Neuroimmunology is a combination of various fields of science, namely, fundamental biology, neurology, immunology, virology, pathology, chemistry, and psychiatry of the central nervous system (CNS).
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Scientists associated with neuroimmunology study the interactions of the immune system with the nervous system during homeostasis and response to injuries. The main objective of this branch of science is to develop strategies to prevent or treat neuroimmunological diseases.
Central nervous system and immune system
The central nervous system comprises the brain and the spinal cord. The brain controls all the functions of the body, whereas, the spinal cord contains the network that transports information to and from the brain. Various nerves branch out of the spinal cord and these nerves constitute the peripheral nervous system.
The central nervous system and other nerves present in the body are covered by myelin, which is a fatty protective sheath. The myelin allows the passage of electrical impulses from the brain, down the spinal cord, to give signals to the muscles.
The immune system protects the body from harmful foreign invaders. Immune cells are produced in the bone marrow, spleen, and thymus gland. One of the most important types of immune cells is leucocytes. These are white blood cells that can travel around the body through lymph nodes and blood vessels.
The main functions of this cell include seeking and destroying harmful invaders. Leucocytes are further classified into two types, namely, phagocytes and lymphocytes. A phagocytic cell (e.g., neutrophils) engulfs or eats invading organisms. Lymphocytes are a type of white blood cell that includes natural killer cells, B cells, and T cells.
Lymphocytes remember previous foreign invaders, such that the immune system easily recognizes and destroys these harmful invaders on their next attack. The B cells produce antibodies against invading bacteria, viruses, and toxins. The B cells also seek out the invaders and the T cells are associated with eliminating them.
Communication between the immune system and central nervous system
Previously, it was believed that the immune system was autonomous and the brain was protected by the blood-brain barrier (BBB). However, in the past decade researchers provided robust evidence that challenged this notion. The immune system's reach within the CNS is extensive.
Previous studies have shown that the nervous system not only receives messages from the immune system but the messages from the brain regulate immune functions that subsequently control inflammation in other tissues.
Research on the interaction between the immune system and the CNS revealed that several molecules associated with the immune system are extensively expressed and functional in the nervous system and vice versa. Communication between microglia and neurons was found to be essential for maintaining homeostasis. Researchers also reported the occurrence of cross-talk between oligodendrocytes and microglia.
Studies on the communication between the immune system and the CNS using mice models revealed that disturbances occur, such as the interactions during peripheral infections that trigger microglial activation and enhance neuron degradation. Another study revealed maternal infections may lead to long‐term changes in microglia and abnormal brain development in the newborn baby.
Neuroimmunological disorders
Neuroimmunology is a study of neurological conditions that are caused by the malfunctioning of the immune system. In this case, the immune system attacks the own body instead of protecting itself from foreign invaders. Some of the examples of neuroimmunological disorders are acute disseminated encephalomyelitis, multiple sclerosis, neuromyelitis optica, and transverse myelitis.
Generally, diagnosis of such diseases includes clinical assessment and proper diagnostic testing (e.g., neuro-imaging, neurophysiologic testing, cerebrospinal fluid assessment, etc.). As stated above, one of the neuroimmunological diseases is multiple sclerosis. In this disease, the T lymphocytes along with other inflammatory mediators, damage the protective myelin sheath.
Researchers believe malfunctioning of the immune system may take part in the initiation and the pathogenesis of neurodegenerative diseases, neurodevelopmental disorders (e.g., autism), and mental health disorders (e.g., schizophrenia). Neuroimmunological disorders occur due to various conditions such as the pruning of neuronal synapses, effects of CNS development in utero, and inflammation.
Future of neuroimmunology research
Scientists believe advancements in biomarker research would aid in the rapid diagnosis of neuroimmunological diseases. Additionally, it will also help in the efficient monitoring of the disease course and response to therapy in clinical trials. Some of the biomarkers of neuroimmunological diseases include markers of BBB disruption, oxidative stress, demyelination, axonal/neuronal damage, gliosis, remyelination, and repair.
Additionally, researchers also focus on markers of altered immune functions like chemokines, cytokines, antibodies, antigen presentation, and changes in cellular subpopulations.
The advancements in neuroimmunological research also depend on disease modeling. Some of the technological advancements, such as the CRISPR/cas9 system allow accurate genomic engineering, which is extremely essential for the rapid development of transgenic animal models, producing single‐gene mutations in adult animals. CRISPR/cas9 or other similar systems can increase transgene efficiency by regulating gene expression using inducible expression systems. Also, the use of induced pluripotent stem cells (iPSCs) from patients will enable the model to efficiently translate fundamental research data.
Scientists explained the importance of next‐generation sequencing in neuroimmunological diseases. Next‐generation sequencing helps in the identification of genetic variants in neuroimmunological diseases. Data obtained using this technology contribute to the development of pharmacogenomics and personalized medicine and designing algorithms.
Neuroimmunology and long-coronavirus disease
Several individuals are suffering from a long-coronavirus disease (long-COVID) which is associated with the persistence of coronavirus disease symptoms for a prolonged period. Some of the symptoms that are commonly found in patients undergoing long-COVID are profound fatigue, muscle pains, neurocognitive difficulties, weakness, and depression.
Researchers have studied many of these symptoms during previous psychoneuroimmunology research. Thereby, they believe existing neuroimmunology studies could aid in better understanding of these symptoms during long-COVID. These studies could also help in the development of strategies to treat people suffering from long-COVID.
Sources:
- Mondelli, V. and Pariante, M.C. (2021). What can neuroimmunology teach us about the symptoms of long-COVID? Oxford Open Immunology, 2(1), pp. iqab004, https://doi.org/10.1093/oxfimm/iqab004
- What is Neuroimmunology? NHS Foundation Trust. (2020). [Online] Available at: www.gosh.nhs.uk/.../
- Nutma, E., Willison, H., Martino, G., and Amor. S. (2019). Neuroimmunology - the past, present, and future. Clinical and experimental immunology, 197(3), 278–293. https://doi.org/10.1111/cei.13279
Further Reading