Lecture 14 - The Nervous System Flashcards
What are the differences between myelin sheaths in the CNS and PNS?
- PNS myelin is formed from Schwann cells and CNS myelin is formed from oligodendrocytes
- For the CNS, oligodendrocytes can coil around 60 fibres simultaneously, and the sheaths they form lack a neurilemma
- The neurilemma remains mostly intact when neurons are damaged, and plays a large role in fibre regeneration, which is essentially abscent in the CNS
What antigens are associated with Multiple Sclerosis (MS)?
- Myelin basic protein (MBP),
- Proteolipid protein (PLP),
- Myelin oligodendrocyte glycoprotein (MOG)
What is Experimental autoimmune encephalomyelitis (EAE) and how does it relate to MS?
• Mice injected with Myelin developed a similar neurological disease (Experimental autoimmune encephalomyelitis)
• The antigen that induced EAE were: Myelin basic protein (MBP), Proteolipid
protein (PLP), Myelin oligodendrocyte glycoprotein (MOG)
• Antigen specific T cells from EAE affected mice were injected to health mice
which then developed EAE (adoptive transfer: transfer of T cells specific for these myelin antigen induced the disease)
• T cells specific for these antigen have been found in blood and CSF of patients
with MS
Describe the T cells response in MS.
• CD4 T cells ( TH1 and TH17) react against Myelin Antigens
- Release of IFN-ɣ, IL-17
- Activated TH1 cells secreting IFN-ɣ, activate macrophages, which secrete proteases and cytokines
- IL-17 stimulates macrophages, inflammation (however no neutrophil infiltrate seen in MS)
What are the two models used to explain the activation of MS?
- Primary activation by intrinsic antigens
* Primary activation by extrinsic antigens
What are the two forms of Guillian Barre syndrome (GBS)?
- Acute Inflammatory Demyelinating Polyneuropathy (AIDP)
* Acute Motor Axonal Neuropathy (AMAN)
Describe the immunopathology of the two forms of GBS.
• Acute Inflammatory Demyelinating Polyneuropathy (AIDP)
– Demyelinating form of GBS features damage to the myelin sheath by T cells and macrophages (antibodies involved – complement – opsonisation)
• Acute Motor Axonal Neuropathy (AMAN)
– Axonal form is mediated IgG antibodies directed against the cell membrane covering the axon (nodes of Ranvier) – complement activation
What organism is often associated with GBS and how is involved?
– Campylobacter jejuni has been associated with 30% of cases
• Infections with pathogens, such as Campylobacter jejuni, can trigger humoral
immune responses.
• Lipo-oligosaccharides on the C. jejuni outer membrane may elicit the production of antibodies that cross-react with gangliosides, such as GM1 and GD1a on peripheral nerves.
In schizophrenia antibodies are produced to brain and other structures. Give two explanations of how these antibodies come about.
• Studies suggest schizophrenic patient have a reduced risk for cancer (they could be producing antibodies against some types of cancer)
– Abs to heat shock protein and ICAM do correlate
What role could cytokines play in schizophrenia development?
• Schizophrenia patients have increase levels of pro-inflammatory cytokines
– IL-1, IL-6, TNF in blood and CSF
– Also increase in IL-4 indicating a shift to Th2 response
– There is a suggestion that pro-inflammatory cytokines in response to an infection or other stress during neurodevelopment may result in aberrations in neurodevelopment
– Genetic alterations in cytokine genes may contribute
– These may just predispose to developing schizophrenia and a later episode (injury,
stress, illness…) results in disease
What is the most consistent immunological abnormality found in Mood disorders?
– Reduced NK cell function is one of the most consistent immunological finding in
depression
How are neurotransmitters and the immune system linked in mood disorders?
– Enhanced noradrenalin results in increase glucocorticoids which inhibits immune response
– Patients with depression have reduced expression of glucocorticoid receptors
– Negative feed back to immune system impaired
– Cytokine overproduction
– Macrophages produce tetrahydrobiopterin (THB) requires for serotonin synthesis
– Cytokines influence macrophage production of THB
Autism has been suggested to an autoimmune disorder. What mechanisms could be causing the Autism?
• Immune alterations
– T cell mediated immune deficiency
– Increased activated T cells
– Increase in monocytes
– Increase immunoglobulin levels
– Shift to Th2 type response (reduced IL-2 and INF-ɣ, increase in IL-4)
– Increase in pro-inflammatory cytokines (TNF, IL-1, IL-6)
– Features of autoimmune disorder associated with viral infection
– Increase prevalence of family members with autoimmune disease
– Higher frequency of antibodies to brain antigens (Myelin basic protein, neurofilament protein)
. Describe two possible immune mechanisms that could result in Alzheimer’s disease.
• Inflammation and free radical induced oxidative stress
– Microglial cells phagocytose and degrade Amyloid β
– Decreased Amyloid β catabolism results in phagocytosis by microglial cell
– Stimulated of microglial cells then produce free radicals (NO) and inflammatory cytokines
– IL-1, IL-6 and TNF inflammatory but also cause Amyloid β production
– TNF appears to be most important: in one study anti-TNF injected into brain stops /reduces effects
• Herpes infection
– Suggested a peripheral infection leads to entry of cytokines into brain
– Causes reactivation of HSV-1 leading to inflammation / immune mechanisms resulting in neuronal damage
