100% tevredenheidsgarantie Direct beschikbaar na betaling Zowel online als in PDF Je zit nergens aan vast
logo-home
Summary - Clinical immunology (AM_1309) (Vrije Universiteit Amsterdam) €6,99   In winkelwagen

Samenvatting

Summary - Clinical immunology (AM_1309) (Vrije Universiteit Amsterdam)

 8 keer bekeken  0 keer verkocht

Summary - Clinical immunology (AM_1309) (Vrije Universiteit Amsterdam)

Voorbeeld 4 van de 49  pagina's

  • 30 oktober 2024
  • 49
  • 2023/2024
  • Samenvatting
Alle documenten voor dit vak (8)
avatar-seller
laralommers
Clincial immunology
Everything about MS
What is MS?
Definition: Multiple scars in the central nervous system.
Number, size and distribution vary widely  heterogenous disease
Inflammation in the brain and spinal cord
It is an auto-immune disease against myelin, made by the oligodendrocytes.
The pathological hallmarks are: inflammation – demyelination – remyelination – gliosis (scarring)
Inflammation: where immune cells enter the brain via the BBB
Inside out: leakage before immune reaction. Something in the brain causes the infiltration.




Remyelination: there can be a full or partial recovery unless there is gliosis
Degeneration in later disease stages: Atrophy, widening ventricles, both brain and spinal cord




What causes MS?
Is MS an autoimmune disorder or a primary degenerative disorder with secondary inflammatory
demyelination?
Inside out: primary cause of MS is inside the CNS (response to injury paradigm)
Outside in: primary cause of MS is outside the CNS (response to infection paradigm): Epstein Barr
Virus

, MS is caused and/or driven by autoimmunity against CNS components
Healthy persons are tolerant to CNS autoantigens and the tolerance is broken when genetically
susceptible individuals (HLA-DR2 and > 200 other risk alleles with lower impact) are exposed to an
infection (EBV, HERV).
Peripherally-activated immune cells infiltrate the CNS to locally activate a pathophiological
cascade of reactions leading to the demise of axon-myelin units.
What is the epidemiology of MS?
1:1000 get the disease in the Netherlands
Starts between the age of 20-40
Man: woman 1:3
Almost normal life expectancy
What are the risk factors in MS?
Low vitamin D levels
Diet (omega-3)
Smoking
Epstein-Barr virus (everyone needs to have had it if they develop MS):
molecular mimicry: activation of autoreactive cells by cross-reactivity between self-antigens
and foreign agents.
bystander activation: autoreactive cells are activated because of nonspecific inflammatory
events.
MS risk increases 32-fold after EBV infection
Ethnicity
Genetic factors: HLA-DRB1*15 or DR2 haplotype
Microbiome – fecal transfusion
What are the different types of lesions in MS?
A typical MS lesion is ovoid shaped and is in perivascular orientation
Active lesion: immune cells are in the middle of the lesion. T cells (CD8>CD4) and B cells,
predominantly in the meninges and perivascular space.




Chronic lesion: is a slowly growing lesion, where immune cells are on the edge of the lesion.
Mainly involvement of innate immune system.

, Gliosis/scar formation: astrocytes for scar tissue with their extracellular matrix




There are also different types of cortical MS lesions




This cortical pathology is driven by meningeal inflammation in progressive MS.
What are the key players in MS?
T cells
Th1/17 mediated disease (cytokines in plasma/CSF)
T cells can transfer the disease in animal models – outside in hypothesis
Autoreactive T cells recognizing myelin proteins (MOG)
Number of T cells correlate with axonal damage
Functional activity of Tregs reduced in MS
B cells
Clonally expanded B-cells within CSF
Intrathecal production of oligoclonal Ig bands in CSF (diagnostics)
Inflamed CNS favors B-cell homing, survival, and maturation by chemokines and cytokines

, Pathogenic antibodies targeting oligodendrocytes
Follicle like aggregates (germinal center-like structures) in meninges
Microglia
Microglia are the resident macrophages of the CNS
Consist of 10-15% of the cells found in the brain
First line of defense in brain infection and injury
Pro-inflammatory microglia is detrimental and contribute to the destruction of myelin and
neurodegeneration in MS, while anti-inflammatory plays a role in damage repair and remission
What are the clinical symptoms of MS?
Cognitive disturbances: memory, concentration, attention, difficulties organizing.
Pyramidal symptoms: Paresis (verlamming), spasticity, abnormal reflexes.
Sensory symptoms: numbness, tingling/painful sensations, symptom of Lhermitte (pain sensations
by head tilting).
Vision problems: pain behind the eye, decreased color vision, descreased visual acquity (especially
in the central visual fields), diplopia (double vision).
Bladder-/bowel-/sexual problems: incontinence, urine retention (behoud), urinary tract infections,
sexual problems
Coordination problems: ataxia, tremor, balance.
Fatigue: high prevalence, no good treatment, unknown cause, less visible
Less visible: depression, suicide, relationship difficulties
How is MS diagnosed?
Clinical features
Radiological characteristics (MRI)
Abnormalities in cerebrospinal fluid (CSF)
The diagnosis is based on
Dissemination in time (DIT): there need to be multiple time points of relapses
Combination of T2 lesions and contrast-enhancing lesions
DIT can be replaced by CSF measurements where oligoclonal bands indicate MS

Dissemination in space (DIS): there need to be multiple places of the lesions
MS has specific lesion locations: periventricular, cortical, infratentorial (cerebellum), spinal cord
DIS: the lesions need to be in 2 out of the 4 locations.

Clinically isolated syndrome (CIS): monosymptomatic clinical presentation of demyelination, could
evolve into MS.
Radiological isolated syndrome (RIS): monolesion presentation through MRI, could evolve into MS.

The MRI can detect multiple types of lesions
T1 detects irreversible damage as black holes
T2 detects disease burden as white lesions
T1 contrast enhancing lesions detects active lesions

Voordelen van het kopen van samenvattingen bij Stuvia op een rij:

Verzekerd van kwaliteit door reviews

Verzekerd van kwaliteit door reviews

Stuvia-klanten hebben meer dan 700.000 samenvattingen beoordeeld. Zo weet je zeker dat je de beste documenten koopt!

Snel en makkelijk kopen

Snel en makkelijk kopen

Je betaalt supersnel en eenmalig met iDeal, creditcard of Stuvia-tegoed voor de samenvatting. Zonder lidmaatschap.

Focus op de essentie

Focus op de essentie

Samenvattingen worden geschreven voor en door anderen. Daarom zijn de samenvattingen altijd betrouwbaar en actueel. Zo kom je snel tot de kern!

Veelgestelde vragen

Wat krijg ik als ik dit document koop?

Je krijgt een PDF, die direct beschikbaar is na je aankoop. Het gekochte document is altijd, overal en oneindig toegankelijk via je profiel.

Tevredenheidsgarantie: hoe werkt dat?

Onze tevredenheidsgarantie zorgt ervoor dat je altijd een studiedocument vindt dat goed bij je past. Je vult een formulier in en onze klantenservice regelt de rest.

Van wie koop ik deze samenvatting?

Stuvia is een marktplaats, je koop dit document dus niet van ons, maar van verkoper laralommers. Stuvia faciliteert de betaling aan de verkoper.

Zit ik meteen vast aan een abonnement?

Nee, je koopt alleen deze samenvatting voor €6,99. Je zit daarna nergens aan vast.

Is Stuvia te vertrouwen?

4,6 sterren op Google & Trustpilot (+1000 reviews)

Afgelopen 30 dagen zijn er 73918 samenvattingen verkocht

Opgericht in 2010, al 14 jaar dé plek om samenvattingen te kopen

Start met verkopen
€6,99
  • (0)
  Kopen