

Glossary

Adaptive immunity

The response of T and B cells to antigens as a result of infection, injury or intentional immunization. It enables discrimination between self and non-self antigens and the ability to respond more rapidly and efficiently to antigens upon subsequent re-exposure.

Adjuvant

A substance, usually an oil, aluminium salt or virosome that amplifies the immune response to an antigen that is injected as part of a vaccine.

Antibodies

Glycoproteins produced by B lymphocytes that are a critical component of adaptive immunity.

Antigen

An antibody generating molecule that elicits adaptive immunity. It is typically a protein that is processed and presented as part of a complex with MHC molecules to T lymphocytes.

B lymphocyte

Adaptive immune cell that acts as an antigen presenting cell and produces antibodies against protein and glycoprotein antigens.

Bystander suppression

The generation of antigen-specific regulatory T cells by oral or nasal administration of low doses of antigen. After these regulatory T cells encounter the autoantigen in the target organ, they release cytokines (for example, IL-10 and TGF-β) that suppress deleterious immune functions.

Chemokines

A family of small (8–10 kD) chemotactic cytokines that promote directed migration in responsive cells.

Complement proteins

A family of serum proteins that promote opsonization, chemotaxis and cell lysis. They are part of the innate immune system and can be produced in the CNS by glia and neurons.

Cytokines

Originally defined as immune system proteins that modified biological responses, these proteins are now known to be released by most cells and are important in regulating intercellular communication, cell function and cell survival.

Fibrosis

Development of excess fibrous connective tissue, usually as a result of injury or infection. It promotes scar formation during wound healing.

Immune response

Activation of the innate and/or adaptive immune system in response to a disruption of tissue (or systemic) homeostasis.

Inflammation

The complex biological response of vascularized tissues to injury or infection. Derived from the Latin, inflammare (to set on fire), it was historically defined by the clinical signs of pain, redness, heat, swelling and loss of function.

Innate immunity

A phylogenetically ancient mechanism of defence against pathogens that is comprised of physical and chemical barriers and inducible cells (including monocytes, neutrophils and dendritic cells) or proteins. Unlike the adaptive immune system, it does not require exposure to antigen to become active.

Leukocyte

White blood cell derived from multipotent haematopoetic stem cells in the bone marrow. Leukocytes are of myeloid or lymphoid lineage and are found in the blood and lymphatic system.

Major histocompatability complex (MHC) molecule

Membrane glycoprotein that is essential for recognition of self and non-self antigens by adaptive immune cells.

Monocyte

Circulating precursor of tissue macrophages, an innate immune cell.

T lymphocyte

A leukocyte involved in triggering, amplifying and regulating immune responses against specific antigens presented by B cells, macrophages (microglia in CNS) or dendritic cells.

Toll-like receptors

(TLRs). Non-catalytic receptors that recognize structurally conserved molecules found on microbes and non-pathogenic molecules found at sites of tissue injury. TLRs are involved in the activation of innate immune cells.

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Popovich, P., Longbrake, E. Can the immune system be harnessed to repair the CNS?. Nat Rev Neurosci 9, 481–493 (2008). https://doi.org/10.1038/nrn2398

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