Neuroimmunology Flashcards
What are the two main ways to disrupt the BBB
1) Infection or inflammatory processes
2) MS
* trauma also can disrupt the BBB, but is less common*
4 things that must happen before autoimmunity occurs
1) autoreactive T/B cells must escape the thymus or bone marrow (site of central tolerance)
2) autoreactive T/B cells must encounter a specific target antigen
3) peripheral tolerance and regulatory mechanisms must fail
4) autoreactive T/B cells must cause damage to the host
How does MHC determine disease susceptibility or resistance in a host?
Certain MHC binds to certain antigens based on the epitopes and anchor residues in the MHC
HLA-B27 - psoriasis since the MHC in these patients binds to skin autoantigens and activates auto T-cells
Why does autoimmunity usually affect women more than men?
Stress hormones and estrogens/androgens increase odds of developing an autoimmunity
- 90% of Sjögren is women
- 90% of SLE is women
General treatments for autoimmunties
NSAIDs
Steroids
Plasmapheresis
Immunotherapies directed to specific cytokines or immune cells
Review of lupus pathology
Some sort of factor promotes the tolerance to breaking down self-antigens
- causes antibodies to form self-binding immune complexes and defective clearance of these immune complexes results in apoptosis bodies
Anti-nuclear antibodies are also formed (called ANAs) by B cells up taking autoimmune complexes (forms self-binding antibodies)
- IFN-a is produced by DCs which increases the autoreactive B-cells life span
Review of MS
Increased movement of Tcells across the BBB due to inflammation (idiopathic cause)
- autoreactive T cells attack myelin sheath and causes degeneration of axons
*known to be linked to chronic EBV infections
Guillain barre syndrome
very Acute inflammation polyneuropathy often preceded via infections of HSV-1, CMV or EBV
- causes damage in myelin in peripheral nerves that slowly works up to the proximal regions
Sjögren syndrome
Most common autoimmune reactions
- almost always females
Produces autoantibodies Anti-Ro/SSA and Anti-La/SSB
- attacks salivary glands and lacrimal glands
Common Symptoms
- dry eyes and dry mouth chronically
- oral thrush
- frequent cavities
- using lissamine green stain in the eyes (shows dead cells)
Rare symptoms:
- peripheral symptoms
- autonomic neuropathy
- trigeminal neurologia
- glossopharyngeal neuropathy (pain in the back of the throat that gets worse with swallowing)
- myelitis (spinal cord inflammation)
NMO
(Neuromyeltis optica)
(Devic’s syndrome)
Syndrome that occurs with inflammation of optic nerve connecting the eyes to the brain
- also inflammation in th spinal cord
Similar symptoms to myelitis except way more Severe weakness, eye pain and weakness and it relapsing
(more severe than myelitis)
- will show presence of NMO-IgG specific antibodies in antibody testing
Acute disseminated encephalomyelitis (ADEM)
Demyelination disease caused secondarily to infections
- MMR
- B-hemolytic strep
- mycoplasma pneumoniae
initiated via autoreactive T-cells and B-cells that cross BBB and react with myelin
(similar to MS except B-cells also get across )
Symptoms: very rapid onset and non progressive
- seizures
- sensory and visual changes* (not associated with general encephalitis)
- confusion
- drowsiness
- general motor defects and weakness
- oculomotor defects
- comas
- if treated, recovers fully
- is associated to rare ADR from MMR vaccines (which is why its most common in children)
Sarcoidosis
Noncaseating granulomas form throughout the body in various organs
almost always has some level of deposition in the lungs and skin
- has a paradoxical effect on immune system*
- increased inflammation but decreased immune response to actual pathogens
Neurosarcoidosis
5% of sarcoidosis cases where the brain is an affected organ
generates a panda sign
(periorbital edema due to lacrimal infiltration)
Symptoms:
- usually cranial nerves are affected so generally Symptoms associated to cranial nerves are seen
- Bell’s palsy
- endocrine changes
Granulomatosis w polyangitis
Wegeners granulomatosis
Associated with autoantibodies
- PR3-ANCA
- c-ANCA
Binds to neutrophil granules and causes auto release of ROS in the neutrophils
- damages endothelial cells leading to vasculitis
Triad of symptoms
1) necrotizing vasculitis
- pain, bloody nasal mucous, oral ulcers and saddle nose
2) necrotizing granulomas of upper airways
- hemoptysis and chronic coughing
3) necrotizing glomerulonephritis
- hematuria and decrease in urine production
Behcet disease
Strongly associated with the presence of HLA-B51
Clinical symptoms
- uveitis (inflammation of middle eye)
- optic neuritis
- strokes and headaches
- menigoencphalitis
- recurrent sterile oral and gentile ulcers (culture negative)
- fever, weight loss
- arthritis
